Patient and anesthesia characteristics of children with low pre-incision blood pressure: A retrospective observational study

Background: Intraoperative blood pressure has been suggested as a key factor for safe pediatric anesthesia. However, there is not much insight into factors that discriminate between children with low and normal pre-incision blood pressure. Our aim was to explore whether children who have a low blood pressure during anesthesia are different than those with normal blood pressure. The focus of the present study was on the pre-incision period. Methods: This retrospective study included pediatric patients undergoing anesthesia for non-cardiac surgery at a tertiary pediatric university hospital, between 2012 and 2016. We analyzed the association between pre-incision blood pressure and patient- and anesthesia characteristics, comparing low with normal pre-incision blood pressure. This association was further explored with a multivariable linear regression. Results: In total, 20 962 anesthetic cases were included. Pre-incision blood pressure was associated with age (beta −0.04 SD per year), gender (female −0.11), previous surgery (−0.15), preoperative blood pressure (+0.01 per mm Hg), epilepsy (0.12), bronchial hyperactivity (−0.18), emergency surgery (0.10), loco-regional technique (−0.48), artificial airway device (supraglottic airway device instead of tube 0.07), and sevoflurane concentration (0.03 per sevoflurane %). Conclusions: Children with low pre-incision blood pressure do not differ on clinically relevant factors from children with normal blood pressure. Although the present explorative study shows that pre-incision blood pressure is partly dependent on patient characteristics and partly dependent on anesthetic technique, other unmeasured variables might play a more important role

Non-symmetric approach to single-screw expander and compressor modeling

Single-screw type volumetric machines are employed both as compressors in refrigeration systems and, more recently, as expanders in organic Rankine cycle (ORC) applications. The single-screw machine is characterized by having a central grooved rotor and two mating toothed starwheels that isolate the working chambers. One of the main features of such machine is related to the simultaneous occurrence of the compression or expansion processes on both sides of the main rotor which results in a more balanced loading on the main shaft bearings with respect to twin-screw machines. However, the meshing between starwheels and main rotor is a critical aspect as it heavily affects the volumetric performance of the machine. To allow flow interactions between the two sides of the rotor, a non-symmetric modelling approach has been established to obtain a more comprehensive model of the single-screw machine. The resulting mechanistic model includes in-chamber governing equations, leakage flow models, heat transfer mechanisms, viscous and mechanical losses. Forces and moments balances are used to estimate the loads on the main shaft bearings as well as on the starwheel bearings. An 11 kWe single-screw expander (SSE) adapted from an air compressor operating with R245fa as working fluid is used to validate the model. A total of 60 steady-steady points at four different rotational speeds have been collected to characterize the performance of the machine. The maximum electrical power output and overall isentropic efficiency measured were 7.31 kW and 51.91%, respectively

Altered bile acid kinetics contribute to postprandial hypoglycaemia after Roux-en-Y gastric bypass surgery

Background/objectives: Bile acids (BA) act as detergents in intestinal fat absorption and as modulators of metabolic processes via activation of receptors such as FXR and TGR5. Elevated plasma BA as well as increased intestinal BA signalling to promote GLP-1 release have been implicated in beneficial health effects of Roux-en-Y gastric bypass surgery (RYGB). Whether BA also contribute to the postprandial hypoglycaemia that is frequently observed post-RYGB is unknown. Methods: Plasma BA, fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), GLP-1, insulin and glucose levels were determined during 3.5 h mixed-meal tolerance tests (MMTT) in subjects after RYGB, either with (RYGB, n = 11) or without a functioning gallbladder due to cholecystectomy (RYGB-CC, n = 11). Basal values were compared to those of age, BMI and sex-matched obese controls without RYGB (n = 22). Results: Fasting BA as well as FGF19 levels were elevated in RYGB and RYGB-CC subjects compared to non-bariatric controls, without significant differences between RYGB and RYGB-CC. Postprandial hypoglycaemia was observed in 8/11 RYGB-CC and only in 3/11 RYGB. Subjects who developed hypoglycaemia showed higher postprandial BA levels coinciding with augmented GLP-1 and insulin responses during the MMTT. The nadir of plasma glucose concentrations after meals showed a negative relationship with postprandial BA peaks. Plasma C4 was lower during MMTT in subjects experiencing hypoglycaemia, indicating lower hepatic BA synthesis. Computer simulations revealed that altered intestinal transit underlies the occurrence of exaggerated postprandial BA responses in hypoglycaemic subjects. Conclusion: Altered BA kinetics upon ingestion of a meal, as frequently observed in RYGB-CC subjects, appear to contribute to postprandial hypoglycaemia by stimulating intestinal GLP-1 release

The Dutch multidisciplinary guideline osteoporosis and fracture prevention, taking a local guideline to the international arena

Background: In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions. Methods: A multidisciplinary working group was formed with delegates from Dutch scientific and professional societies, including representatives from the patient’s organization and the Dutch Institute for Medical Knowledge. The purpose was to obtain a broad consensus among all participating societies to facilitate the implementation of the updated guideline. Results: Novel recommendations in our guideline are as follows: - In patients with an indication for DXA of the lumbar spine and hips, there is also an indication for VFA. - Directly starting with anabolic drugs (teriparatide or romosozumab) in patients with a very high fracture risk; - Directly starting with zoledronic acid in patients 75 years and over with a hip fracture (independent of DXA); - Directly starting with parenteral drugs (denosumab, teriparatide, zoledronic acid) in glucocorticoid-induced osteoporosis with very high fracture risk; - A lifelong fracture risk management, including lifestyle, is indicated from the start of the first treatment. Conclusion: In our new multidisciplinary guideline osteoporosis and fracture prevention, we developed 5 “relatively new statements” that are all a crucial step forward in the optimization of diagnosis and treatment for fracture prevention. We also developed 5 flowcharts, and we suppose that this may be helpful for individual doctors and their patients in daily practice and may facilitate implementation.</p

Beheersing Botrytis in potplanten (pilotgewas: cyclaam)

Botrytis leidt in potplanten nog steeds tot veel uitval. Chemische bestrijding werkt onvoldoende. Doel van dit onderzoek was om de effectiviteit te toetsen van niet-chemische en chemische producten op versterking van de natuurlijke plantafweersystemen en preventieve werking onder praktijkcondities. Omdat beheersing van vochtcondities in het klimaat een belangrijke rol speelt bij Botrytis zijn daarnaast verschillende combinaties getoetst van producten (substraat, afdekmateriaal, open potrand) om het vochtgehalte op en in de potgrond optimaal te verlagen

Kaposiform hemangioendothelioma and tufted angioma – (epi)genetic analysis including genome-wide methylation profiling

Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular condition of childhood and is dinicopathologically related to tufted angioma (TA), a benign skin lesion. Due to their rarity molecular data are scarce. We investigated 7 KHE and 3 TA by comprehensive mutational analysis and genome-wide methylation profiling and compared the clustering, also with vascular malformations. Lesions were from 7 females and 3 males. The age range was 2 months to 9 years with a median of 10 months. KHEs arose in the soft tissue of the thigh (n = 2), retroperitoneum (n = 1), thoracal/abdominal (n = 1), supraclavicular (n = 1) and neck (n = 1). One patient presented with multiple lesions without further information. Two patients developed a Kasabach-Merritt phenomenon. TAs originated in the skin of the shoulder (n = 2) and nose/forehead (n = 1). Of the 5 KHEs and 2 TAs investigated by DNA sequencing, one TA showed a hot spot mutation in NRAS, and one KHE a mutation in RAD50. Unsupervised hierarchical clustering analysis indicated a common methylation pattern of KHEs and TAs, which separated from the homogeneous methylation pattern of vascular malformations. In conclusion, methylation profiling provides further evidence for KHEs and TAs potentially forming a spectrum of one entity. Using next generation sequencing, heterogeneous mutations were found in a subset of cases (2/7) without the presence of GNA14 mutations, previously reported in KHE and TA

Clues For Genetic Anticipation In Multiple Endocrine Neoplasia Type 1

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease caused by the loss of function of the MEN1 gene, a tumor-suppressor gene that encodes the protein menin. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine tumors (dpNET), pituitary tumors (PIT), adrenal adenomas, and bronchopulmonary (bp-NET), thymic, and gastric neuroendocrine tumors. More insight into factors influencing the age-related penetrance of MEN1 manifestations could provide clues for more personalized screening programs. OBJECTIVE: To investigate whether genetic anticipation plays a role in the largest known MEN1 families in the Netherlands. METHODS: All Dutch MEN1 families with ≥ 10 affected members in ≥ 2 successive generations were identified. Age at detection of the different MEN1-related manifestations were compared among generations using regression analyses adjusted for competing risks. To correct for the beneficial effect of being under surveillance, manifestations occurring during surveillance were also separately compared. RESULTS: A total of 152 MEN1 patients from 10 families were included. A significantly decreased age at detection of pHPT, dpNET, PIT, and bp-NET was found in successive generations (P < 0.0001). Adjusted analyses led to the same results. CONCLUSIONS: These results suggest the presence of genetic anticipation. However, due to a risk of residual bias, the results must be interpreted with caution. After independent validation in other cohorts and further translational research investigating the molecular mechanisms explaining this phenomenon in MEN1, the results might add to future, more personalized, screening protocols and earlier screening for future generations of MEN1 patients

Dissecting protein-induced DNA looping dynamics in real time

Many proteins that interact with DNA perform or enhance their specific functions by binding simultaneously to multiple target sites, thereby inducing a loop in the DNA. The dynamics and energies involved in this loop formation influence the reaction mechanism. Tethered particle motion has proven a powerful technique to study in real time protein-induced DNA looping dynamics while minimally perturbing the DNA–protein interactions. In addition, it permits many single-molecule experiments to be performed in parallel. Using as a model system the tetrameric Type II restriction enzyme SfiI, that binds two copies of its recognition site, we show here that we can determine the DNA–protein association and dissociation steps as well as the actual process of protein-induced loop capture and release on a single DNA molecule. The result of these experiments is a quantitative reaction scheme for DNA looping by SfiI that is rigorously compared to detailed biochemical studies of SfiI looping dynamics. We also present novel methods for data analysis and compare and discuss these with existing methods. The general applicability of the introduced techniques will further enhance tethered particle motion as a tool to follow DNA–protein dynamics in real time

Personalized neck irradiation guided by sentinel lymph node biopsy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx with a clinically negative neck:(Chemo)radiotherapy to the PRIMary tumor only. Protocol of the PRIMO study

Background: Elective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life. Methods/design: This is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment. Discussion: If this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care.</p