Metopic synostosis patients are at risk for neurodevelopmental disorders despite a negligible risk of intracranial hypertension. To gain insight into the underlying pathophysiology of metopic ...synostosis and associated neurodevelopmental disorders, we aimed to investigate brain volumes of non-syndromic metopic synostosis patients using preoperative MRI brain scans. MRI brain scans were processed with HyperDenseNet to calculate total intracranial volume (TIV), total brain volume (TBV), total grey matter volume (TGMV), total white matter volume (TWMV) and total cerebrospinal fluid volume (TCBFV). We compared global brain volumes of patients with controls corrected for age and sex using linear regression. Lobe-specific grey matter volumes were assessed in secondary analyses. We included 45 metopic synostosis patients and 14 controls (median age at MRI 0.56 years IQR 0.36 and 1.1 years IQR 0.47, respectively). We found no significant differences in TIV, TBV, TGMV or TCBFV in patients compared to controls. TWMV was significantly smaller in patients (-62,233 mm
95% CI = -96,968; -27,498, Holm-corrected p = 0.004), and raw data show an accelerated growth pattern of white matter in metopic synostosis patients. Grey matter volume analyses per lobe indicated increased cingulate (1378 mm
95% CI = 402; 2355) and temporal grey matter (4747 95% CI = 178; 9317) volumes in patients compared to controls. To conclude, we found smaller TWMV with an accelerated white matter growth pattern in metopic synostosis patients, similar to white matter growth patterns seen in autism. TIV, TBV, TGMV and TCBFV were comparable in patients and controls. Secondary analyses suggest larger cingulate and temporal lobe volumes. These findings suggest a generalized intrinsic brain anomaly in the pathophysiology of neurodevelopmental disorders associated with metopic synostosis.
Do physicians apply an early-switch strategy (from intravenous to oral antibiotics) in clinically stable patients hospitalised with community-acquired pneumonia (CAP)? If not, why not? In a ...multicentre prospective cohort study, adult patients admitted for i.v. CAP treatment were included. On day 3 of antibiotic treatment, clinical stability was assessed and treating resident physicians were interviewed on their switch strategies. Additionally, treating physicians were interviewed to evaluate their knowledge of and adherence to guideline advice. 149 (92%) out of 162 patients were included and 97 (91%) out of 107 physicians were interviewed. A switch to oral antibiotics was possible in 68 (46%) out of 149 patients on day 3 of treatment but not performed in 27 (40%) out of 68. Patient factors delaying the switch were high CURB-65 (confusion of new onset, urea >7 mmol · L(-1), respiratory rate of ≥ 30 breaths · min(-1), blood pressure <90 mmHg or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 yrs) score (on admission) (p=0.04) and oxygen treatment (p=0.04), high temperature (p=0.00) and high respiration rate (p=0.04) (day 3). Physicians' barriers to an early switch in clinically stable patients included misconceptions (26 (55%) out of 47), practical considerations (13 (28%) out of 47) and organisational factors (eight (17%) out of 47). Strikingly, 91 (94%) out of 97 interviewed physicians were not aware of guideline advice. The switch from i.v. to oral antibiotics is often unnecessarily delayed in patients hospitalised with CAP due to different types of barriers.
Summary
Regulatory T cells Tregs; CD4+CD25+ forkhead box protein 3 (FoxP3+) are subsets of T cells involved in the maintenance of peripheral self‐tolerance by actively suppressing the activation and ...expansion of autoreactive T cells. Signalling through the interleukin‐2 receptor (IL‐2R) contributes to T cell tolerance by controlling three important aspects of regulatory T cell (Treg) biology. CD25 is the α‐chain of the IL‐2R that, in concert with the β‐chain and γ‐chain, constitutes the complete IL‐2R. CD25 contributes only to IL‐2 binding affinity but not to the recruitment of signalling molecules. However, its importance in the development of a normal immune response is emphasized by the finding that a truncation mutant of CD25 results in an immunodeficiency in humans characterized by an increased susceptibility to viral, bacterial and fungal infections. In 1997, Sharfe et al. described an infant with severe bacterial, viral and fungal infections. Counts of autologous T lymphocytes were moderately low, T cells displayed a weak proliferative response to mitogens in vitro and the patient displayed no rejection of an allogeneic skin graft. However, unlike children with severe combined immunodeficiency (SCID), besides not having circulating T cells, the patient also developed peripheral lymphocytic proliferation and autoimmune primary biliary cirrhosis. We present the first female Argentine patient with mutation in CD25 associated with chronic and severe inflammatory lung disease (follicular bronchiolitis with lymphocyte hyperplasia), eczema and infections. She has no expression of CD25 on CD4+ T cells and an extremely low amount of Tregs. The molecular study confirmed homozygous missense mutation in the alpha subunit of the IL‐2 receptor (CD25αR) (c. 122 a > c; p. Y41S).
We previously showed that 40 % of clinically stable patients hospitalised for community-acquired pneumonia (CAP) are not switched to oral therapy in a timely fashion because of physicians’ barriers. ...We aimed to decrease this proportion by implementing a novel protocol. In a multi-centre controlled before-and-after study, we evaluated the effect of an implementation strategy tailored to previously identified barriers to an early switch. In three Dutch hospitals, a protocol dictating a timely switch strategy was implemented using educational sessions, pocket reminders and active involvement of nursing staff. Primary outcomes were the proportion of patients switched timely and the duration of intravenous antibiotic therapy. Length of hospital stay (LOS), patient outcome, education effects 6 months after implementation and implementation costs were secondary outcomes. Statistical analysis was performed using mixed-effects models. Prior to implementation, 146 patients were included and, after implementation, 213 patients were included. The case mix was comparable. The implementation did not change the proportion of patients switched on time (66 %). The median duration of intravenous antibiotic administration decreased from 4 days interquartile range (IQR) 2–5 to 3 days (IQR 2–4), a decrease of 21 % 95 % confidence interval (CI) 11 %; 30 %) in the multi-variable analysis. LOS and patient outcome were comparable before and after implementation. Forty-three percent (56/129) of physicians attended the educational sessions. After 6 months, 24 % (10/42) of the interviewed attendees remembered the protocol’s main message. Cumulative implementation costs were €5,798 (€20/reduced intravenous treatment day). An implementation strategy tailored to previously identified barriers reduced the duration of intravenous antibiotic administration in hospitalised CAP patients by 1 day, at minimal cost.
We describe nine patients (eight aged <1 year) clinically diagnosed with pertussis yet laboratory-confirmed with Bordetella holmesii infections, a human pathogen normally isolated from blood. Most ...patients reported cough and cold symptoms. No death was reported. We report B. holmesii isolation in infants with respiratory symptoms in Argentina.
The time to first antibiotic dose (TFAD) has been mentioned as an important performance indicator in community-acquired pneumonia (CAP). However, the advice to minimise TFAD to 4 hours (4 h) is only ...based on database studies. We prospectively studied the effect of minimising the TFAD on the early clinical outcome of moderate-severe CAP. On admission, patients' medical data and TFAD were recorded. Early clinical failure was expressed as the proportion of patients with clinical instability, admission to the intensive care unit (ICU) or mortality on day three. Of 166 patients included in the study, 27 patients (29.7%) with TFAD <4 h had early clinical failure compared to 23 patients (37.7%) with TFAD >4 h (odds ratio OR 0.69; 95% confidence interval CI 0.35-1.35). In multivariate analysis, the pneumonia severity index (OR 1.03; 95%CI 1.01-1.04), confusion (OR 2.63; 95%CI 1.14-6.06), Staphylococcus aureus infection (OR 7.26; 95%CI 1.33-39.69) and multilobar pneumonia (OR 2.40; 95%CI 1.11-5.22) but not TFAD were independently associated with early clinical failure. Clinical parameters on admission other than the TFAD predict early clinical outcome in moderate-severe CAP. In contrast to severe CAP necessitating treatment in the ICU directly, in the case of suspected moderate-severe CAP, there is time to establish a reliable diagnosis of CAP before antibiotics are administered. Therefore, the implementation of the TFAD as a performance indicator is not desirable.
Context:
Hypertensive disorders during pregnancy are associated with a wide range of maternal and fetal complications, and only a few risk factors are known for the development of these disorders ...during pregnancy. Conflicting and limited data are available on the relationship between thyroid (dys)function and the risk of hypertensive disorders of pregnancy.
Objective:
The objective of the investigation was to study the associations between early-pregnancy thyroid dysfunction, thyroid function within the normal range, and the risk of hypertensive disorders.
Design, Setting, and Participants:
In early pregnancy, serum TSH, free T4 (FT4), and thyroperoxidase antibody (TPOAb) levels were determined in 5153 pregnant women. No interventions were done. The associations of thyroid function with the risk of hypertensive disorders were studied.
Main Outcome Measures:
Mean blood pressures and hypertensive disorders, including pregnancy-induced hypertension (n = 209) and preeclampsia (n = 136), were measured.
Results:
Hyperthyroid mothers had a higher risk of hypertensive disorders odds ratio (OR) 3.40 95% confidence interval (CI) 1.46–7.91, P = .005, which was mainly due to an increased risk of pregnancy-induced hypertension OR 4.18 (95% CI 1.57–11.1), P = .004. Hypothyroidism and hypothyroxinemia were not associated with hypertensive disorders. Within the normal range, the high-normal FT4 levels were associated with an increased risk of hypertensive disorders OR 1.62 (95% CI 1.06–2.47), P = .03, which was mainly due to an increased risk of preeclampsia OR 2.06 (95% CI 1.04–4.08), P = .04. The TPOAb status was not associated with hypertensive disorders.
Conclusions:
We show that biochemical hyperthyroidism and also high-normal FT4 levels during early pregnancy are associated with an increased risk of hypertensive disorders. These data demonstrate that these associations are even seen for a mild variation in thyroid function within the normal range.
Maternal obesity may affect cardiovascular outcomes in the offspring. We examined the associations of maternal prepregnancy body mass index and gestational weight gain with childhood cardiac outcomes ...and explored whether these associations were explained by parental characteristics, infant characteristics or childhood body mass index.
In a population-based prospective cohort study among 4852 parents and their children, we obtained maternal weight before pregnancy and in early, mid- and late pregnancy. At age 6 years, we measured aortic root diameter (cm) and left ventricular dimensions. We calculated left ventricular mass (g), left ventricular mass index (g m(-2.7)), relative wall thickness ((2 × left ventricular posterior wall thickness)/left ventricular diameter), fractional shorting (%), eccentric left ventricular hypertrophy and concentric remodeling.
A one standard deviation score (SDS) higher maternal prepregnancy body mass index was associated with higher left ventricular mass (0.10 SDS (95% confidence interval (CI) 0.08, 0.13)), left ventricular mass index (0.06 SDS (95% CI 0.03, 0.09)) and aortic root diameter (0.09 SDS (95% CI 0.06, 0.12)), but not with relative wall thickness or fractional shortening. A one SDS higher maternal prepregnancy body mass index was associated with an increased risk of eccentric left ventricular hypertrophy (odds ratio 1.21 (95% CI 1.03, 1.41)), but not of concentric remodeling. When analyzing the effects of maternal weight in different periods simultaneously, only maternal prepregnancy weight and early pregnancy weight were associated with left ventricular mass, left ventricular mass index and aortic root diameter (P-values<0.05), independent of weight in other pregnancy periods. All observed associations were independent of parental and infant characteristics, but attenuated to non-significance after adjustment for childhood body mass index.
Maternal prepregnancy body mass index and weight gain in early pregnancy are both associated with offspring cardiac structure in childhood, but these associations seem to be fully explained by childhood body mass index.
Summary
Objective
Maternal prepregnancy obesity and excessive gestational weight gain are associated with pregnancy complications. Thyroid function is related to differences in body mass index (BMI) ...in adult populations. We examined the associations of maternal thyroid function in early pregnancy with maternal BMI and weight gain during pregnancy.
Design and methods
In a population‐based prospective cohort study among 5726 mothers, we measured maternal TSH and FT4 levels at 13.5 weeks of gestation (95% range: 9.7‐17.6 weeks). Maternal weight was assessed before pregnancy and in each trimester.
Results
Higher maternal TSH levels were associated with higher prepregnancy BMI (difference: 0.18 kg/m2 95% CI: 0.01, 0.36 per SD increase in maternal TSH level) and higher total gestational weight gain (difference: 0.02 kg/wk 95% CI: 0.01, 0.03 per SD increase in maternal TSH level). Higher maternal FT4 levels were associated with lower prepregnancy BMI (difference: −0.44 kg/m2 95% CI: −0.63, −0.26 per SD increase in maternal FT4 level) and lower total gestational weight gain (difference: −0.01 kg/wk 95% CI: −0.02, −0.01 per SD increase in maternal FT4 level). The associations of maternal thyroid function with weight gain in early pregnancy were stronger than those with weight gain in mid and late‐pregnancy. Maternal hypothyroidism was associated with higher prepregnancy BMI and early pregnancy weight gain, whereas opposite effects were observed for maternal hyperthyroidism (P<.05).
Conclusions
Higher maternal TSH level and lower FT4 level in early pregnancy are associated with higher prepregnancy BMI and higher gestational weight gain. Further studies are needed to explore maternal and foetal consequences.
To determine the best technique for measuring mesial-distal tooth widths on digital models.
The individual mesial-distal tooth widths were measured (first molar to first molar, maxillary and ...mandibular) on 32 stone casts and corresponding digital models (emodels, GeoDigm, Chanhassen, Minn). The digital models were measured using five different techniques: occlusal aspect, occlusal aspect zooming in on each individual tooth, facial aspect rotating as needed, facial aspect from three standard positions (R buccal, facial, and L buccal), and qualitatively rotating the model in any position deemed necessary. Measurements were repeated three times at least 1 week apart. The operator time needed to complete each set of measurements was recorded.
Four of five digital measurement techniques (except for the facial aspect from three standard positions) showed a slight positive bias (overestimation in measured width) compared with stone cast measurements. Measuring from the occlusal aspect resulted in the greatest Pearson correlation (98.509%), the least Altman-Bland standard deviation of differences value (1.881 mm), and the second fastest measuring time (2 minutes 3 seconds). Qualitatively rotating the model had similar Pearson correlation and Altman-Bland values to the Occlusal technique but took the longest time to measure (7 minutes 1 second).
The Occlusal measurement technique for digital models was the best combination of accuracy, repeatability, and speed of measurement.
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