Diagnostic Pitfalls of Macrocephaly and Intracranial Dural Arteriovenous Fistulas: Connecting the Dots With the Red Flags.

Macrocephaly is defined as an abnormal increase in head circumference greater than two standard deviations above the mean for a given age and sex. We present the case of a 16-month-old boy with congenital progressive macrocephaly, who was referred to our hospital for a ventriculoperitoneal shunt placement for external hydrocephalus diagnosed at 13 months of age. The patient had a febrile seizure 12 hours after the shunt was placed and the emergency CT exam revealed collapsed ventricles and a right frontal subdural collection, suggestive of an over-drainage and intracranial hypotension. A subsequent electroencephalogram (EEG) revealed some anomalies, but the patient was discharged two days later due to having no neurological symptoms after being placed on anticonvulsants. The patient returned to the hospital one week later due to recurrent seizures. Further clinical examination revealed prominent and tortuous veins of the skull, palpated in the left occipital region. A thrill and a left carotid murmur were heard during auscultation. A subsequent brain MRI with MR arteriography and venography was performed in search of an explanation for hydrocephaly. The sequences were suggestive of a dural arteriovenous fistula, which was confirmed and then treated using coils during an interventional angiography. A second procedure was performed two months later to complete the embolization, with subsequent imaging follow-ups showing the procedure to have been successful. The measurement of the cranial circumference, its regular evaluation, and its evolution allow a hierarchical diagnosis strategy by distinguishing primary and secondary macrocephaly, progressive or not. Dural arteriovenous fistulas (DAVF) are an under-appreciated cause of macrocephaly, with which they are associated in 35% of cases. Intracranial DAVFs are pathologic shunts between dural arteries and dural venous sinuses, meningeal veins, or cortical veins. Patients with DAVFs may be completely asymptomatic. Symptoms, when present, may range from neurological deficits, seizures, and hydrocephaly to fatal hemorrhage. The symptoms depend on the location and venous and drainage patterns of the DAVF. They can be difficult to identify on routine MRIs unless specifically searched for, especially in cases of technically suboptimal examinations. We aim to give a practical approach to identify the clinical clues that warrant further investigation. Several specific protocols exist regarding the management of macrocephaly and should be followed carefully once a diagnosis has been reached, but further studies are needed to integrate more clinical and neuroimaging findings to permit an early diagnosis.

Influence of Multiplex PCR in the Management of Antibiotic Treatment in Patients with Bacteremia.

The multiplex PCR assay can be a helpful diagnostic tool for patients with bacteremia. Herein, we assessed the impact of a Blood Culture Identification Panel (BCID) on both the diagnosis and treatment of patients with bacteremia. We performed a retrospective study using laboratory and clinical data to evaluate the impact of syndromic testing using a multiplex PCR testing system (BioFire® FilmArray) for the management of patients with bloodstream infections. BCID detected the pathogen in 102 (87.9%) samples out of the 116 positive blood cultures tested. The average time from the blood culture collection to the communication of the molecular test result was 23.93 h (range: 10.67-69.27 h). The main pathogen detected was Klebsiella pneumoniae (17.6%). The antimicrobial therapy was changed in accordance with the BCID results in 28 (40.6%) out of the 69 cases, wherein the treatment could have been theoretically adjusted. This allowed the adjustment of the therapy to be performed 1305.1 h faster than it would have been possible if conventional diagnostic methods had been used; this was the case for only 35.1% of the time gained if treatment was adjusted for all patients with positive BCID. Thus, although molecular tests can make a difference in the management of bloodstream infections, there is room for improvement in the clinical application of BCID results.

Changes in Use of Blood Cultures in a COVID-19-Dedicated Tertiary Hospital.

Blood cultures should be collected within an hour in the setting of sepsis/septic shock. The contamination rate should be below 3%. Worldwide reports have described an increase in blood contamination rates during the COVID-19 pandemic. We performed a retrospective analysis of the blood cultures collected during a 10-month period (March−December 2020) at NIID "Prof. Dr. Matei Balș". The results were compared with data from the pre-pandemic period (March−December 2016) and with the existing data in the literature. During the pandemic, there was a significant decrease in the number of blood cultures collected (1274 blood cultures in 2020 vs. 5399 in 2016). The contamination rate was higher in 2020 (11.7%) compared to 2016 (8.2%), p < 0.001. The rate of infectious episodes in which the etiological agent was identified was constant: 11% in 2020 versus 11.9% in 2016, p = 0.479, but there were fewer invasive bacterial/fungal infections: 0.95/1000 patient days in 2020 vs. 2.39/1000 patient days in 2016, p < 0.001. We observed a change in the species distribution. The Gram-negative isolate's proportion increased from 50.6% to 63.1% and the gram-positive isolate's proportion decreased from 31.8% to 19%. Collection of a low number of blood cultures and a high contamination rate was identified in our clinic. In order to improve the usefulness of blood cultures as a diagnostic method, at least two sets should be collected in aseptic conditions.

An efficient method for identifying statistical interactors in gene association networks.

Network reconstruction is a main goal of many biological endeavors. Graphical Gaussian models (GGMs) are often used since the underlying assumptions are well understood, the graph is readily estimated by calculating the partial correlation (paCor) matrix, and its interpretation is straightforward. In spite of these advantages, GGMs are limited in that interactions are not accommodated as the underlying multivariate normality assumption allows for linear dependencies only. As we show, when applied in the presence of interactions, the GGM framework can lead to incorrect inference regarding dependence. Identifying the exact dependence structure in this context is a difficult problem, largely because an analogue of the paCor matrix is not available and dependencies can involve many nodes. We here present a computationally efficient approach to identify bivariate interactions in networks. A key element is recognizing that interactions have a marginal linear effect and as a result information about their presence can be obtained from the paCor matrix. Theoretical derivations for the exact effect are presented and used to motivate the approach; and simulations suggest that the method works well, even in fairly complicated scenarios. Practical advantages are demonstrated in analyses of data from a breast cancer study.

ß-AR polymorphisms and glycemic and lipid parameters in hypertensive individuals receiving carvedilol or metoprolol.

BACKGROUND: ß-Blocker therapy and ß-adrenergic receptor (ß-AR) polymorphisms are associated with increases in glucose and lipid levels. We investigated associations of common ß1 and ß2-AR single-nucleotide polymorphisms (SNPs) with metabolic and lipid variables, and examined interactions with ß-blocker treatment assignment to affect these parameters. METHODS: This was a post hoc analysis of a double-blinded clinical trial of nondiabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3 months, and after 6 months. Genotypes for ß1-AR SNPs Ser49Gly & Gly389Arg and ß2-AR Arg16Gly & Gln27Glu were determined. Multivariable mixed models were used to examine associations between ß-AR polymorphisms, metabolic parameters, and SNP interactions with ß-blocker therapy (p(interaction)). RESULTS: The 322 subjects were mean (s.d.) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol and 9.9% on carvedilol (P = 0.015). In univariate models, the Gln27Gln genotype had higher overall insulin levels with ß-blockade compared to the Glu27Glu genotype (P = 0.006). Both Arg16Gly (P = 0.012) and Gln27Glu (P = 0.037) SNPs were associated with higher triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (p(int) = 0.048). CONCLUSIONS: These data suggest that insulin and triglycerides may be influenced by ß2-AR polymorphisms in patients taking ß blockers.