Cisternal nicardipine for prevention of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a comparative retrospective cohort study.

PURPOSE: Intrathecal vasoactive drugs have been proposed in patients with aneurysmal subarachnoid hemorrhage (aSAH) to manage cerebral vasospasm (CV). We analyzed the efficacy of intracisternal nicardipine compared to intraventricular administration to a control group (CG) to determine its impact on delayed cerebral ischemia (DCI) and functional outcomes. Secondary outcomes included the need for intra-arterial angioplasties and the safety profile. METHODS: We performed a retrospective analysis of prospectively collected data of all adult patients admitted for a high modified Fisher grade aSAH between January 2015 and April 2022. All patients with significant radiological CV were included. Three groups of patients were defined based on the CV management: cisternal nicardipine (CN), ventricular nicardipine (VN), and no intrathecal nicardipine (control group). RESULTS: Seventy patients met the inclusion criteria. Eleven patients received intracisternal nicardipine, 18 intraventricular nicardipine, and 41 belonged to the control group. No cases of DCI were observed in the CN group (p = 0.02). Patients with intracisternal nicardipine had a reduced number of intra-arterial angioplasties when compared to the control group (p = 0.03). The safety profile analysis showed no difference in complications across the three groups. Intrathecal (ventricular or cisternal) nicardipine therapy improved functional outcomes at 6 months (p = 0.04) when compared to the control group. CONCLUSION: Administration of intrathecal nicardipine for moderate to severe CV reduces the rate of DCI and improved long-term functional outcomes in patients with high modified Fisher grade aSAH. This study also showed a relative benefit of cisternal over intraventricular nicardipine, thereby reducing the number of angioplasties performed in the post-treatment phase. However, these preliminary results should be confirmed with future prospective studies.

Simplifying Access to Targeted Protein Degraders via Nickel Electrocatalytic Cross-Coupling.

C-C linked glutarimide-containing structures with direct utility in the preparation of cereblon-based degraders (PROTACs, CELMoDs) can be assessed in a single step from inexpensive, commercial α-bromoglutarimide through a unique Brønsted-acid assisted Ni-electrocatalytic approach. The reaction tolerates a broad array of functional groups that are historically problematic and can be applied to the simplified synthesis of dozens of known compounds that have only been procured through laborious, wasteful, multi-step sequences. The reaction is scalable in both batch and flow and features a trivial procedure wherein the most time-consuming aspect of reaction setup is weighing out the starting materials.

Metabolomic disorders: confirmed presence of potentially treatable abnormalities in patients with treatment refractory depression and suicidal behavior.

BACKGROUND: Refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. Approximately 15% of patients with major depressive disorder are refractory to currently available treatments. We hypothesized metabolic abnormalities contributing to treatment refractory depression are associated with distinct findings identifiable in the cerebrospinal fluid (CSF). Our hypothesis was confirmed by a previous small case-controlled study. Here we present a second, larger replication study. METHODS: We conducted a case-controlled, targeted, metabolomic evaluation of 141 adolescent and adult patients with well-characterized history of depression refractory to three maximum-dose, adequate-duration medication treatments, and 36 healthy controls. Plasma, urine, and CSF metabolic profiling were performed by coupled gas chromatography/mass spectrometry, and high-performance liquid chromatography, electrospray ionization, tandem mass spectrometry. RESULTS: Abnormalities were identified in 67 of 141 treatment refractory depression participants. The CSF abnormalities included: low cerebral folate (n = 20), low tetrahydrobiopterin intermediates (n = 11), and borderline low-tetrahydrobiopterin intermediates (n = 20). Serum abnormalities included abnormal acylcarnitine profile (n = 12) and abnormal serum amino acids (n = 20). Eighteen patients presented with two or more abnormal metabolic findings. Sixteen patients with cerebral folate deficiency and seven with low tetrahydrobiopterin intermediates in CSF showed improvement in depression symptom inventories after treatment with folinic acid and sapropterin, respectively. No healthy controls had a metabolite abnormality. CONCLUSIONS: Examination of metabolic disorders in treatment refractory depression identified an unexpectedly large proportion of patients with potentially treatable abnormalities. The etiology of these abnormalities and their potential roles in pathogenesis remain to be determined.

Documenting the development, adoption and pre-ebola implementation of Liberia's integrated disease surveillance and response (IDSR) strategy.

BACKGROUND: In the immediate aftermath of a 14-year civil conflict that disrupted the health system, Liberia adopted the internationally recommended integrated disease surveillance and response (IDSR) strategy in 2004. Despite this, Liberia was among the three West African countries ravaged by the worst Ebola epidemic in history from 2014 to 2016. This paper describes successes, failures, strengths, and weaknesses in the development, adoption, and implementation of IDSR following the civil war and up until the outbreak of Ebola, from 2004 to early 2014. METHODS: We reviewed 112 official Government documents and peer-reviewed articles and conducted 29 in-depth interviews with key informants from December 2021 to March 2022 to gain perspectives on IDSR in the post-conflict and pre-Ebola era in Liberia. We assessed the core and supportive functions of IDSR, such as notification of priority diseases, confirmation, reporting, analysis, investigation, response, feedback, monitoring, staff training, supervision, communication, and financial resources. Data were triangulated and presented via emerging themes and in-depth accounts to describe the context of IDSR introduction and implementation, and the barriers surrounding it. RESULTS: Despite the adoption of the IDSR framework, Liberia failed to secure the resources-human, logistical, and financial-to support effective implementation over the 10-year period. Documents and interview reports demonstrate numerous challenges prior to Ebola: the surveillance system lacked key components of IDSR including laboratory testing capacity, disease reporting, risk communication, community engagement, and staff supervision systems. Insufficient financial support and an abundance of vertical programs further impeded progress. In-depth accounts by donors and key governmental informants demonstrate that although the system had a role in detecting Ebola in Liberia, it could not respond effectively to control the disease. CONCLUSION: Our findings suggest that post-war, Liberia's health system intended to prioritize epidemic preparedness and response with the adoption of IDSR. However, insufficient investment and systems development meant IDSR was not well implemented, leaving the country vulnerable to the devastating impact of the Ebola epidemic.

Occipital interhemispheric transtentorial approach in pediatric patients for lesions of the superomedial cerebellum: operative findings and results.

BACKGROUND: The occipital interhemispheric transtentorial (OITT) approach is frequently used for accessing the pineal region. There are scarce reports of using the OITT to access superior cerebellar lesions. This approach affords the patient several advantages over traditional posterior fossa approaches. PURPOSE: This study is to describe and evaluate clinical outcomes in a single surgeon case series of the OITT approach for pediatric patients with lesions of the superior cerebellum. METHODS: All pediatric patients who underwent an OITT craniotomy for a superior cerebellar lesion by a single surgeon over a 5-year period were included in this retrospective analysis. Patient demographics and clinical data were collected. RESULTS: Thirteen pediatric patients were identified. Cases included twelve tumors and one arteriovenous malformation. Gross total resection was achieved in 92% of cases. No patients developed posterior fossa syndrome. Two patients had transient homonymous hemianopsia that resolved by 1 month post-operatively. There were no permanent neurological deficits. CONCLUSION: For superomedial cerebellar lesions presenting to the tentorial surface of the superior cerebellum in patients with normal to steep tentorial angles, the OITT approach is effective and safe. This approach has a low risk of posterior fossa syndrome and permanent visual deficits when applied appropriately. Patient selection is critical for maximizing the advantages of the OITT for superior cerebellar lesions.

Endovascular treatment of pediatric basilar artery aneurysms: case series and literature review.

PURPOSE: Pediatric basilar artery aneurysms are rare and challenging to treat. Microsurgical options and standard endovascular coiling are often undesirable choices for treatment of this pathology. Additional endovascular strategies are needed. METHODS: Presentation, diagnosis, and management of pediatric basilar aneurysms were reviewed, with an emphasis on endovascular treatment strategies. Our case series of 2 patients was presented in detail, one treated with flow diversion and vessel sacrifice and one treated with stent-assisted coiling. An extensive review of the literation was performed to find other examples of pediatric basilar artery aneurysms treated with endovascular techniques. RESULTS: Twenty-nine studies met inclusion criteria. Fifty-nine aneurysms in 58 patients were treated using endovascular techniques. Mortality rate was 10.3% (6/58) and a poor outcome (GOS 1-3) occurred in 15.5% (9/58). There were 4 reported recurrences requiring retreatment; however, only 46.5% of patients had reported follow-up of at least 1 year. 71.1% (42/59) were dissecting aneurysms. CONCLUSION: Basilar artery aneurysms in the pediatric population are rare, commonly giant and fusiform, and often not amenable to microsurgical or coiling techniques. The surrounding vasculature, location, size, and morphology of the aneurysm along with the durability of treatment must be considered in treatment decisions. With proper patient selection, stent-assisted coiling and flow diversion may increase the durability and safety of endovascular treatment in this population.

Resection of the contrast-enhancing tumor in diffuse gliomas bordering eloquent areas using electrophysiology and 5-ALA fluorescence: evaluation of resection rates and neurological outcome-a systematic review and meta-analysis.

Independently, both 5-aminolevulinic acid (5-ALA) and intraoperative neuromonitoring (IONM) have been shown to improve outcomes with high-grade gliomas (HGG). The interplay and overlap of both techniques are scarcely reported in the literature. We performed a systematic review and meta-analysis focusing on the concomitant use of 5-ALA and intraoperative mapping for HGG located within eloquent cortex. Using PRISMA guidelines, we reviewed articles published between May 2006 and December 2022 for patients with HGG in eloquent cortex who underwent microsurgical resection using intraoperative mapping and 5-ALA fluorescence guidance. Extent of resection was the primary outcome. The secondary outcome was new neurological deficit at day 1 after surgery and persistent at day 90 after surgery. Overall rate of complete resection of the enhancing tumor (CRET) was 73.3% (range: 61.9-84.8%, p < .001). Complete 5-ALA resection was performed in 62.4% (range: 28.1-96.7%, p < .001). Surgery was stopped due to mapping findings in 20.5% (range: 15.6-25.4%, p < .001). Neurological decline at day 1 after surgery was 29.2% (range: 9.8-48.5%, p = 0.003). Persistent neurological decline at day 90 after surgery was 4.6% (range: 0.4-8.7%, p = 0.03). Maximal safe resection guided by IONM and 5-ALA for high-grade gliomas in eloquent areas is achievable in a high percentage of cases (73.3% CRET and 62.4% complete 5-ALA resection). Persistent neurological decline at postoperative day 90 is as low as 4.6%. A balance between 5-ALA and IONM should be maintained for a better quality of life while maximizing oncological control.

Single fraction and hypofractionated radiosurgery for perioptic meningiomas-tumor control and visual outcomes: a systematic review and meta-analysis.

Perioptic meningiomas, defined as those that are less than 3 mm from the optic apparatus, are challenging to treat with stereotactic radiosurgery (SRS). Tumor control must be weighed against the risk of radiation-induced optic neuropathy (RION), as both tumor progression and RION can lead to visual decline. We performed a systematic review and meta-analysis of single fraction SRS and hypofractionated radiosurgery (hfRS) for perioptic meningiomas, evaluating tumor control and visual preservation rates. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed articles published between 1968 and December 8, 2022. We retained 5 studies reporting 865 patients, 438 cases treated in single fraction, while 427 with hfRS. For single fraction SRS, the overall rate of tumor control was 95.1%, with actuarial rates at 5 and 10 years of 96% and 89%, respectively; tumor progression was 7.7%. The rate of visual stability was 90.4%, including visual improvement in 29.3%. The rate of visual decline was 9.6%, including blindness in 1.2%. For hfRS, the overall rate of tumor control was 95.6% (range 92.1-99.1, p < 0.001); tumor progression was 4.4% (range 0.9-7.9, p = 0.01). Overall rate of visual stability was 94.9% (range 90.9-98.9, p < 0.001), including visual improvement in 22.7% (range 5.0-40.3, p = 0.01); visual decline was 5.1% (range 1.1-9.1, p = 0.013). SRS is an effective and safe treatment option for perioptic meningiomas. Both hypofractionated regimens and single fraction SRS can be considered.

Proton beam radiation therapy for vestibular schwannomas-tumor control and hearing preservation rates: a systematic review and meta-analysis.

OBJECTIVE: Proton beam therapy is considered, by some authors, as having the advantage of delivering dose distributions more conformal to target compared with stereotactic radiosurgery (SRS). Here, we performed a systematic review and meta-analysis of proton beam for VSs, evaluating tumor control and cranial nerve preservation rates, particularly with regard to facial and hearing preservation. METHODS: We reviewed, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) articles published between 1968 and September 30, 2022. We retained 8 studies reporting 587 patients. RESULTS: Overall rate of tumor control (both stability and decrease in volume) was 95.4% (range 93.5-97.2%, p heterogeneity= 0.77, p<0.001). Overall rate of tumor progression was 4.6% (range 2.8-6.5%, p heterogeneity < 0.77, p<0.001). Overall rate of trigeminal nerve preservation (absence of numbness) was 95.6% (range 93.5-97.7%, I2 = 11.44%, p heterogeneity= 0.34, p<0.001). Overall rate of facial nerve preservation was 93.7% (range 89.6-97.7%, I2 = 76.27%, p heterogeneity<0.001, p<0.001). Overall rate of hearing preservation was 40.6% (range 29.4-51.8%, I2 = 43.36%, p heterogeneity= 0.1, p<0.001). CONCLUSION: Proton beam therapy for VSs achieves high tumor control rates, as high as 95.4%. Facial rate preservation overall rates are 93%, which is lower compared to the most SRS series. Compared with most currently reported SRS techniques, proton beam radiation therapy for VSs does not offer an advantage for facial and hearing preservation compared to most of the currently reported SRS series.

Implementation of the Enhanced Recovery After Surgery (ERAS®) program in neurosurgery.

BACKGROUND: Over the past decade, Enhanced Recovery After Surgery (ERAS®) guidelines have been proven to simplify postoperative care and improve recovery in several surgical disciplines. The authors set out to create and launch an ERAS® program for cranial neurosurgery that meets official ERAS® Society standards. The authors summarize the successive steps taken to achieve this goal in two specific neurosurgical conditions and describe the challenges they faced. METHODS: Pituitary neuroendocrine tumors (Pit-NET) resected by a transsphenoidal approach and craniosynostosis (Cs) repair were selected as appropriate targets for the implementation of ERAS® program in the Department of Neurosurgery. A multidisciplinary team with experience in managing these pathologies was created. A specialized ERAS® nurse coordinator was hired. An ERAS® certification process was performed involving 4 seminars separated by 3 active phases under the supervision of an ERAS® coach. RESULTS: The ERAS® Pit-NET team included 8 active members. The ERAS® Cs team included 12 active members. Through the ERAS® certification process, areas for improvement were identified, local protocols were written, and the ERAS® program was implemented. Patient-centered strategies were developed to increase compliance with the ERAS® protocols. A prospective database was designed for ongoing program evaluation. Certification was achieved in 18 months. Direct costs and time requirements are reported. CONCLUSION: Successful ERAS® certification requires a committed multidisciplinary team, an ERAS® coach, and a dedicated nurse coordinator.

Ideality in Context: Motivations for Total Synthesis.

Total synthesis-the ultimate proving ground for the invention and field-testing of new methods, exploration of disruptive strategies, final structure confirmation, and empowerment of medicinal chemistry on natural products-is one of the oldest and most enduring subfields of organic chemistry. In the early days of this field, its sole emphasis focused on debunking the concept of vitalism, that living organisms could create forms of matter accessible only to them. Emphasis then turned to the use of synthesis to degrade and reconstitute natural products to establish structure and answer questions about biosynthesis. It then evolved to not only an intricate science but also a celebrated form of art. As the field progressed, a more orderly and logical approach emerged that served to standardize the process. These developments even opened up the possibility of computer-aided design using retrosynthetic analysis. Finally, the elevation of this field to even higher levels of sophistication showed that it was feasible to synthesize any natural product, regardless of complexity, in a laboratory. During this remarkable evolution, as has been reviewed elsewhere, many of the principles and methods of organic synthesis were refined and galvanized. In the modern era, students and practitioners are still magnetically attracted to this field due to the excitement of the journey, the exhilaration of creation, and the opportunity to invent solutions to challenges that still persist. Contemporary total synthesis is less concerned with demonstrating a proof of concept or a feasible approach but rather aims for increased efficiency, scalability, and even "ideality." In general, the molecules of Nature are created biosynthetically with levels of practicality that are still unimaginable using the tools of modern synthesis. Thus, as the community strives to do more with less (i.e., innovation), total synthesis is now focused on a pursuit for simplicity rather than a competition for maximal complexity. In doing so, the practitioner must devise outside-the-box strategies supplemented with forgotten or newly invented methods to reduce step count and increase the overall economy of the approach. The downstream applications of this pursuit not only empower students who often go on to apply these skills in the private sector but also lead to new discoveries that can impact numerous disciplines of societal importance. This account traces some select case studies from our laboratory over the past five years that vividly demonstrate our own motivation for dedicating so much effort to this classic field. In aiming for simplicity, we focus on the elusive goal of achieving ideality, a term that, when taken in the proper context, can serve as a guiding light to point the way to furthering progress in organic synthesis.

The effectiveness of supervision strategies to improve health care provider practices in low- and middle-income countries: secondary analysis of a systematic review.

BACKGROUND: Although supervision is a ubiquitous approach to support health programs and improve health care provider (HCP) performance in low- and middle-income countries (LMICs), quantitative evidence of its effects is unclear. The objectives of this study are to describe the effect of supervision strategies on HCP practices in LMICs and to identify attributes associated with greater effectiveness of routine supervision. METHODS: We performed a secondary analysis of data on HCP practice outcomes (e.g., percentage of patients correctly treated) from a systematic review on improving HCP performance. The review included controlled trials and interrupted time series studies. We described distributions of effect sizes (defined as percentage-point [%-point] changes) for each supervision strategy. To identify attributes associated with supervision effectiveness, we performed random-effects linear regression modeling and examined studies that directly compared different approaches of routine supervision. RESULTS: We analyzed data from 81 studies from 36 countries. For professional HCPs, such as nurses and physicians, primarily working at health facilities, routine supervision (median improvement when compared to controls: 10.7%-points; IQR: 9.9, 27.9) had similar effects on HCP practices as audit with feedback (median improvement: 10.1%-points; IQR: 6.2, 23.7). Two attributes were associated with greater mean effectiveness of routine supervision (p < 0.10): supervisors received supervision (by 8.8-11.5%-points), and supervisors participated in problem-solving with HCPs (by 14.2-20.8%-points). Training for supervisors and use of a checklist during supervision visits were not associated with effectiveness. The effects of supervision frequency (i.e., number of visits per year) and dose (i.e., the number of supervision visits during a study) were unclear. For lay HCPs, the effect of routine supervision was difficult to characterize because few studies existed, and effectiveness in those studies varied considerably. Evidence quality for all findings was low primarily because many studies had a high risk of bias. CONCLUSIONS: Although evidence is limited, to promote more effective supervision, our study supports supervising supervisors and having supervisors engage in problem-solving with HCPs. Supervision's integral role in health systems in LMICs justifies a more deliberate research agenda to identify how to deliver supervision to optimize its effect on HCP practices.

Tentorial peeling during combined petrosal approach: a cadaveric dissection.

BACKGROUND: The combined petrosal approach is an excellent method to access the petroclival region but has the inherent risk of injury to the temporal lobe and Vein of Labbé. Tentorial peeling has the potential to largely eliminate these risks during the classic combined transpetrosal approach. METHODS: Anatomical dissection of three adult injected non-formalin fixed cadaveric heads was performed. Combined petrosal approach with tentorial peeling was completed. A tentorial incision just superior and parallel to the superior petrosal sinus was made to enable peeling of the tentorium into two layers, the posterior fossa tentorial leaf (PFTL), and the temporal tentorial leaf (TTL). RESULTS: Tentorial peeling clearly exposed the continuity between the temporal dura and the TTL as well as the continuity between the presigmoid dura and the PFTL. This enabled the creation of a large dural flap extending to the tentorial incisura, providing wide access to the petroclival region without any exposure of the temporal lobe and/or basal temporal veins. Techniques to create the dural flap without trochlear nerve injury were also explored. CONCLUSION: The technique of tentorial peeling into two distinct layers has the potential to reduce the morbidity associated with temporal lobe retraction and venous injury. Further cadaveric studies and surgical case series are needed to validate this important surgical nuance in transpetrosal approaches.

Strategies to promote evidence use for health programme improvement: learning from the experiences of embedded implementation research teams in Latin America and the Caribbean.

BACKGROUND: To achieve global health targets, innovative approaches are needed to strengthen the implementation of efficacious interventions. New approaches in implementation research that bring together health system decision-makers alongside researchers to collaboratively design, produce and apply research evidence are gaining traction. Embedded implementation research (EIR) approaches led by decision-maker principal investigators (DM PIs) appear promising in this regard. Our aim is to describe the strategies study teams employ in the post-research phase of EIR to promote evidence-informed programme or policy improvement. METHODS: We conducted a prospective, comparative case study of an EIR initiative in Bolivia, Colombia and Dominican Republic. Guided by a conceptual framework on EIR, we used semi-structured key informant interviews (n = 51) and document reviews (n = 20) to examine three decision-maker-led study teams ("cases"). Focusing on three processes (communication/dissemination, stakeholder engagement with evidence, integrating evidence in decision-making) and the main outcome (enacting improvements), we used thematic analysis to identify associated strategies and enabling or hindering factors. RESULTS: Across cases, we observed diverse strategies, shaped substantially by whether the DM PI was positioned to lead the response to study findings within their sphere of work. We found two primary change pathways: (1) DM PIs implement remedial measures directly, and (2) DM PIs seek to influence other stakeholders to respond to study findings. Throughout the post-research phase, EIR teams adapted research use strategies based on the evolving context. CONCLUSIONS: EIR led by well-positioned DM PIs can facilitate impactful research translation efforts. We draw lessons around the importance of (1) understanding DM PI positionality, (2) ongoing assessment of the evolving context and stakeholders and (3) iterative adaptation to dynamic, uncertain circumstances. Findings may guide EIR practitioners in planning and conducting fit-for-purpose and context-sensitive strategies to advance the use of evidence for programme improvement.

Total Synthesis of Kibdelomycin.

A modular total synthesis of kibdelomycin is disclosed that should enable structure-activity relationship (SAR) studies of this interesting class of antibiotics. The route uses simple building blocks and addresses lingering questions about its structural assignment and relationship to amycolamicin, a recently described natural product reported to have a similar structure. Initial antibacterial assays reveal that both C-22 epimers (the N-glycosidic linkage) of the natural product have similar activity while structurally truncated analogs lose activity.

High-resolution epigenomic liquid biopsy for noninvasive phenotyping in pregnancy.

OBJECTIVE: We explored the potential of genome-wide epigenomic liquid biopsy for the comprehensive analysis of cell-free DNA (cfDNA) methylation signatures in maternal plasma in early gestation. METHOD: We used solution phase hybridization for targeted region capture of bisulfite-converted DNA obtained from plasma of pregnant women in early gestation and nonpregnant female controls. RESULTS: Targeted sequencing of ~80.5 Mb of the plasma methylome generated an average read depth across all 17 plasma samples of ~42x. We used these data to explore the pregnancy-specific characteristics of cfDNA methylation in plasma and found that pregnancy resulted in clearly detectable global alterations in DNA methylation patterns that were influenced by genomic location. We analyzed similar, previously published, data from first-trimester maternal leukocyte populations and gestational age-matched chorionic villus (CV) and confirmed that tissue-specific DNA methylation signatures in these samples had a significant influence on global and gene-specific methylation in the plasma of pregnant women. CONCLUSION: We describe an approach for targeted epigenomic liquid biopsy in pregnancy and discuss our findings in the context of noninvasive prenatal testing with respect to phenotypic pregnancy monitoring and the early detection of complex gestational phenotypes such as preeclampsia and preterm birth.

Placental transverse relaxation time (T2) estimated by MRI: Normal values and the correlation with birthweight.

INTRODUCTION: Placental transverse relaxation time (T2) assessed by MRI may have the potential to improve the antenatal identification of small for gestational age. The aims of this study were to provide normal values of placental T2 in relation to gestational age at the time of MRI and to explore the correlation between placental T2 and birthweight. MATERIAL AND METHODS: A mixed cohort of 112 singleton pregnancies was retrieved from our placental MRI research database. MRI was performed at 23.6-41.3 weeks of gestation in a 1.5T system (TE (8): 50-440 ms, TR: 4000 ms). Normal pregnancies were defined by uncomplicated pregnancies with normal obstetric outcome and birthweight deviation within ±1 SD of the expected for gestational age. The correlation between placental T2 and birthweight was investigated using the following outcomes; small for gestational age (birthweight ≤-2 SD of the expected for gestational age) and birthweight deviation (birthweight Z-scores). RESULTS: In normal pregnancies (n = 27), placenta T2 showed a significant negative linear correlation with gestational age (r = -.91, P = .0001) being 184 ms ± 15.94 ms (mean ± SD) at 20 weeks of gestation and 89 ms ± 15.94 ms at 40 weeks of gestation. Placental T2 was significantly reduced among small-for-gestational-age pregnancies (mean Z-score -1.95, P < .001). Moreover, we found a significant positive correlation between placenta T2 deviation (Z-score) and birthweight deviation (Z-score) (R2  = .26, P = .0001). CONCLUSIONS: This study provides normal values of placental T2 to be used in future studies on placental MRI. Placental T2 is closely related to birthweight and may improve the antenatal identification of small-for-gestational-age pregnancies.

[Hospital inhouse contact tracing-significant impact to patient care during the coronavirus pandemic]. / Krankenhausinterne Kontaktpersonennachverfolgung ­ Ein wichtiger Beitrag zur Sicherstellung der Patientenversorgung in der SARS-CoV-2-Pandemie.

BACKGROUND: As part of the SARS-CoV­2 pandemic, the district of Heinsberg developed into an infectiological epicentre for Germany in February 2020. Our hospital, which is located in the immediate vicinity, reacted very quickly in addition to adapting patient care by implementing an organizational structure for recording SARS-CoV-2-positive employees, patients and their contact persons. OBJECTIVES: The infections recorded in contact tracing were analysed and, based on an exemplary outbreak, infection chains and follow-up processes were evaluated. MATERIAL AND METHODS: Comprehensive data on contact types, oropharyngeal swab results for SARS-CoV­2 and quarantine days were documented and retrospectively evaluated using a self-developed database. RESULTS: Of the 568 employees recorded by in-house contact tracing, 32 employees (1.2%, n = 2567) were detected as SARS-CoV­2 positive. Of those, 50% (n = 16) tested positive due to contact tracing, 15.6% (n = 5) were recorded by routine smears and 34.4% (n = 11) were returning travellers. The variable PCR results of the control smears from these positive employees were noticeable. In 18.8% (n = 6) of the initially negative control smears, positive PCR results were found in the following control smear. The inhouse contact tracing team was able to detect infection clusters on non-COVID-19 wards at an early stage and, together with clinical hygiene and the public health department, initiated comprehensive measures to limit the spread of the virus. Infection chains could thus be interrupted. CONCLUSION: The work of the clinic's own contact tracing unit has proven to be an essential part of clinical pandemic management not least against the background of new waves of infection and is indispensable for the detection of local infection clusters.

Comparison of Ceftriaxone and Antipseudomonal ß-Lactam Antibiotics Utilized for Potential AmpC ß-Lactamase-Producing Organisms.

Background: Induction of antibiotic resistance is associated with increased morbidity and mortality in AmpC ß-lactamase producing Enterobacteriaceae. The use of ceftriaxone is controversial for treatment of these organisms due to concerns for inducible resistance. This study was designed to compare treatment failure rates between ceftriaxone and antipseudomonal ß-lactam antibiotics when used as definitive therapy for organisms most commonly associated with chromosomal AmpC ß-lactamase production. Methods: A retrospective, single-center cohort study was performed enrolling patients hospitalized with monomicrobial Enterobacter, Citrobacter, or Serratia spp. infections. The primary objective compared proportion of treatment failure between groups. All patients received either ceftriaxone or an antipseudomonal ß-lactam alone within 24 hours of culture finalization, and with a duration of at least 72 hours for definitive treatment. Treatment failure was defined as either clinical failure (abnormal white blood cell count or temperature on day 7 or 14 post-antibiotics) or microbiologic failure (regrowth of the same organism at same site within 14 or 21 days). Results: Of 192 total patients, treatment failure was observed in 24/71 patients (34%) receiving ceftriaxone and in 42/121 patients (35%) receiving antipseudomonal ß-lactam (P = .98). No difference was observed between clinical or microbiologic failure rates between groups. The ceftriaxone group had significantly more patients undergoing treatment for urinary tract infections (51% vs 17%, P < .001), but treatment failure rates remained similar between groups when comparing infections of all other sources. Conclusion: Ceftriaxone has comparable treatment failure rates to antipseudomonal ß-lactams for susceptible Enterobacteriaceae infections and may be considered as a therapeutic option. Further, prospective research is needed to validate optimal dosing and application in all sites of infection.

Non-invasive epigenomic molecular phenotyping of the human brain via liquid biopsy of cerebrospinal fluid and next generation sequencing.

Our goal was to undertake a genome-wide epigenomic liquid biopsy of cerebrospinal fluid (CSF) for the comprehensive analysis of cell-free DNA (cfDNA) methylation signatures in the human central nervous system (CNS). Solution-phase hybridization and massively parallel sequencing of bisulfite converted human DNA was employed to compare methylation signatures of cfDNA obtained from CSF with plasma. Recovery of cfDNA from CSF was relatively low (68-840 pg/mL) compared to plasma (2720-8390 pg/mL) and cfDNA fragments from CSF were approximately 20 bp shorter than their plasma-derived counterparts. Distributions of CpG methylation signatures were significantly altered between CSF and plasma, both globally and at the level of functional elements including exons, introns, CpG islands, and shores. Sliding window analysis was used to identify differentially methylated regions. We found numerous gene/locus-specific differences in CpG methylation between cfDNA from CSF and plasma. These loci were more frequently hypomethylated in CSF compared to plasma. Differentially methylated CpGs in CSF were identified in genes related to branching of neurites and neuronal development. Using the GTEx RNA expression database, we found clear association between tissue-specific gene expression in the CNS and cfDNA methylation patterns in CSF. Ingenuity pathway analysis of differentially methylated regions identified an enrichment of functional pathways related to neurobiology. In conclusion, we present a genome-wide analysis of DNA methylation in human CSF. Our methods and the resulting data demonstrate the potential of epigenomic liquid biopsy of the human CNS for molecular phenotyping of brain-derived DNA methylation signatures.