Routine Lumbar Puncture Research Articles

Full sample analysis of cerebral venous sinus thrombosis in ophthalmology inpatients

We hope that by analyzing the clinical features of cerebral venous sinus thrombosis (CVST), we can help ophthalmologists reduce misdiagnosis or delayed diagnosis. We evaluated 47 patients with CVST in terms of clinical manifestations. All cases were analyzed in terms of risk factors, clinical symptoms, ophthalmic examination, imaging examination and lumbar puncture. The body mass indices (BMIs) of 41 patients (87.2%; 95% CI, 77.7-96.8%) were≥24, which is overweight by Chinese standards. There were 22 patients (46.8%; 95% CI, 32.5-61.1%) with BMIs≥28, who were considered obese. Thirteen were hypertensive (27.7%; 95% CI, 14.9-40.5%). The initial symptoms included blurred vision (23, 48.9%; 95% CI, 34.6-63.2%), amaurosis fugax (13, 27.7%; 95% CI, 14.9-40.5%), headache (11 patients, 23.4%; 95% CI, 11.3-35.5%), dizziness (3, 6.4%; 95% CI, -0.6-13.4%), and bilateral diplopia (3, 6.4%; 95% CI, -0.6-13.4%). There were 9 patients (9, 19.2%; 95% CI, 7.9-30.4%) with blindness, 23 patients (48.9%; 95% CI, 34.6-63.2%) with pupillary abnormalities, and 40 patients (85.1%; 95% CI, 74.9-95.2%) with papilledema. Forty-three of the 45 patients who successfully underwent a routine lumbar puncture showed high intracranial pressure (91.7%; 95.6% CI, 89.6-101.6%). Finally, two cases are reported in greater detail for illustrative purposes. The main reasons interfering with the diagnosis of CVST might be its nonspecific ocular symptoms and the physicians' clinical thought process being limited to the scope of common ophthalmological diseases.

Determination of the Trans-Lamina Cribrosa Pressure Difference in a Community-Based Population and its Association with Open-Angle Glaucoma

To determine the trans-lamina cribrosa pressure difference (TLCPD) in a cohort of normal community-based patients and the relationship to primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). Retrospective cohort study of the Mayo Clinic Study of Aging. The Mayo Clinic Study of Aging is a prospective study evaluating the normal aging population. Mayo Clinic Study of Aging patients who underwent routine lumbar puncture (LP) studies with eye examinations were reviewed. The trans-lamina cribrosa pressure difference was calculated in 2 contexts of intraocular pressure (IOP): (1) maximum IOP at eye visit closest in time to the LP (closest-in-time TLCPD); and (2) IOP before IOP-lowering treatment (pretreatment IOP and pretreatment TLCPD) in POAG and NTG patients. Glaucoma patients without POAG or NTG were excluded. Regression analyses were performed to determine the relationship with glaucoma. IOP, intracranial pressure, TLCPD, POAG, normal-tension glaucoma (NTG) diagnosis, glaucoma parameters. Five hundred forty-eight patients were analyzed. Of these, there were 38 treated glaucoma patients (14 POAG and 24 NTG) and 510 nonglaucomatous patients. Cerebral spinal fluid (CSF) opening pressure was 155.0 ± 42.2 mmH2O in nonglaucomatous patients, 144.0 ± 34.0 mmH2O in POAG (P= 0.15 vs. nonglaucomatous patients), and 136.6 ± 29.3 mmH2O in NTG (P= 0.017 vs. nonglaucomatous patients). Intraocular pressure was 15.47 ± 2.9 mmHg in nonglaucomatous patients, 26.6 ± 3.7 mmHg in POAG, and 17.4 ± 3.4 mmHg in NTG. The closest-in-time TLCPD in the nonglaucomatous cohort was 4.07 ± 4.22 mmHg, which was lower than both the POAG cohort (7.19 ± 3.6 mmHg) and the NTG cohort (5.79 ± 4.5 mmHg, P= 0.04). Pretreatment TLCPD for the overall glaucoma cohort was 10.57 ± 6.1 mmHg. The POAG cohort had a higher pretreatment TLCPD (16.05 ± 5.2 mmHg) than the NTG cohort (7.37 ± 4.1 mmHg; P < 0.0001). Closest-in-time TLCPD for the nonglaucoma cohort (4.07± 4.2 mmHg) was significantly lower than pretreatment TLCPDs for both POAG (16.05 ± 5.2 mmHg; P < 0.0001) and NTG (7.37 ± 4.1 mmHg; P < 0.0001) cohorts. This study establishes the baseline TLCPD in a large cohort of normal, community-based patients. The differences in regression analysis between TLCPD and IOP suggests NTG pathophysiology is partially driven by TLCPD, but is also likely multifactorial. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Modified nusinersen intrathecal injection method: inclusion of a septal needle-free closed infusion connector.

Nusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly. This paper aims to describe the applicability and safety of this modified method. The modified intrathecal injection method (MIIM) mainly includes a septal needle-free closed infusion connector between the lumbar puncture needle and the syringe, besides the procedures of routine lumbar puncture. Its applicability and safety were evaluated through clinical observation. A total of 92 children with SMA have successfully received nusinersen treatment at our hospital using the modified method since 2019 without obvious adverse events related to the modified injection method. Based on the clinical feedback of operators, the advantages of the modified method include successfully injecting the total dose of nusinersen with constant injection rate and a more stable fixation of the puncture needle, as well as making the operator more relaxed. However, compared with the routine method, the procedure of the modified method has additional steps. The modified intrathecal injection method is an effective and safe method to inject nusinersen when weighing the pros and cons, and it may also be used for administering intrathecal injections of other expensive medicines or for patients with other strict requirements for intrathecal injection.

Emergency Medicine Images: Headache After a Lumbar Puncture

A 34-year-old man presented to the emergency department for a persistent, positional headache 3 weeks after a routine lumbar puncture (LP) for the workup of multiple sclerosis. The headache started gradually approximately 1 week after the uneventful LP and consistently improved with lying flat and worsened when upright. At a previous ED visit for this headache, an epidural blood patch was considered for postdural puncture headache (PDPH); however, the anesthesia service did not think a blood patch would be better than conservative treatment, given the usual benign course and the expectation for near-term resolution of symptoms with PDPH. With the patient experiencing persistent symptoms affecting his daily activities despite home analgesics, the ED clinician ordered a noncontrast head computed tomography scan (CT) (Figures 1 and 2). Figure 2Coronal noncontrast head computed tomographyt. There are bilateral convexity subdural hematomas (arrows) and subdural hematoma along the interhemispheric fissure (chevrons). The lateral ventricles partially effaced. View Large Image Figure Viewer Download Hi-res image Brian J. Ahern is a Physician Assistant at the Department of Emergency Medicine, William Beaumont Army Medical Center, Fort Bliss, TX. ORCID identifier: http://orcid.org/0000-0002-5701-3561. Lisa M. Jin is a Physician Assistant at the Department of Emergency Medicine, William Beaumont Army Medical Center, Fort Bliss, TX. Sean M. Sylvia is a Physician Assistant at the Department of Emergency Medicine, William Beaumont Army Medical Center, Fort Bliss, TX.

Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis.

Background: Tuberculosis meningitis (TBM) is the most lethal form of TB. It is difficult to treat in part due to poor or uncertain drug penetration into the central nervous system (CNS). To help fill this knowledge gap, we evaluated the cerebrospinal fluid (CSF) concentrations of fluoroquinolones and carbapenems in patients being treated for TBM. Methods: Serial serum and CSF samples were collected from hospitalized patients being treated for TBM. CSF was collected from routine lumbar punctures between alternating timepoints of 2 and 6h after drug administration to capture early and late CSF penetration. Rich serum sampling was collected after drug administration on day 28 for non-compartmental analysis. Results: Among 22 patients treated for TBM (8 with confirmed disease), there was high use of fluoroquinolones (levofloxacin, 21; moxifloxacin, 10; ofloxacin, 6) and carbapenems (imipenem, 11; meropenem, 6). Median CSF total concentrations of levofloxacin at 2 and 6h were 1.34mg/L and 3.36mg/L with adjusted CSF/serum ratios of 0.41 and 0.63, respectively. For moxifloxacin, the median CSF total concentrations at 2 and 6h were 0.78mg/L and 1.02mg/L with adjusted CSF/serum ratios of 0.44 and 0.62. Serum and CSF concentrations of moxifloxacin were not affected by rifampin use. Among the 76 CSF samples measured for carbapenem concentrations, 79% were undetectable or below the limit of detection. Conclusion: Fluoroquinolones demonstrated high CSF penetration indicating their potential usefulness for the treatment of TBM. Carbapenems had lower than expected CSF concentrations.

Boston Febrile Infant Algorithm 2.0: Improving Care of the Febrile Infant 1-2 Months of Age.

The algorithm's risk stratification was revised based on the expert review of evidence regarding test performance of PCT for IBI in febrile infants. With the revision, routine LP and empiric antibiotics were not recommended for low-risk infants. We used quality improvement strategies to disseminate the revised algorithm and reinforce uptake. The primary outcomes were the proportion of infants undergoing lumbar punctures or receiving antibiotics. Admission rates, 72-hour revisits requiring admission, and missed IBI were monitored as balancing measures. We studied 616 infants including 326 (52.9%), after the implementation of the revised algorithm. LP was performed in 66.2% prerevision and 31.9% postrevision (34.3% absolute reduction, P < 0.001). Antibiotic administration decreased by 26.2% (pre 62.4% to post 36.2%, P < 0.001) and hospitalization rates decreased by 8.1% (P = 0.03). There have been no missed IBIs. Adherence to the pathway led to a sustained reduction in LPs and antibiotic administration for 24 months. A revised pathway with the addition of PCT resulted in a safe, sustained reduction in LPs and reduced antibiotic administration in febrile infants 1-2 months of age.

Clinical presentation and radiological profile of patients presented with stroke between the ages of 15-45 years

Cerebrovascular disease is the most common life threatening neurological disease and is a concern in young patients especially in developing countries. This study aims to identify clinical presentation and radiological profile of patients presented with stroke between the ages of 15-45 years. 50 patients (29 males and 21 females) were included in the study. Detailed history taking and clinical examination were done and neurological deficits were identified. Other than routine investigations lumbar puncture for CSF analysis, electrocardiography, lipid profile, homocysteine levels and CT scan were done for all the patients. Other investigations such as echocardiography, Doppler etc. were done as clinically indicated. Decreased consciousness 34% [90%CI (22.98-45.02%)], VIIth cranial nerve involvement 54%[90%CI (42.41-65.59%)] and hemiparesis 60% [90%CI (48.60-71.40%)] were the clinical features seen. CT findings revealed ischemia 70% [90%CI (59.34-80.66%)], hemorrhage 20% [90%CI (10.7-29.3%)] and cortical venous thrombosis 10% [90%CI (3.02-16.98%)].

Cycloserine and Linezolid for Tuberculosis Meningitis: Pharmacokinetic Evidence of Potential Usefulness.

The ability of antituberculosis drugs to cross the blood-brain barrier and reach the central nervous system is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed antituberculosis drugs to penetrate into the cerebrospinal fluid (CSF). We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi, Georgia, from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration. A total of 17 patients treated for TBM (8 with confirmed disease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4), and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delamanid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/mL with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/mL at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not affected by rifampin coadministration. Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment, whereas the utility of bedaquiline, delamanid, and clofazimine is uncertain given their low CSF penetration.

Association of Cigarette Smoking With Male Cognitive Impairment and Metal Ions in Cerebrospinal Fluid

Objective: Cigarette smoking might accelerate cognitive impairment; however, this has never been investigated using human cerebrospinal fluid (CSF). We conducted this study to investigate the association between cigarette smoking and cognitive impairment through metal ions in CSF.Methods: We obtained 5-ml CSF samples from routine lumbar puncture procedures in patients undergoing anterior cruciate ligament reconstruction before surgery in China. A total of 180 Chinese males were recruited (80 active smokers and 100 non-smokers). We measured specific cigarette-related neurotoxic metal ions in CSF, including iron, copper, zinc, lead, aluminum, and manganese. Sociodemographic data and history of smoking were obtained. The Montreal Cognitive Assessment (MoCA) was applied.Results: Active smokers had fewer years of education (11.83 ± 3.13 vs. 13.17 ± 2.60, p = 0.01), and higher age (33.70 ± 10.20 vs. 29.76 ± 9.58, p = 0.01) and body mass index (25.84 ± 3.52 vs. 24.98 ± 4.06, p =0.03) than non-smokers. Compared to non-smokers, active smokers had significantly higher CSF levels of iron, zinc, lead, and aluminum and lower MoCA scores (all p < 0.05). Average daily numbers of cigarettes smoked negatively correlated with the MoCA scores (r = −0.244, p = 0.048). In young smokers, CSF manganese levels negatively correlated with MoCA scores (r = −0.373, p = 0.009).Conclusions and Relevance: Cigarette smoking might be associated with male cognitive impairment, as shown by lower MoCA scores and higher levels of CSF iron, zinc, lead, and aluminum in active smokers. This might be early evidence of cigarette smoking accelerating male cognitive impairment.

Flow cytometric analysis of cerebrospinal fluid improves detection of leukaemic blasts in infants with acute lymphoblastic leukaemia.

Infants with acute lymphoblastic leukaemia (ALL) have a high frequency of central nervous system (CNS) involvement. Flow cytometric analysis of cerebrospinal fluid (CSF) was recently demonstrated to be a sensitive method for detecting CNS involvement in childhood ALL. In the present study, CSF from 14 infants was collected at routine lumbar punctures and analysed by multicolour flow cytometry. At initial diagnosis, leukaemic blasts were detected in CSF by flow cytometry in 11 patients (78·6%) compared to seven patients (50%) by cytospin. Larger studies are needed to determine if CSF flow cytometry has prognostic value in infant ALL.

Infant Escherichia coli urinary tract infection: is it associated with meningitis?

ObjectivesDetermine the prevalence of coexisting bacterial meningitis (BM) and sterile cerebrospinal fluid (CSF) with raised white cell count relative to age (‘pleocytosis’) in the presence of Escherichia coli urinary tract...

Utility of Lumbar Puncture in the first episode of Simple Febrile Seizure in Children between 6 to 18 months of age

Introduction: Febrile seizures are the most common seizures occurring in children and areexclusive to childhood. It is the most common pediatric emergency and the most common type ofseizure every pediatrician is dealing with. It accounts for 2.5% of all seizures in children. Despiteprogress in the understanding of febrile seizure and development of consensus statement aboutdiagnostic evaluation and management there exists a diversity of opinion regarding bloodinvestigations, neuro-imaging, Electro Encephalogram (EEG) and the need for routine lumbarpunctures (LP)during a febrile seizure. Aim &amp; objectives: To determine the utility of lumbarpuncture in identifying the group of children aged 6 to18 months having the first episode of feverwith seizures that would benefit from the procedure. Observation: Most common cause of fever infebrile seizures was found to be upper respiratory tract infection (38%) in children followed byAGE(15%). Family history was present in 12.77% of cases of SFS. The most common symptom iscough and cold apart from fever and seizure saw in children. Most common clinical sign wastransient lethargy lasting less than &lt;15 minutes seen in 18% of cases. In 11.7% of cases of SFS adiagnosis of meningitis was made at the time of admission. Out of these only 1 case (2.4%) wassuggestive of meningitis in the age group of 6 to 12 months. Conclusion: Lumbar puncture isnecessary to rule out meningitis in all children between the ages of 6 months to 12 monthspresenting with the first episode of fever with seizure to rule out meningitis.

Bulging fontanelle in febrile infants as a predictor of bacterial meningitis.

It is common practice to perform a lumbar puncture in infants presenting with fever and a bulging fontanelle in order to rule out bacterial meningitis. However, most of these infants have benign, self-limiting diseases. The objective was to determine whether there is an association between bulging fontanelle and bacterial meningitis in febrile infants. This retrospective cohort study included febrile children with a bulging fontanelle who underwent lumbar puncture at Meir Medical Center from 2005 through 2015. A total of 764 children ages 2-18 months underwent lumbar puncture during the study period. Among them, 304 had a bulging fontanelle and fever on evaluation and cerebrospinal fluid pleocytosis was found in 115 (37.8%), including 1 case of bacterial meningitis (0.3%). None of the infants described on admission as appearing well on presentation was found to have bacterial meningitis. Of the 764 children who underwent lumbar puncture, 10 infants were diagnosed with bacterial meningitis, and only one (10%) presented with a bulging fontanelle.Conclusion: The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis. Most causes of a bulging fontanelle in febrile infants are self-limiting diseases. The routine approach of performing a lumbar puncture in febrile infants with a bulging fontanelle should be reconsidered. What is Known: • It is common to perform a lumbar puncture in febrile infants with a bulging fontanelle, to rule out bacterial meningitis. • However, there are only few researches regarding the relationship between bulging fontanelle and bacterial meningitis. What is New: • The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis • The need for routine lumbar puncture in these cases should be reconsidered.

Association of Cigarette Smoking With Cerebrospinal Fluid Biomarkers of Neurodegeneration, Neuroinflammation, and Oxidation

Cigarette smoking has been associated with risk of neurodegenerative disorders, such as Alzheimer disease. The association between smoking and biomarkers of changes in human cerebrospinal fluid (CSF) is not fully understood. To investigate the association of cigarette smoking with CSF biomarkers of neurodegeneration, neuroinflammation, oxidation, and neuroprotection. In this case-control study of 191 adult men in China, biomarkers in the CSF of participants with and without significant cigarette exposure were examined. Participants who did not smoke and had no history of substance use disorder or dependence were assigned to the nonsmoking group. The active smoking group included participants who consumed at least 10 cigarettes per day for 1 year. Five-milliliter samples of CSF were obtained from routine lumbar puncture conducted before anterior cruciate ligament reconstruction surgery. Data collection took place from September 2014 to January 2016, and analysis took place from January to February 2016. Cigarette smoking. CSF levels of β-amyloid 42 (Aβ42), which has diagnostic specificity for Alzheimer disease, tumor necrosis factor alpha (TNFα), brain-derived neurotrophic factor (BDNF), total superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured. Sociodemographic data and history of smoking were obtained. Of 191 participants, 87 (45.5%) were included in the active smoking group and 104 (54.4%) in the nonsmoking group. Compared with the active smoking group, the nonsmoking group was younger (mean [SD] age, 34.4 [10.5] years vs 29.6 [9.5] years; P = .01), had more education (mean [SD] duration of education, 11.9 [3.1] years vs 13.2 [2.6] years; P = .001), and had lower body mass index (mean [SD], 25.9 [3.6] vs 24.9 [4.0]; P = .005). Comparing the nonsmoking group with the smoking group, mean (SD) CSF levels of Aβ42 (38.0 [25.9] pg/mL vs 52.8 [16.5] pg/mL; P < .001) and TNFα (23.0 [2.5] pg/mL vs 28.0 [2.0] pg/mL; P < .001) were significantly lower, while BDNF (23.1 [3.9] pg/mL vs 13.8 [2.7] pg/mL; P < .001), total SOD (15.7 [2.6] U/L vs 13.9 [2.4] U/L; P < .001), total NOS (28.3 [7.2] U/L vs 14.7 [5.6] U/L; P < .001), inducible NOS (16.0 [5.4] U/L vs 10.3 [2.7] U/L; P < .001), and constitutive NOS (12.4 [6.9] U/mL vs 4.4 [3.9] U/mL) were higher. In addition, in participants in the smoking group who were aged 40 years or older, total SOD levels were negatively correlated with Aβ42 levels (r = -0.57; P = .02). In those who smoked at least 20 cigarettes per day, TNFα levels were positively correlated with Aβ42 levels (r = 0.51; P = .006). The association of TNFα with Aβ42 production was stronger than that of total SOD with Aβ42 production (z = -4.38; P < .001). This case-control study found that cigarette smoking was associated with at-risk biomarkers for Alzheimer disease, as indicated by higher Aβ42 levels, excessive oxidative stress, neuroinflammation, and impaired neuroprotection found in the CSF of participants in the active smoking group.

Febrile Seizure Team-based Learning.

This modified team-based learning (mTBL) is designed for junior and senior emergency medicine and pediatric residents. Febrile seizures are the most common cause of seizures in children under 5 years old and are frequently evaluated in the emergency department.1,2 Febrile seizures can be frightening for parents to witness and often necessitate extensive parental reassurance and education by the emergency medicine (EM) provider. Most febrile seizures are brief, do not require a broad workup, and have a benign prognosis. With introduction of conjugate vaccines for Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae in the United States in 1987 and 2000 respectively, the incidence of bacterial meningitis is low, but still present.3-7 The most recent American Academy of Pediatrics practice guidelines no longer recommend routine lumbar puncture on children presenting with simple febrile seizures.2 A review of the current literature shows that bacterial meningitis in children after a complex febrile seizure is unexpected when the clinical examination is not suggestive of meningitis or encephalitis.5-8 The goal of this mTBL is for residents to feel comfortable counseling parents about their child currently in the emergency department and the future risk of recurrence. The second goal is for residents to identify which patients presenting with fever and a seizure do require workup beyond simply identifying the source of the fever. By the end of this educational session, the learner will:List the characteristics of a simple febrile seizure.Discuss the management of a child with a simple vs. complex febrile seizure.Discuss the risk factors that correlate with an increased risk of a subsequent febrile seizure.Determine when a lumbar puncture should be considered in a febrile child with a seizure.Identify when to give anti-epileptics and construct an algorithm for their use.Discuss with parents, provide education and return precautions. This didactic session is a mTBL. The classic learner responsible content (LRC) has been omitted and a short PowerPoint presentation is given to start the session before the individual and group readiness assessment tests. A post-TBL survey was given to each participant. A Likert scale was used to assess each participant's assessment for the learning session in the following categories: overall, context, quality, and speaker feedback. They were also given fields to enter ways in which they would improve their practice after this learning exercise and suggestions they had for improving the current educational opportunity. In the pilot session of this mTBL, 4 out of 11 participants (EM residents and pediatric emergency medicine [PEM] fellows) completed the post-TBL survey. Overall, this session was rated as "outstanding" (Likert 5/5) by 1 and "excellent" (Likert 4/5) by 3 for a weighted average of 4.25. All participants completing the survey found the activity "highly relevant," "very engaging," and wanted to repeat the activity in the future. Negative feedback consisted of wanting a video of a child having a seizure to be played and having a more interactive PowerPoint portion of the session like the interaction in the readiness assessment tests and group application exercise. Overall the content was effective as evidenced by the list of ways residents said they would improve their practice on the post-TBL survey. In the future, I would extend the session from 60 minutes to 90 minutes to allow for more time for the group application exercise and discussion of answers. I found this to be an enjoyable, highly interactive experience with high engagement of the residents during the session. Simple febrile seizures, complex febrile seizures, seizure with fever, meningitis, lumbar puncture, status epilepticus.

Machine Learning To Predict Serious Bacterial Infections in Young Febrile Infants.

Recent decision rules for the management of febrile infants support the identification of infants at higher risk of serious bacterial infections (SBIs) without the performance of routine lumbar puncture. We derive and validate a model to identify febrile infants ≤60 days of age at low risk for SBIs using supervised machine learning approaches. We conducted a secondary analysis of a multicenter prospective study performed between December 2008 and May 2013 of febrile infants. Our outcome was SBI, (culture-positive urinary tract infection, bacteremia, and/or bacterial meningitis). We developed and validated 4 supervised learning models: logistic regression, random forest, support vector machine, and a single-hidden layer neural network. A total of 1470 patients were included (1014 >28 days old). One hundred thirty-eight (9.3%) had SBIs (122 urinary tract infections, 20 bacteremia, and 8 meningitis; 11 with concurrent SBIs). Using 4 features (urinalysis, white blood cell count, absolute neutrophil count, and procalcitonin), we demonstrated with the random forest model the highest specificity (74.9, 95% confidence interval: 71.5%-78.2%) with a sensitivity of 98.6% (95% confidence interval: 92.2%-100.0%) in the validation cohort. One patient with bacteremia was misclassified. Among 1240 patients who received a lumbar puncture, this model could have prevented 849 (68.5%) such procedures. We derived and internally validated a supervised learning model for the risk-stratification of febrile infants. Although computationally complex, lacking parameter cutoffs, and in need of external validation, this strategy may allow for reductions in unnecessary procedures, hospitalizations, and antibiotics while maintaining excellent sensitivity.

Neonates With Urinary Tract Infection: Is a Lumbar Puncture Always Indicated?

Our objectives were to determine the prevalence of and to identify risk factors for coexisting bacterial meningitis (BM) in neonates with urinary tract infection (UTI). A cross-sectional study was conducted at pediatric emergency department of a tertiary teaching hospital from 2001 to 2017. Infants <29 days of age with UTI (≥10,000 colony-forming units/mL of a single pathogen from a catheterized specimen in association with positive urinalysis) were included. Definite BM was defined as growth of a single bacterial pathogen from a cerebrospinal fluid (CSF) sample and probable BM as (1) positive blood culture with CSF pleocytosis and treatment consistent with BM or (2) antibiotic pretreatment before lumbar puncture, CSF pleocytosis and treatment consistent with BM. Univariate testing was used to identify possible risk factors associated with BM. Receiver operating characteristics curves were constructed for the laboratory markers associated with BM. Three hundred seventy-one infants were included. Five [1.3%; 95% confidence interval (CI): 0.6%-3.1%] had BM: 4 definite BM and 1 probable BM. Risk factors detected for BM were classified as not being well-appearing and a procalcitonin value ≥0.35 ng/mL [sensitivity of 100% (95% CI: 56.6%-100%) and negative predictive value of 100% (95% CI: 96.1%-100%)]. Coexisting BM occurs uncommonly in neonates with UTI. Well-appearing neonates with UTI and procalcitonin value <0.35 ng/mL were at very low risk for BM; avoiding routine lumbar puncture in these patients should be considered.

Acute Myeloid Leukemia with High Risk Features: Routine Central Nervous System Evaluation May be Beneficial

Objective : Central nervous system (CNS) involvement is a known phenomenon of acute lymphoblastic leukemia. However little is known about the incidence of CNS involvement in acute myeloid leukemia (AML) as routine lumbar punctures are not done if patients are asymptomatic at diagnosis. Our practice has been to obtain lumbar puncture (LP) at or after complete remission (CR) for patients that present with any one of the following high risk features;hyperleukocytosis with WBC &gt;10,000 or blastic crisis, extramedullary disease,monocytic differentiation. Methods: We reviewed our leukemia database at Mayo Clinic to determine the incidence of CNS involvement in patients with high risk features after due IRB approval. We also compared baseline demographic characteristics, blood counts, cytogenetic risk groups, presence of extramedullary disease, relapse rate ,transplant rate and overall survival (OS) among patients with and without CNS involvement. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Results: 298 patients with AML were identified with presence of at least 1 risk factor for CNS involvement. The results of LP were only available for 126 (42%) patients. The overall incidence of CNS involvement was 12% (15/126, figure 1). Among the patients with positive disease 3 had CSF examination at diagnosis prior to CR due to the presence of CNS myeloid sarcoma (n=2) and ambiguous lineage myeloid leukemia and were excluded from further evaluation. The incidence of CSF involvement at CR1 was 9.7% (12/123). All patient with CNS positive disease received intrathecal chemotherapy with alternating cytarabine and methotrexate until they cleared their blast and additional 2-4 treatments as per treating physician's discretion .The CNS positive and negative patients were compared and did not show any statistical difference in age, gender, presence of extramedullary disease ,cytogenetic risk group, relapse rate and transplant rate as shown in table1. Molecular data was not available in most of the patients and hence was not included for analysis. The median OS was significantly lower among patients with CNS involvement compared to absence of CNS involvement but was not statistically significant likely due to small sample size (3.9 vs12.8 years (p=0.2), figure 2). The overall CNS relapse rate in patients who did not have a LP done at CR was 5.8%(10/172). Conclusions : CNS evaluation should be done in AML patients with high risk features before declaring CR. CNS disease portends overall a poor prognosis with impaired overall survival and high relapse rate. However the sample size was small and true incidence of CNS disease will need routine diagnostic LP in all high risk patients. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

Incidence and clinico-demographic characteristics of neonatal meningitis in clinically suspected sepsis: an observational study

Background: Authors objective was to study the incidence and risk factors for meningitis in neonates with clinical suspicion of sepsis in Neonatal Intensive Care Unit (NICU) of tertiary care hospital of Mumbai, India.Methods: This descriptive observational study enrolled Consecutive 92 patients of either sex with suspected neonatal sepsis admitted in NICU of Tertiary Care Hospital. All neonates admitted to NICU with clinical suspicion of sepsis or developing signs of sepsis during NICU stay were included in study. Exclusion criteria were 1.Neonates with hemodynamic instability 2.major congenital malformations 3.contraindication or no willingness for Lumber puncture (LP ) 4.neonates who have received intravenous antibiotics for more than 24 hours elsewhere.Standard data collection form was used to collect all demographic data and clinical characteristics of neonates.Results: Incidence of meningitis in study population was 7.6%. Cases of meningitis in study population had mean birth weight 1.91 kg, 71.43% were preterm, 57.14% vaginaly delivered, 42.86% by LSCS, Premature rupture of membrane (PROM) observed in 28.57% cases. Meconium stained liquor in 42.86% cases and foul smelling liquor in 28.57% cases observed. 42.86% cases required resuscitation and 28.57% received surfactant therapy. Poor feeding (100%), lethargy (85.71%), weak cry (85.71%) and tachypnea (50.58%). Retractions (85.71%), Grunting (57.14%) and Nasal flaring (42.86%) were clinical presentation. Lab findings in a case of meningitis: mean Hemoglobin (Hb) 15.22 gm%, Leukopenia (28.57%), Leukocytosis 28.57%, Absolute Neutrophil count (ANC) &lt;1800 (28.57%), Thrombocytopenia 42.85%, blood culture positive (28.57%) hypoglycemia (28.57%), CSF white cell count (124.57cells/ml.), mean CSF protein level (60 mg/dl.) Mean CSF glucose level (40.86 mg/dl.) CSF culture was positive in two cases of meningitis.Conclusions: Authors study highlights the diagnostic utility of routine lumbar puncture in neonates with clinically suspected sepsis.

Assessment of the necessity of routine lumber puncture among children with fever and convulsions

The routine investigation of doing lumbar puncture in patient with febrile convulsion is increasing practiced in many hospital.&#x0D; Objectives: &#x0D; The aim of this study was to assess the necessity of routine lumbar puncture (LP) to diagnose meningitis in children who present with fever and convulsions.&#x0D; Methods:&#x0D; This is an observational, cross-sectional, hospital-based study, carried out in Mohammed AL-Amin Hamid pediatrics hospital-Omdurman Sudan, during the period from the first of January through 31 July 2018. It involved all (146) children aged 5 months to 6years , who presented with fever and convulsions, undergone lumbar puncture, and parents signed written informed consents. Children with known neurological diseases were excluded from this study. Data collected included, age, gender, convulsions type and duration, post-ictal state, routine vaccination status, general condition, recent antibiotics use, past history of fever and convulsions, temperature degree, signs of meningeal irritation, and conscious level. Data were analyzed by Statistical Package for Social Sciences (SPSS) version 23.&#x0D; Results:&#x0D; The result revealed that total number of 146 children, male were 62% (n=91), female were 38% (n=55). 5-11 months 35.6% (n=52) 1-3years 43.8% (n=64), and 4-6 years 20.6% (n=30). About 80% of the patients were younger than 4 years of age. Convulsion was generalized in 97.9%, lasted less than 15 minutes in 99.3%, spontaneously aborted in 94.5%, post-ictal state was brief in 88.4%, first attack in 98.6%, and there was no family history in 97.3%,p=0.000. There was no neck stiffness and photophobia in 92.5% and 98.6% respectively, p=0.000. Patients general condition were well in 76.7% and toxic in 23.3%. Cerebrospinal fluids (CSF) color was clear in 97% and turbid in 3% of patients. CSF white cells was less than 5 in 93.8%, and CSF sugar and protein were normal in 97.3% and 96.6 % respectively, p=0.000. CSF culture was negative for all patients, and almost all (97%, n=141) of the patients were diagnosed as febrile convulsions and sent home, compared to 3% (n=5) who were diagnosed clinically as meningitis.&#x0D; Conclusion:&#x0D; This study revealed that, CSF culture was negative for all patients, and almost all were diagnosed as febrile convulsions. However, 5 patients were diagnosed clinically as meningitis. Hence, this findings, challenge the routine lumbar puncture in children who present with fever and convulsion.