The Association between Prolonged Antibiotic Use in Culture Negative Infants and Length of Hospital Stay and Total Hospital Costs.

OBJECTIVE: This study aimed to determine if prolonged antibiotic use at birth in neonates with a negative blood culture increases the total cost of hospital stay. STUDY DESIGN: This was a retrospective study performed at a 60-bed level IV neonatal intensive care unit. Neonates born <30 weeks of gestation or <1,500 g between 2016 and 2018 who received antibiotics were included. A multivariate linear regression analysis was conducted to determine if clinical factors contributed to increased hospital cost or length of stay. RESULTS: In total, 190 patients met inclusion criteria with 94 infants in the prolonged antibiotic group and 96 in the control group. Prolonged antibiotic use was associated with an increase length of hospital stay of approximately 31.87 days, resulting in a $69,946 increase in total cost of hospitalization. CONCLUSION: Prolonged antibiotics in neonates with negative blood culture were associated with significantly longer hospital length of stay and increased total cost of hospitalization. KEY POINTS: · Prolonged antibiotic use at birth is associated with prolonged hospital stay.. · Prolonged antibiotic use at birth is associated with increased cost of hospitalization.. · Prolonged antibiotic use at birth is associated with increased days on total parenteral nutrition.. · Prolonged antibiotic use at birth is associated with increased subsequent courses of antibiotics..

Opioid-Free Analgesia for Supratentorial Craniotomies: A Systematic Review.

BACKGROUND: Post-craniotomy pain can be severe and is often undermanaged. Opioids can interfere with neurological monitoring and are associated with adverse effects. This systematic review aimed to identify measures of opioid-free analgesia and compare their effectiveness with opioid analgesia for post-craniotomy pain in patients with supratentorial tumors. METHODS: EMBASE, MEDLINE, and Cochrane databases were searched from their inception to February 14, 2017, for randomized controlled trials (RCTs) evaluating opioid versus non-opioid analgesia post-supratentorial craniotomy. Two reviewers independently carried out study selection and data extraction. Risk of bias assessment was performed using the Cochrane Collaboration's tool. Outcomes were pain control (changes to pain scores or use of rescue analgesia) and adverse effects. Considering the number of studies and heterogeneity, a narrative synthesis was done without pooling and results were summarized using tables. Non-opioids were assessed for the potential to be equivalent to opioid-based analgesics for pain relief and adverse effects. RESULTS: Of 467 RCTs, 4 met our inclusion criteria (n = 186 patients). Patients with scalp blocks (2 RCTs) had less post-operative nausea and vomiting (PONV), but scalp block was not superior to morphine for analgesia. Acetaminophen (1 RCT) was less likely to induce PONV but provided inadequate pain relief compared to morphine and sufentanil. Dexmedetomidine (1 RCT) was not superior to remifentanil for analgesia although it delayed time to rescue analgesia. CONCLUSIONS: Limited evidence suggests that scalp blocks and dexmedetomidine have the potential to eliminate the need for opioid analgesia. Multimodal analgesia should be considered as significant opioid-sparing effects have been shown.

Analgésie sans opioïdes dans les craniotomies supratentorielles: revue systématique. Contexte: La douleur post-craniotomie peut être sévère et n'est souvent pas maintenue. Les opioïdes peuvent interférer avec la surveillance neurologique et sont associés à des effets indésirables. Cette revue systématique visait à identifier les mesures d'analgésie sans opioïdes et à comparer leur efficacité à celle des analgésiques opioïdes pour le traitement de la douleur post-craniotomie chez les patients atteints de tumeurs supratentorielles. Méthodes: Les bases de données EMBASE, MEDLINE et Cochrane ont été explorées depuis leur création jusqu'au 14 février 2017 dans le cadre d'essais contrôlés randomisés (ECR) évaluant l'analgésie opioïde ou non opioïde après la craniotomie supratentorielle. Deux examinateurs ont indépendamment sélectionné les études et extrait les données. L'évaluation du risque de biais a été réalisée à l'aide de l'outil Cochrane Collaboration. Les résultats ont été un contrôle de la douleur (modification des scores de douleur ou l'utilisation d'une analgésie de secours) et des effets indésirables. Compte tenu du nombre d'études et de l'hétérogénéité, une synthèse narrative a été réalisée sans regroupement et les résultats ont été résumés à l'aide de tableaux. Les non-opioïdes ont été évalués pour leur potentiel équivalent aux analgésiques à base d'opioïdes pour le soulagement de la douleur et les effets indésirables. Résultats: Sur 467 ECR, 4 répondaient à nos critères d'inclusion (n = 186 patients). Les patients avec des blocs de cuir chevelu 14 (2 ECR) avaient moins de nausées et de vomissements postopératoires (NVPO), mais le bloc de cuir chevelu n'était pas supérieur à la morphine pour l'analgésie. L'acétaminophène (1 ECR) était moins susceptible d'induire des NVPO, mais ne soulageait pas suffisamment la douleur par rapport à la morphine et au sufentanil. La dexmédétomidine (1 ECR) n'était pas supérieure au rémifentanil pour l'analgésie, bien qu'elle ait retardé le délai de récupération de l'analgésie. Conclusions: Des preuves limitées suggèrent que les blocs du cuir chevelu et la dexmédétomidine pourraient éliminer le besoin d'une analgésie opioïde. Une analgésie multimodale doit être considérée, car des effets importants, qui permettent d'épargner les opioïdes, ont été démontrés.

Copy number variation and selection during reprogramming to pluripotency.

The mechanisms underlying the low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells are poorly understood. There is a clear need to study whether the reprogramming process itself compromises genomic integrity and, through this, the efficiency of iPS cell establishment. Using a high-resolution single nucleotide polymorphism array, we compared copy number variations (CNVs) of different passages of human iPS cells with their fibroblast cell origins and with human embryonic stem (ES) cells. Here we show that significantly more CNVs are present in early-passage human iPS cells than intermediate passage human iPS cells, fibroblasts or human ES cells. Most CNVs are formed de novo and generate genetic mosaicism in early-passage human iPS cells. Most of these novel CNVs rendered the affected cells at a selective disadvantage. Remarkably, expansion of human iPS cells in culture selects rapidly against mutated cells, driving the lines towards a genetic state resembling human ES cells.

Reoperation in adult patients with recurrent glioblastoma: A matched cohort analysis.

Background: Despite maximal safe cytoreductive surgery and postoperative adjuvant therapies, glioblastoma (GBM) inevitably recurs and leads to deterioration of neurological status and eventual death. There is no consensus regarding the benefit of repeat resection for enhancing survival or quality of life in patients with recurrent GBM. We aimed to examine if reoperation for GBM recurrence incurs a survival benefit as well as examine its complication profile. Methods: We performed a single-center retrospective chart review on all adult patients who underwent resection of supratentorial GBM between January 1, 2008 and December 1, 2013 at our center. Patients with repeat resection were manually matched for age, sex, tumor location, and Karnofsky Performance Status (KPS) with patients who underwent single resection to compare overall survival (OS), and postoperative morbidity. Results: Of 237 patients operated with GBM, 204 underwent single resection and 33 were selected for repeat surgical resections. In a matched analysis there was no difference in the OS between groups (17.8 ± 17.6 months vs 17 ± 13.5 months, P = .221). In addition, repeat surgical resection had a higher rate of postoperative neurological complications compared to the initial surgery. Conclusions: When compared with matched patients who underwent a single surgical resection, patients undergoing repeat surgical resection did not show significant increase in OS and may have incurred more neurological complications related to the repeat resection. Further studies are required to assess which patients would benefit from repeat surgical resection and optimize timing of the repeat resection in selected patients.

Biopsy Versus Subtotal Versus Gross Total Resection in Patients with Low-Grade Glioma: A Systematic Review and Meta-Analysis.

BACKGROUND: The role of the extent of surgical resection (EOR) in clinical outcomes for patients with low-grade glioma requires further examination. The goal of the present study was to evaluate the association between variable degrees of EOR and clinical outcomes for patients with low-grade glioma. METHODS: We conducted a systematic review and meta-analysis and searched databases for reports of low-grade glioma EOR. Eligible studies compared patient outcomes, including ≥2 categories of EOR (biopsy, resection of any extent, subtotal resection [STR], or gross total resection [GTR]). Treatment effects were evaluated using pooled estimates, mean differences, or risk ratios (RRs) with corresponding 95% confidence intervals (CIs) using random effects modeling. RESULTS: Our literature search yielded 60 studies with 13,289 patients. Pooled estimates of overall survival (OS) showed an increase from 3.79 years in the biopsy group to 6.68 years in STR to 10.65 years in GTR. OS was favorable with resection of any extent compared with (mean difference, 3.24; 95% CI, 0.64-5.84; P = 0.015). Pooled estimates of seizure control showed an improvement from 47.8% with biopsy to 54.2% with STR and 81.0% with GTR. Compared with STR, GTR delayed malignant transformation (RR, 0.43; 95% CI, 0.20-0.93; P = 0.032), without increasing postoperative mortality (RR, 0.38; 95% CI, 0.07-1.97; P = 0.250) or morbidity (RR, 1.22; 95% CI, 0.65-2.28; P = 0.540). CONCLUSION: Among patients with low-grade gliomas, greater degrees of safe EOR were associated with longer OS and progression-free survival, better seizure control, and delayed malignant transformation, without increasing mortality or morbidity.

Acute, delayed and chronic remote ischemic conditioning is associated with downregulation of mTOR and enhanced autophagy signaling.

BACKGROUND: Remote ischemic conditioning (RIC), induced by brief periods of limb ischemia has been shown to decrease acute myocardial injury and chronic responses after acute coronary syndromes. While several signaling pathways have been implicated, our understanding of the cardioprotection and its underlying mediators and mechanisms remains incomplete. In this study we examine the effect of RIC on pro-autophagy signaling as a possible mechanism of benefit. METHODS AND RESULTS: We examined the role of autophagy in the acute/first window (15 minutes after RIC), delayed/second window (24 hours after RIC) and chronic (24 hours after 9 days of repeated RIC) phases of cardioprotection. C57BL/6 mice (N = 69) were allocated to each treatment phase and further stratified to receive RIC, induced by four cycles of 5 minutes of limb ischemia followed by 5 minutes of reperfusion, or control treatment consisting solely of handling without transient ischemia. The groups included, group 1 (1W control), group 2 (1W RIC), group 3 (2W control), group 4 (2W RIC), group 5 (3W control) and group 6 (3W RIC). Hearts were isolated for assessment of cardiac function and infarct size after global ischemia using a Langendorff preparation. Infarct size was reduced in all three phases of cardioprotection, in association with improvements in post-ischemic left ventricular end diastolic pressure (LVEDP) and developed pressure (LVDP) (P<0.05). The pattern of autophagy signaling varied; 1W RIC increased AMPK levels and decreased the activation of mammalian target of rapamycin (mTOR), whereas chronic RIC was associated with persistent mTOR suppression and increased levels of autophagosome proteins, LC3II/I and Atg5. CONCLUSIONS: Cardioprotection following transient ischemia exists in both the acute and delayed/chronic phases of conditioning. RIC induces pro-autophagy signaling but the pattern of responses varies depending on the phase, with the most complete portfolio of responses observed when RIC is administered chronically.