Efficacy of different routes of acetaminophen administration for postoperative pain in children: a systematic review and network meta-analysis.

PURPOSE: Acetaminophen is the most common drug used to treat acute pain in the pediatric population, given its wide safety margin, low cost, and multiple routes for administration. We sought to determine the most efficacious route of acetaminophen administration for postoperative acute pain relief in the pediatric surgical population. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) that included children aged between 30 days and 17 yr who underwent any type of surgical procedure and that evaluated the analgesic efficacy of different routes of administration of acetaminophen for the treatment of postoperative pain. We searched MEDLINE, CENTRAL, Embase, CINAHL, LILACs, and Google Scholar databases for trials published from inception to 16 April 2023. We assessed the risk of bias in the included studies using the Cochrane Risk of Bias 1.0 tool. We performed a frequentist network meta-analysis using a random-effects model. Our primary outcome was postoperative pain using validated pain scales. RESULTS: We screened 2,344 studies and included 14 trials with 829 participants in the analysis. We conducted a network meta-analysis for the period from zero to two hours, including six trials with 496 participants. There was no evidence of differences between intravenous vs rectal routes of administration of acetaminophen (difference in means, -0.28; 95% confidence interval [CI], -0.62 to 0.06; very low certainty of the evidence) and intravenous vs oral acetaminophen (difference in means, -0.60; 95% CI, -1.20 to 0.01; low certainty of the evidence). For the comparison of oral vs rectal routes, we found evidence favouring the oral route (difference in means, -0.88; 95% CI, -1.44 to -0.31; low certainty of the evidence). Few trials reported secondary outcomes of interest; when comparing the oral and rectal routes in the incidence of nausea and vomiting, there was no evidence of differences (relative risk, 1.20; 95% CI, 0.81 to 1.78). CONCLUSION: The available evidence on the effect of the administration route of acetaminophen on postoperative pain in children is very uncertain. The outcomes of postoperative pain control and postoperative vomiting may differ very little between the oral and rectal route. Better designed and executed RCTs are required to address this important clinical question. STUDY REGISTRATION: PROSPERO (CRD42021286495); first submitted 19 November 2021.

RéSUMé: OBJECTIF: Compte tenu de sa large marge de sécurité, de son faible coût et de ses multiples voies d'administration, l'acétaminophène est le médicament le plus couramment utilisé pour traiter la douleur aiguë dans la population pédiatrique. Nous avons cherché à déterminer la voie d'administration d'acétaminophène la plus efficace pour le soulagement de la douleur aiguë postopératoire dans la population chirurgicale pédiatrique. MéTHODE: Nous avons réalisé une revue systématique d'études randomisées contrôlées (ERC) qui ont inclus des enfants âgé·es de 30 jours à 17 ans ayant bénéficié de n'importe quel type d'intervention chirurgicale et qui ont évalué l'efficacité analgésique de différentes voies d'administration d'acétaminophène pour le traitement de la douleur postopératoire. Nous avons mené des recherches dans les bases de données MEDLINE, CENTRAL, Embase, CINAHL, LILAC et Google Scholar pour en tirer les études publiées depuis leur création jusqu'au 16 avril 2023. Le risque de biais dans les études incluses a été évalué à l'aide de l'outil de Risque de biais 1.0 de Cochrane. Nous avons réalisé une méta-analyse de réseau fréquentiste à l'aide d'un modèle à effets aléatoires. Notre critère d'évaluation principal était la douleur postopératoire mesurée à l'aide d'échelles de douleur validées. RéSULTATS: Nous avons passé en revue 2344 études et inclus 14 études incluant un total de 829 enfants dans l'analyse. Nous avons mené une méta-analyse en réseau pour une période allant de zéro à deux heures, comprenant six études avec 496 participant·es. Il n'y avait aucune preuve de différences entre les voies d'administraion intraveineuse vs rectale de l'acétaminophène (différence de moyennes, −0,28; intervalle de confiance [IC] à 95 %, −0,62 à 0,06; très faible certitude des données probantes) et entre les voies intraveineuse vs orale (différence de moyennes, −0,60; IC 95 %, −1,20 à 0,01; faible certitude des données probantes). Pour la comparaison des voies orale vs rectale, nous avons trouvé des données probantes en faveur de la voie orale (différence de moyennes, −0,88; IC 95 %, −1,44 à −0,31; faible degré de certitude des données probantes). Peu d'études ont rapporté des résultats secondaires d'intérêt; en comparant les voies orale et rectale dans l'incidence des nausées et des vomissements, il n'y avait aucune preuve de différences (risque relatif, 1,20; IC 95 %, 0,81 à 1,78). CONCLUSION: Les données probantes disponibles sur l'effet de la voie d'administration de l'acétaminophène sur la douleur postopératoire chez les enfants sont très incertaines. Les résultats de contrôle de la douleur postopératoire et de vomissements postopératoires peuvent différer très peu entre la voie orale et la voie rectale. Des ERC mieux conçues et mieux exécutées sont nécessaires pour répondre à cette importante question clinique. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021286495); première soumission le 19 novembre 2021.

Sepsis-related outcomes of patients with Philadelphia-negative myeloproliferative neoplasms.

We analyzed the National Inpatient Sample (NIS) database to study the sepsis-related outcomes in patients with Philadelphia negative myeloproliferative neoplasms (MPN). A total of 82,087 patients were included, most had essential thrombocytosis (83.7%), followed by polycythemia vera (13.7%), and primary myelofibrosis (2.6%). Sepsis was diagnosed in 15,789 (19.2%) patients and their mortality rate was higher than non-septic patients (7.5% vs 1.8%; P<.001). Sepsis was the most significant risk factor of mortality (aOR, 3.84; 95% CI, 3.51-4.21), others included liver disease (aOR, 2.42; 95% CI, 2.11-2.78), pulmonary embolism (aOR, 2.26; 95% CI, 1.83-2.80), cerebrovascular disease (aOR, 2.05; 95% CI, 1.81-2.33), and myocardial infarction (aOR, 1.73; 95% CI, 1.52-1.96).

Sepsis-Related Outcomes of Patients with Philadelphia-Negative Myeloproliferative Neoplasms.

We analyzed the National Inpatient Sample (NIS) database to study the sepsis-related outcomes in patients with Philadelphia negative myeloproliferative neoplasms (MPN). A total of 82,087 patients were included, most had essential thrombocytosis (83.7%), followed by polycythemia vera (13.7%), and primary myelofibrosis (2.6%). Sepsis was diagnosed in 15,789 (19.2%) patients and their mortality rate was higher than nonseptic patients (7.5% vs 1.8%; p < .001). Sepsis was the most significant risk factor of mortality (aOR, 3.84; 95% CI, 3.51-4.21), others included liver disease (aOR, 2.42; 95% CI, 2.11-2.78), pulmonary embolism (aOR, 2.26; 95% CI, 1.83-2.80), cerebrovascular disease (aOR, 2.05; 95% CI, 1.81-2.33), and myocardial infarction (aOR, 1.73; 95% CI, 1.52-1.96).

Renal Manifestations and their Association with Mortality and Length of Stay in COVID-19 Patients at a Safety-net Hospital.

Background: Renal involvement in COVID-19 leads to severe disease and higher mortality. We study renal parameters in COVID-19 patients and their association with mortality and length of stay in hospital. Methods: A retrospective study (n=340) of confirmed COVID-19 patients with renal involvement determined by the presence of acute kidney injury. Multivariate analyses of logistic regression for mortality and linear regression for length of stay (LOS) adjusted for relevant demographic, comorbidity, disease severity, and treatment covariates. Results: Mortality was 54.4% and mean LOS was 12.9 days. For mortality, creatinine peak (OR:35.27, 95% CI:2.81, 442.06, p<0.01) and persistent renal involvement at discharge (OR:4.47, 95% CI:1.99,10.06, p<0.001) were each significantly associated with increased odds for mortality. Increased blood urea nitrogen peak (OR:0.98, 95%CI:0.97,0.996, p<0.05) was significantly associated with decreased odds for mortality. For LOS, increased blood urea nitrogen peak (B:0.001, SE:<0.001, p<0.01), renal replacement therapy (B:0.19, SE:0.06, p<0.01), and increased days to acute kidney injury (B:0.19, SE:0.05, p<0.001) were each significantly associated with increased length of stay. Conclusion: Our study emphasizes the importance in identifying renal involvement parameters in COVID-19 patients. These parameters are associated with LOS and mortality, and may assist clinicians to prognosticate COVID-19 patients with renal involvement.

Hematologic Involvement as a Predictor of Mortality in COVID-19 Patients in a Safety Net Hospital.

INTRODUCTION: COVID-19 affects the hematologic system. This article evaluated the impact of hematologic involvement of different blood cell line parameters of white blood cells including absolute neutrophil count (ANC), hemoglobin, and platelets in COVID-19 patients and their association with hospital mortality and length of stay (LOS). METHODS: This was a retrospective study of 475 patients with confirmed positive COVID-19 infection and hematologic abnormalities in the metropolitan New York City area. RESULTS: Elevated absolute neutrophil count (OR: 1.20; 95% CI: 1.02-1.42; p < 0.05) increased days of hematologic involvement (OR: 4.44; 95% CI: 1.42-13.90; p < 0.05), and persistence of hematologic involvement at discharge (OR: 2.87; 95% CI: 1.20-6.90; p < 0.05) was associated with higher mortality. Higher hemoglobin at admission (OR: 0.77; 95% CI:0.60-0.98; p < 0.001) and platelets peak (OR: 0.995; 95% CI: 0.992-0.997; p < 0.001) were associated with decreased mortality. Patients with higher white blood cell peak (B = 0.46; SE = 0.07; p < 0.001) and higher hemoglobin at admission (B = 0.05; SE = 0.01; p < 0.001) were associated with higher LOS. Those with higher hemoglobin nadir (B = -0.06; SE = 0.01; p < 0.001), higher platelets nadir (B = -0.001; SE = < 0.001; p < 0.001), and hematologic involvement at discharge or death (B = -0.06; SE = 0.03; p < 0.05) were associated with lower LOS. CONCLUSIONS: These findings can be used by clinicians to better risk-stratify patients with hematologic involvement in COVID-19 and tailor therapies potentially to improve patient outcomes.

Sarcoma del estroma endometrial del ovario. Presentación de un caso y revisión del cuadro clínico-patológico / Endometrial stromal sarcoma of the ovary. A case report and review of the literature

Se presenta el caso de una mujer de 48 años de edad con sarcoma del estroma endometrial en ambos ovarios, con implantes peritoneales, asociado a endometriosis ovárica y uterina, así como diferenciación focal del tumor ovárico con tumor semejante al de los cordones sexuales. Se realizaron reacciones de inmunohistoquímica para los tumores ováricos y su diferenciación a cordones sexuales. Se hace una revisión de la literatura, ilustrando las características morfológicas y se discute los diagnósticos diferenciales(AU)

A case of bilateral ovarian endometrial stromal sarcoma and peritoneal implants associated with ovarian and uterine endometriosis in a 48 year old woman is presented. Focal differentiation into areas of sex-cord stromal tumour were found. Immunohistochemistry for both the ovarian tumour and the sex-cord stromal tumour was carried out. The morphology and differential diagnosis are discussed together with a review of the literature(AU)

Rap1GAP promotes invasion via induction of matrix metalloproteinase 9 secretion, which is associated with poor survival in low N-stage squamous cell carcinoma.

The objective of the current study was to investigate the effects of Rap1GAP on invasion and progression of head and neck squamous cell carcinoma (SCC) and the role of matrix metalloproteinase (MMP) 9 and MMP2 in this process. Rap1GAP functions by switching off Rap1, the Ras-like protein that has been associated with carcinogenesis. Previous findings suggest that Rap1GAP acts as a tumor suppressor protein in SCC by delaying the G(1)-S transition of the cell cycle. However, cells transfected with Rap1GAP exhibit a more invasive phenotype than corresponding vector-transfected control cells. MMP2 and MMP9 are enzymes that mediate SCC invasion via degradation of the extracellular matrix. Using SCC cells transfected with empty vector or Rap1GAP, cell invasion and MMP secretion were determined by Matrigel assays and gelatin zymography, respectively. Rap1GAP up-regulated transcription and secretion of MMP2 and MMP9, as assayed by quantitative reverse transcription-PCR and zymography. Furthermore, chemical and RNA interference blockade of MMP2/MMP9 inhibited invasion by Rap1GAP-transfected cells. Immunohistochemical staining of a human oropharyngeal SCC tissue microarray showed that Rap1GAP and MMP9 expression and staining intensity are correlated (P < 0.0001) and that, in early N-stage lesions of SCC, high MMP9 is prognostic of poor disease-specific survival (P < 0.05). Furthermore, Rap1GAP staining is correlated with MMP2 (P < 0.03). MMP2 in combination with N stage has a prognostic effect on time to indication of surgery at primary site. MMP2 intensity is also positively correlated with T stage (P < 0.015). In conclusion, Rap1GAP inhibits tumor growth but induces MMP2- and MMP9-mediated SCC invasion and tumor progression, suggesting a role for this protein as a biomarker for early N-stage, aggressive SCCs.

Construction and characterization of a bacterial artificial chromosome library of the causal agent of Black Sigatoka fungal leaf spot disease of banana and plantain, Mycosphaerella fijiensis.

A bacterial artificial chromosome library of the causal agent of the Black Sigatoka leaf spot disease of banana and plantain, Mycosphaerella fijiensis, has been constructed using a non-sphaeroplasting technique and characterized using both homologous and heterologous probes. After first and a second size selection of PFGE-fractionated DNA, a ligation was obtained using a 1:4 molar ratio (insert:vector). One hundred random clones were analyzed, and the mean insert size was estimated to be 90 kb. The range of the insert sizes was between 40 and 160 kb. The highest percentage of inserts belonged to the range between 80 and 100 kb; 32% of the inserts had 2 or 3 internal NotI sites. This library consists of 1920 clones, if the genomic size is at least 35 Mb, then this represents 4.9 x genome equivalents, which was supported by hybridization results with homologous and heterologous probes.