Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Safety and feasibility of outpatient parenteral antimicrobial therapy for patients with spinal infection.

Outpatient parenteral antimicrobial therapy (OPAT) is a cost-effective method of administering intravenous antimicrobial therapy. Although OPAT is well established in the UK and US healthcare systems, few centres in Europe perform it. Here we analysed OPAT for the treatment of patients with spinal infections at our institution. In this retrospective study, patients with spinal infection who required intravenous (i.v.) antimicrobial treatment between 2018 and 2021 were analysed. The duration of short-term antimicrobial treatment for skin and soft tissue infections and complex infections requiring long-term antimicrobial treatment, such as spinal bone or joint infections, were analysed. All patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed. For this study a total of 52 patients who were treated via OPAT due to spinal infections were analyzed. In 35 cases (69.2%) complex spinal infection was reason for i.v. antimicrobial therapy. Surgery was required in 23 of these 35 patients (65.7%). The average hospital stay for these patients was 12 ± 6 days. The remaining 17 patients were treated for an infection of the soft tissue or the skin and hospital stay for these patients was on average 8 ± 4 days. Gram-positive organisms were isolated in 64.4%. Staphylococcus aureus followed by other Staphylococcus species, was the most common detected organism. After discharging i.v. antimicrobial treatment was given for an average of 20 ± 14 days. The duration of antimicrobial treatment for soft tissue was 10.8 ± 8 days, and for complex infections 25.1 ± 18 days. The mean follow-up was 21 ± 14 months. There was one case of readmission due to treatment failure. There were no difficulties encountered in implementing OPAT. OPAT is a feasible and effective option for delivering intravenous antimicrobial therapy to patients with spinal infections who can be managed without hospitalisation. OPAT offers patient-centred treatment at home while avoiding the risks associated with hospitalisation, with high levels of patient satisfaction.

Efficacy and safety of outpatient parenteral antibiotic therapy in patients with infective endocarditis: a meta-analysis.

OBJECTIVE: To investigate the clinical outcome of patients with infective endocarditis (IE) during and after outpatient parenteral antimicrobial treatment (OPAT), and to further clarify the safety and efficacy of OPAT for IE patients. METHODS: Through December 20, 2021, a total of 331 articles were preliminarily searched in Pubmed, Web of Science, Cochrane Library and Embase, and 9 articles were eventually included in this study. RESULTS: A total of 9 articles comprising 1,116 patients were included in this study. The overall mortality rate of patients treated with OPAT was 0.04 (95% CI, 0.02-0.07), that means 4 deaths per 100 patients treated with OPAT. Separately, mortality was low during the follow-up period after OPAT treatment, with an effect size (ES) of 0.03 (95%CI, 0.02-0.07) and the mortality of patients during OPAT treatment was 0.04 (95% CI, 0.01-0.12). In addition, the readmission rate was found to be 0.14 (95% CI, 0.09-0.22) during the follow-up and 0.18 (95% CI, 0.08-0.39) during treatment, and 0.16 (95% CI, 0.10-0.24) for patients treated with OPAT in general. Regarding the relapse of IE in patients, our results showed a low overall relapse rate, with an ES of 0.03 (95% CI, 0.01-0.05). In addition, we found that the incidence of adverse events was low, with an ES of 0.26 (95% CI, 0.19-0.33). CONCLUSIONS: In general, the incidence of adverse events and mortality, readmission, and relapse rates in IE patients treated with OPAT are low both during treatment and follow-up period after discharge, indicating that OPAT is safe and effective for IE patients. However, our study did not compare routine hospitalization as a control group, so conclusions should be drawn with caution. In order to obtain more scientific and rigorous conclusions and reduce clinical risks, it is still necessary to conduct more research in this field and improve the patient selection criteria for OPAT treatment, especially for IE patients. Finally, clinical monitoring and follow-up of OPAT-treated patients should be strengthened.

Understanding the relationship between patient characteristics and complication in veterans discharged on parenteral antibiotic therapy.

BACKGROUND: Many facilities utilize outpatient parenteral intravenous (IV) antimicrobial therapy (OPAT) to reduce cost, length of stay, and risk of nosocomial infections. OBJECTIVE: The objective of this study was to analyze patient demographics, substance use, mental and physical health diagnoses, and social determinants of health to seek relationships with complications for veterans discharged from the Zablocki Veterans Affairs Medical Center (ZVAMC) on OPAT. METHODS: This study was a retrospective chart review of veterans who completed OPAT between the years of 2013 and 2017 at the ZVAMC in Milwaukee, Wisconsin. Prior to discharge, patients were screened by the OPAT team for eligibility; patients were followed after discharge by pharmacy, home care, and providers. OPAT complication was defined as antibiotic change/dose adjustment, IV catheter complication, or an additional hospital visit secondary to current infection or therapy. RESULTS: 294 veterans' charts were reviewed. Of these patients, 106 (36.05%) had a complication. Tobacco use was the only factor significantly associated with OPAT complication. CONCLUSIONS: Cohabitation, employment status, mental health diagnosis and alcohol use were not associated with OPAT failure; however, tobacco use merits further review for use in OPAT screening protocols.

The Clinical Desire for Pressurized Intraperitoneal Aerosol Chemotherapy in South Korea: An Electronic Survey-based Study.

BACKGROUND/AIM: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea. PATIENTS AND METHODS: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions. RESULTS: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW). CONCLUSION: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC.

Intraperitoneal lidocaine instillation during abdominal hysterectomy: A systematic review and meta-analysis of randomized placebo-controlled trials.

AIM: To perform a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that inspected the analgesic benefits of intraperitoneal lidocaine instillation among patients undergoing abdominal hysterectomy. METHODS: Five electronic databases were inspected from till August 5, 2021. The eligible RCTs were evaluated for risk of bias. The pooled endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). RESULTS: Five RCTs met the inclusion criteria comprising 263 patients (119 and 117 patients were allocated to lidocaine and control group, respectively). The included RCTs demonstrated a low risk of bias. The postoperative pain score at rest was significantly lower in favor of the lidocaine group (MD=-1.01, 95% CI [-1.20, -0.81], p<0.001), and subgroup analysis demonstrated the same at 2, 4, 8, 12, 24, and 48 h postoperatively. Moreover, the postoperative pain score at moving was significantly lower in favor of the lidocaine group (MD=-0.67, 95% CI [-1.01, -0.33], p<0.001), and subgroup analysis demonstrated the same at 2 and 48 h postoperatively. The postoperative morphine consumption during 0-24 h was significantly lower in favor of the lidocaine group (n = 5 RCTs, MD=-7.29 mg, 95% CI [-13.22, -1.37], p = 0.02). The rate of postoperative vomiting was significantly lower in favor of the lidocaine group (n = 4 RCTs, RR=0.54, 95% CI [0.31, 0.95], p = 0.03). CONCLUSION: Among patients undergoing abdominal hysterectomy, intraperitoneal lidocaine instillation is feasible, cheap, safe, and associates with effective analgesia in terms of reduced postoperative pain score and morphine consumption.

Safety and efficacy of cell-free and concentrated ascites reinfusion therapy against cirrhotic ascites in comparison with malignancy-related ascites.

BACKGROUND AND AIM: Cell-free and concentrated ascites reinfusion therapy (CART) has been performed against cirrhotic ascites, one of the most common complications seen in patients with decompensated cirrhosis. The aim of this study is to investigate its safety and efficacy, and differences in clinical profiles from CART against malignancy-related ascites with different pathological background. METHODS: The present investigation involved a sub-analysis of data obtained from a prospective observational study of CART performed at 22 centers. The condition of each procedure, therapeutic options, laboratory data, performance status, dietary intake, and abdominal circumference of participants were analyzed. Clinical parameters were compared between before and after CART, with or without albumin infusion, and also primary diseases including cirrhosis and malignant disease. RESULTS: Between January 2014 and January 2015, a total of 48 and 275 CART procedures were performed in patients with cirrhosis and malignancies. In cirrhotic patients, serum albumin concentration increased significantly in groups both with and without concomitant albumin infusion (P = 0.002 and P = 0.023), and no significant difference in CART interval was seen between these groups (P = 0.393). CART interval was not significantly different between cirrhosis and malignancy groups (P = 0.334). Dietary intake significantly improved after CART in both groups (P = 0.043 and P < 0.001). Adverse events were with no clinical significance as observed in patients with malignancies. CONCLUSIONS: Cell-free and concentrated ascites reinfusion therapy was performed safely and effectively in patients with ascites related to decompensated cirrhosis and offers the potential efficacy to maintain plasma colloid osmotic pressure after paracentesis as well as in patients with malignancy.

Intervención con probióticos para la prevención de enterocolitis necrotizante en prematuros extremos menores de 1500 gramos o de 32 semanas / Probiotic intervention to prevent necrotizing enterocolitis in extremely preterm infants born before 32 weeks of gestation or with a birth weight of less than 1500 g

Introducción. Existe evidencia del beneficio de los probióticos en prevenir enterocolitis necrotizante en prematuros extremos. Desde 2015, se usa probiótico preventivo en el Servicio de Neonatología, Hospital Hernán Henríquez Aravena, Temuco, Chile.Objetivo. Evaluar el impacto de este probiótico en la incidencia, gravedad, necesidad de terapia quirúrgica y letalidad por enterocolitis necrotizante en prematuros extremos. Pacientes y método. Estudio retrospectivo de cohortes. Datos analizados con Stata. Se aplicó la prueba exacta de Fisher para comparar porcentajes y, para los promedios, la prueba t para varianzas distintas. Los egresados entre 2015 y 2017 recibieron Lactobacillus reuteri Protectis (LRP), dosis única (1 x 108 unidades formadora de colonias) desde los primeros días de vida hasta cumplir las 36 semanas de edad gestacional corregida. Los controles egresados entre 2012 y 2014 no recibieron LRP.Resultados. El 3,45 % de los casos tuvo algún grado de enterocolitis: grado i (el 64 %), ii (el 18 %), iii (el 18 %); requirió cirugía el 18 % y no hubo letalidad. El 3,75 % de los controles históricos presentaron enterocolitis: grado i (el 12 %), ii (el 35 %), iii (el 53 %); el 64,7 % requirió cirugía, y el 47 % falleció. El grupo intervenido presentó grado ii o iii en un 36 %; en el grupo control, la sumatoria de estos estadios fue del 88 %.Conclusión.LRP administrado en dosis única diaria al prematuro extremo no modificó la incidencia de enterocolitis, pero disminuyó su gravedad, la letalidad y necesidad de tratamiento quirúrgico.

Introduction. There is evidence of the beneficial effects of probiotics to prevent necrotizing enterocolitis in extremely preterm infants. Probiotic prevention has been used since 2015 in the Division of Neonatology of Hospital Hernán Henríquez Aravena, Temuco, Chile.Objective. To assess the impact of this probiotic on the incidence, severity, surgical treatment requirement, and fatality rate of necrotizing enterocolitis in extremely preterm infants.Patients and methods. Retrospective, cohort study. Data were analyzed using Stata. Fisher's exact test was used to compare percentages, and the unequal variances t-test, for averages. Infants discharged between 2015 and 2017 received Lactobacillus reuteri Protectis (LRP), in a single dose (1 x 108 colony forming units), since the first days of life until 36 weeks of corrected gestational age. Controls discharged between 2012 and 2014 did not receive LRP.Results. Some degree of enterocolitis was observed in 3.45 % of cases: stage I (64 %), stage II (18 %), stage III (18 %); 18 % required surgery, and there were no deaths. Among historical controls, 3.75 % had enterocolitis: stage I (12 %), stage II (35 %), stage III (53 %); 64.7 % required surgery, and 47 % died. In the intervention group, stage II or III accounted for 36 % of cases, whereas in the control group, for 88 %.Conclusion. Administering a single daily dose of LRP to extremely preterm infants did not affect the incidence of enterocolitis, but reduced its severity, fatality rate, and surgical treatment requiremen

Physiological effects of intraperitoneal versus subcutaneous insulin infusion in patients with diabetes mellitus type 1: A systematic review and meta-analysis.

The intraperitoneal route of administration accounts for less than 1% of insulin treatment regimes in patients with diabetes mellitus type 1 (DM1). Despite being used for decades, a systematic review of various physiological effects of this route of insulin administration is lacking. Thus, the aim of this systematic review was to identify the physiological effects of continuous intraperitoneal insulin infusion (CIPII) compared to those of continuous subcutaneous insulin infusion (CSII) in patients with DM1. Four databases (EMBASE, PubMed, Scopus and CENTRAL) were searched beginning from the inception date of each database to 10th of July 2020, using search terms related to intraperitoneal and subcutaneous insulin administration. Only studies comparing CIPII treatment (≥ 1 month) with CSII treatment were included. Primary outcomes were long-term glycaemic control (after ≥ 3 months of CIPII inferred from glycated haemoglobin (HbA1c) levels) and short-term (≥ 1 day for each intervention) measurements of insulin dynamics in the systematic circulation. Secondary outcomes included all reported parameters other than the primary outcomes. The search identified a total of 2242 records; 39 reports from 32 studies met the eligibility criteria. This meta-analysis focused on the most relevant clinical end points; the mean difference (MD) in HbA1c levels during CIPII was significantly lower than during CSII (MD = -6.7 mmol/mol, [95% CI: -10.3 --3.1]; in percentage: MD = -0.61%, [95% CI: -0.94 -- 0.28], p = 0.0002), whereas fasting blood glucose levels were similar (MD = 0.20 mmol/L, [95% CI: -0.34-0.74], p = 0.47; in mg/dL: MD = 3.6 mg/dL, [95% CI: -6.1-13.3], p = 0.47). The frequencies of severe hypo- and hyper-glycaemia were reduced. The fasting insulin levels were significantly lower during CIPII than during CSII (MD = 16.70 pmol/L, [95% CI: -23.62 --9.77], p < 0.0001). Compared to CSII treatment, CIPII treatment improved overall glucose control and reduced fasting insulin levels in patients with DM1.

The therapeutic effects of adipose-derived mesenchymal stem cells on obesity and its associated diseases in diet-induced obese mice.

Obesity is a global public health concern associated with increased risk of several comorbidities. Due to the limited effectiveness of current therapies, new treatment strategies are needed. Our aim was to examine the effect of adipose-derived mesenchymal stem cells (AD-MSCs) on obesity and its associated diseases in a diet-induced obese (DIO) animal model. C57BL6 mice were fed with either high fat diet (HFD) or CHOW diet for 15 weeks. Obese and lean mice were then subjected to two doses of AD-MSCs intraperitoneally. Mice body weight and composition; food intake; blood glucose levels; glycated hemoglobin (HbA1c), intraperitoneal glucose tolerance test and atherogenic index of plasma (AIP) were measured. Pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were also determined. AD-MSCs treatment reduced blood glucose levels, HbA1c and AIP as well as improved glucose tolerance in DIO mice. In addition, MSCs caused significant attenuation in the levels of inflammatory mediators in HFD-fed mice. Taken together, AD-MSCs were effective in treating obesity-associated diabetes in an animal model as well as protective against cardiovascular diseases as shown by AIP, which might be partly due to the attenuation of inflammatory mediators. Thus, AD-MSCs may offer a promising therapeutic potential in counteracting obesity-related diseases in patients.

Uso de la infusión intestinal continua de levodopa-carbidopa en pacientes con enfermedad de Parkinson avanzada en España. Subanálisis por comunidades autónomas / Continuous intestinal infusion of levodopa-carbidopa in patients with advanced Parkinson's disease in Spain: Subanalysis by autonomous community

OBJETIVOS: Comparar las características de los pacientes con enfermedad de Parkinson avanzada en tratamiento con infusión intestinal continua de levodopa-carbidopa (IICLC) y los datos de efectividad y seguridad de IICLC entre diferentes comunidades autónomas (CC. AA.). MÉTODOS: Estudio longitudinal observacional y retrospectivo. Se incluyeron 177 pacientes de 11 CC. AA. que iniciaron tratamiento con IICLC entre enero de 2006 y diciembre de 2011. Se compararon las características clínicas y demográficas, las variables de efectividad (cambios en el tiempo OFF, ON con y sin discinesias discapacitantes, cambios en la escala de Hoehn y Yahr y puntuación de la Unified Parkinson's Disease Rating Scale, síntomas no motores e Impresión Clínica Global) y seguridad (acontecimientos adversos), y la tasa de suspensión de IICLC. RESULTADOS: Se hallaron diferencias significativas entre las CC. AA. en diversas variables basales: duración de la enfermedad hasta el inicio de IICLC, tiempo OFF (34,9-59,7%) y ON (con o sin discinesias; 2,6-48,0%), Hoehn y Yahr en ON, Unified Parkinson's Disease Rating Scale-III en ON y OFF, presencia de ≥ 4 síntomas motores y dosis de IICLC. En el seguimiento (> 24 meses en 9 de 11 CC. AA.) hubo diferencias significativas en el porcentaje de tiempo OFF, tiempo ON sin discinesias discapacitantes, frecuencia de acontecimientos adversos e Impresión Clínica Global. La tasa de suspensión fue de entre 20-40% en todas las CC. AA., excepto en 2 (78 y 80%). CONCLUSIONES: Este estudio muestra una amplia variabilidad en la selección de los pacientes y en la efectividad y seguridad de IICLC entre las diferentes CC. AA. Podrían influir las características basales de los pacientes, la disponibilidad de un equipo multidisciplinar y la experiencia clínica

OBJECTIVES: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain. METHODS: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients' clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation. RESULTS: Significant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of ≥ 4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (> 24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2 CAs). CONCLUSIONS: This study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients' baseline characteristics, the availability of multidisciplinary teams, and clinical experience

Cost minimization analysis of outpatient parenteral/oral antibiotic therapy at a trauma hospital: Public health system.

OBJECTIVE: To evaluate the impact of outpatient parenteral antimicrobial therapy (OPAT) on a public hospital in a middle-income country. DESIGN: A retrospective, observational study analyzing the economic data retrieved on the dehospitalization of patients on antibiotic therapy. SETTING: Public university trauma hospital. PATIENTS: Data were collected from June 2017 to May 2020. Antibiotic cost, hospital length of stay, and risk of multidrug-resistant (MDR) infection or colonization were reviewed, along with the break-even point at which a balance occurs between OPAT antimicrobial costs and all in-hospital costs. A cumulative risk curve was constructed showing the incidence of MDR during the review period. RESULTS: In total, 225 patients were studied. The implementation of OPAT resulted in a reduction of $156,681 (49.6%), which is equivalent to an average of $696 per patient, as well as a shortened length of stay, from 33.5 to 15.7 days. OPAT reduces the risk of acquiring infection by MDR bacteria by having the final treatments administered outside of the hospital environment. The breakeven curves, comparing the duration of the OPAT to daily medication costs, allowed for the prediction of the time and dollar costs of antibiotic therapy. CONCLUSIONS: OPAT presented a significant cost savings, shortened length of stay, and reduced risk of contamination of patients by MDR.

¿Estamos sobredosificando el metamizol por vía parenteral? / Are we overdosing parenteral metamizole?

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Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases - The Hong Kong experience and literature review.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief. METHODS: This is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival. RESULTS: Between 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients - 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31). CONCLUSION: CRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients - improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit.

Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.

BACKGROUND: Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight infants. Dietary supplementation with probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity.  OBJECTIVES: To determine the effect of supplemental probiotics on the risk of NEC and mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 2) in the Cochrane Library; MEDLINE Ovid (1946 to 17 Feb 2020), Embase Ovid (1974 to 17 Feb 2020), Maternity & Infant Care Database Ovid (1971 to 17 Feb 2020), the Cumulative Index to Nursing and Allied Health Literature (1982 to 18 Feb 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing probiotic supplementation with placebo or no probiotics in very preterm or very low birth weight infants. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on NEC, all-cause mortality, late-onset infection, and severe neurodevelopmental impairment. MAIN RESULTS: We included 56 trials in which 10,812 infants participated. Most trials were small (median sample size 149). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were the main potential sources of bias in about half of the trials. Trials varied by the formulation of the probiotics. The most commonly used preparations contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., and Streptococcus spp. alone or in combinations. Meta-analysis showed that probiotics may reduce the risk of NEC: RR 0.54, 95% CI 0.45 to 0.65 (54 trials, 10,604 infants; I² = 17%); RD -0.03, 95% CI -0.04 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 25 to 50. Evidence was assessed as low certainty because of the limitations in trials design, and the presence of funnel plot asymmetry consistent with publication bias. Sensitivity meta-analysis of trials at low risk of bias showed a reduced risk of NEC: RR 0.70, 95% CI 0.55 to 0.89 (16 trials, 4597 infants; I² = 25%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100. Meta-analyses showed that probiotics probably reduce mortality (RR 0.76, 95% CI 0.65 to 0.89; (51 trials, 10,170 infants; I² = 0%); RD -0.02, 95% CI -0.02 to -0.01; NNTB 50, 95% CI 50 to 100), and late-onset invasive infection (RR 0.89, 95% CI 0.82 to 0.97; (47 trials, 9762 infants; I² = 19%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100). Evidence was assessed as moderate certainty for both these outcomes because of the limitations in trials design. Sensitivity meta-analyses of 16 trials (4597 infants) at low risk of bias did not show an effect on mortality or infection. Meta-analysis showed that probiotics may have little or no effect on severe neurodevelopmental impairment (RR 1.03, 95% CI 0.84 to 1.26 (five trials, 1518 infants; I² = 0%). The certainty on this evidence is low because of limitations in trials design and serious imprecision of effect estimate. Few data (from seven of the trials) were available for extremely preterm or extremely low birth weight infants. Meta-analyses did not show effects on NEC, death, or infection (low-certainty evidence). AUTHORS' CONCLUSIONS: Given the low to moderate level of certainty about the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or very low birth weight infants, and particularly for extremely preterm or extremely low birth weight infants, further, large, high-quality trials are needed to provide evidence of sufficient quality and applicability to inform policy and practice.

A phase I dose-escalation study of oxaliplatin delivered via a laparoscopic approach using pressurised intraperitoneal aerosol chemotherapy for advanced peritoneal metastases of gastrointestinal tract cancers.

OBJECTIVE: The objectives were to define the maximum tolerated dose (MTD), safety profile and pharmacokinetics (PKs) of intraperitoneal oxaliplatin delivered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal carcinomatosis from gastrointestinal tract cancers. METHODS: PIPAC was applied every 4-6 weeks, for 5 cycles, in a phase I dose-escalation study using a 3 + 3 design. The first dose level was 90 mg/m2 with planned increases of 50 mg/m2 per level. Platinum concentration was measured in plasma, tissues and intraperitoneal fluid samples. The trial was registered at ClinicalTrials.gov (NCT03294252). RESULTS: Ten patients with 33 PIPAC sessions were included. No dose limiting toxicity (DLT) occurred at 90 mg/m2 and two at 140 mg/m2. The MTD was therefore set at 90 mg/m2. Overall treatment included a median number of three PIPAC sessions (range: 1-5) and secondary complete cytoreductive surgery for two patients. Overall safety showed 67 grade I-II and 11 grade III-IV toxicities, usually haematologic, digestive (nausea/vomiting, abdominal pain), and fatigue. Oxaliplatin concentrations were three- to four-fold higher in tissue in contact with aerosol than in muscle without contact. At 140 mg/m2, the plasma oxaliplatin concentration was high with Cmax and area under the curve (AUC)0-48h of 1035 µg/l and 9028 µg h/L, respectively. CONCLUSIONS: The MTD of oxaliplatin during PIPAC is 90 mg/m2. PK data demonstrate a high tumour concentration and a significant systemic absorption.

Bacteriemia en pacientes con nutrición parenteral central: prevalencia, factores asociados y tratamiento / Catheter-related bloodstream infections in patients receiving central parenteral nutrition: prevalence, associated factors, and treatment

INTRODUCCIÓN: la infección relacionada con el catéter es una de las complicaciones del tratamiento con nutrición parenteral central (NPC) que generan una mayor morbimortalidad. OBJETIVOS: el objetivo principal fue analizar la prevalencia de la bacteriemia asociada al catéter en pacientes con nutrición parenteral central. Los objetivos secundarios fueron: a) evaluar si el tipo de catéter central, la duración de la nutrición parenteral central, el índice de masa corporal o la estancia en la unidad de cuidados intensivos son factores asociados al desarrollo de bacteriemia; b) analizar el manejo terapéutico de la infección. MATERIAL Y MÉTODOS: se trata de un estudio observacional retrospectivo. Se incluyeron los pacientes que recibieron nutrición parenteral central tras una intervención quirúrgica entre julio de 2018 y marzo de 2019. La asociación de las variables con el desarrollo de la bacteriemia se analizó mediante regresión logística. RESULTADOS: el 7,3 % (IC 95 %: 3,9-13,3) (n = 9/123) de los pacientes desarrollaron bacteriemia relacionada con el catéter. El único factor asociado al desarrollo de la infección fue la duración de la nutrición parenteral central (OR = 1,12; IC 95 %: 1,05-1,20; p = 0,001). CONCLUSIONES: la prevalencia de la bacteriemia relacionada con el catéter en este estudio es baja. La duración del tratamiento con nutrición parenteral central parece estar relacionada con el desarrollo de la bacteriemia. Sin embargo, se necesitan más estudios para identificar factores de riesgo que permitan minimizar este tipo de complicaciones

BACKGROUND: catheter-related infection is one of the complications of central parenteral nutrition treatment with the highest morbidity and mortality. OBJECTIVES: the primary endpoint of this study was to analyze the prevalence of bloodstream infection in patients with central parenteral nutrition. Secondary objectives included: a) an assessment of whether type of central catheter, duration of parenteral nutrition treatment, body mass index, or being admitted to the intensive care unit are factors associated with the development of bloodstream infection; b) an analysis of the therapeutic approach. MATERIAL AND METHODS: this was a retrospective observational study. All patients who received central parenteral nutrition after surgery between July 2018 and March 2019 were included. The association between the different variables and the development of bloodstream infection was analyzed by logistic regression. RESULTS: the prevalence of bloodstream infection was 7.3 % (95 % CI: 3.9-13.3) (n = 9/123 patients). The duration of central parenteral nutrition was the only variable associated with the development of bloodstream infection (OR = 1.12; 95 % CI:1.05-1.20; p = 0.001). CONCLUSIONS: the prevalence of catheter-related bloodstream infection in this study is low, and the duration of central parenteral nutrition seems to be related to its development. However, further studies are needed to identify risk factors that might help reduce this kind of complications

Inequitable access to an outpatient parenteral antimicrobial therapy service: linked cross-sectional study.

STUDY AIM: To assess whether Outpatient Parenteral Antimicrobial Therapy (OPAT) is provided equitably across gender and social groups in a tertiary care setting. BACKGROUND: OPAT is a widely used and growing approach in high income countries to early discharge or admission avoidance for patients requiring intravenous antimicrobials. There is however a risk that equitable access to healthcare could be eroded unintentionally by expansion of outpatient or ambulatory approaches such as this. Anecdotal evidence in our service, and from published studies, have identified a gender and social group equity gap in outpatient services. METHODS: Service data on inpatient cellulitis episodes over a seven-year period were matched to OPAT referral data to create a retrospective cross-sectional linked dataset. All individuals admitted from 2012 to 2017 inclusive for a primary diagnosis of cellulitis were included: 6295 admissions of 4944 individuals. Demographics, number of co-morbidities, length of hospital stay, number of admissions, distance from OPAT unit and Scottish Index of Multiple Deprivation (SIMD; as a metric of deprivation) were recorded. Adjusted odds of a referral to OPAT across SIMD quintiles and for females compared to males were calculated using multiple logistic regression. RESULTS: Inequitable access to OPAT was identified. Deprivation was negatively associated with likelihood of OPAT referral. Inpatients from the most affluent SIMD quintile were more than twice as likely to have received an OPAT referral compared to those resident in the most deprived quintile (adjusted OR 2.08, 95% CI: 1.60-2.71, p <  0.0001). Women were almost a third less likely to receive an OPAT referral than men (adjusted OR 0.69, 95% CI: 0.58 to 0.82, p <  0.001). Results were adjusted for age, number of co-morbidities, admissions, length of stay, distance from nearest OPAT unit, time since first admission, deprivation and gender. CONCLUSIONS: OPAT services and other ambulatory care programmes should routinely evaluate the equity of their service provision and consider how they can reduce any identified imbalance. It is a critical responsibility of service planning to ensure an inequitable system does not develop, with those least able to access ambulatory care dispossessed of the associated benefits.