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Changes in the organization of the clinical care wards, requested by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, have influenced the environmental circulation of other pathogens. The implementation of prevention procedures may have led to a decrease in the incidence of healthcare-associated infections. We aimed to investigate the impact of prevention and control measures for preventing the COVID-19 spread on the incidence of bacterial sepsis and invasive fungal infections in neonates and infants requiring major surgery. We compared the incidence of bacterial and fungal sepsis and their risk factors observed before the SARS-CoV-2 pandemic (from 01/10/2018 to 29/02/2020) with those observed during the pandemic (from 01/03/2020 to 07/05/2021) in 13 level III Neonatal Intensive Care Units in Italy, through a secondary analysis of data, collected during a prospective multicenter study (REF). The patients enrolled were infants within three months of life, hospitalized in the two periods in the participating centers to undergo major surgery. Among 541 enrolled patients, 324 (59.9%) were born in the pre-pandemic period and 217 (40.1%) during the pandemic. The incidence density (ID) of any infection in the pre-pandemic period was 16.0/1000 patient days versus 13.6/1000 patient days in the pandemic period (p < 0.001). One hundred and forty-five (145/324; 44.8%) patients developed at least one episode of bacterial sepsis in the pre-pandemic period, versus 103/217 (31.8%) patients, during the pandemic (p = 0.539). Concerning fungal sepsis, 12 (3.7%) patients had one episode in the pre-pandemic period versus 11 (5.1%) patients during the pandemic (p = 0.516). The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics pre-surgery, and that of proton pump inhibitors during the SARS-CoV-2 pandemic compared with the previous period., Conclusions: In our cohort of patients with major surgical needs, the reduction of CVC days, pre-surgery antibiotics administration, and current use of proton pump inhibitors, during the SARS-CoV-2 pandemic, led to a decrease in the incidence of late-onset sepsis., What Is Known: • Most cases of late-onset sepsis in neonates are referred to as central line-associated bloodstream infections. • In adults, the COVID-19 outbreak negatively influenced healthcare-associated infection rates and infection clusters within hospitals., What Is New: • In neonates and infants undergoing major surgery the incidence density of infections was lower in the pandemic period than before. • The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics before surgery, and that of proton pump inhibitors during the pandemic compared with previously., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Catheter-associated bloodstream infection, also known as CLABSI, is the most serious consequence of central venous access devices. These infections increase the risk of mortality and morbidity. The use of central line bundles in clinical settings is increasing worldwide with the purpose of lowering the risk of catheter-associated bloodstream infections. In this study, we investigated the effect of implementing a central line bundle for the prevention of CLABSIs, the distribution of pathogens, and the duration of time it took for CLABSIs to develop in patients who had subclavian-inserted central venous catheters. This research project was a cross-sectional study investigation carried out in a pediatric tertiary teaching hospital. Participants consisted of children who had been admitted to the pediatric critical care unit with subclavian catheters during a period of 13 years. We compared the prebundle period with the bundle period for CLABSI specifically focusing on the time to infection, the number of polymicrobial infections, the proportion of Candida parapsilosis, and the percentage of Coagulase-negative staphylococci (CoNS). The "prebundle period" included the period from May 2007 to May 2013, and the "bundle period" included the period from June 2013 to June 2020. Throughout the course of the study, a total of 286 cases of CLABSI were documented. Among these patients, 141 (49.3%) had CLABSIs associated with subclavian catheters. During the prebundle period, 55 CLABSIs were diagnosed in 5235 central line days, with an overall rate of 10.5 CLABSIs per 1000 central line days; after the implementation of central line bundle, 86 CLABSIs were diagnosed in 12,450 CL days, with an overall rate of 3.6 CLABSIs per 1000 CL days. This showed a statistically significantly lower rate in the bundle period (p = 0.0126). In the prebundle period, the mean time to develop CLABSI was 15 days, whereas during the bundle period, the mean time to develop CLABSI was 27.9 days, a significantly longer time to onset (p = 0.001). While the percentage of other microorganisms was not statistically different between the prebundle and bundle periods (p > 0.05), the percentage of C. parapsilosis was significantly higher in the prebundle period (p = 0.001).   Conclusion: The results of this study imply that the use of central line bundles not only reduces the incidence of CLABSI but also delays the time to which CLABSI patients acquire an infection. In addition, as a direct consequence of the CLB, the number of CLABSIs caused by gram-positive cocci did not increase, while the proportion of CLABSIs caused by C. parapsilosis decreased. What is Known: • The most significant negative consequence of central venous access devices is catheter-associated bloodstream infections. • "Care bundles" for CLABSI prevention have been reported to reduce the CLABSI rate. What is New: • Consider what would happen if the "Care bundle" failed to prevent CLABSI. • The findings of this study imply that using central line bundles not only reduces the risk of CLABSI but also extends the time it takes for patients to develop CLABSI. While the number of CLABSIs caused by gram-positive cocci did not increase as a direct result of CLB, the rate of CLABSIs caused by C. parapsilosis, which has recently become a major problem, has decreased., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sepsis due to the administered probiotic strain/s is a barrier against adoption of prophylactic probiotic supplementation in preterm infants to reduce the risk of necrotising enterocolitis (NEC ≥ Stage II), all-cause mortality, late-onset sepsis, and feeding intolerance. We aimed to conduct a systematic review for reports of probiotic sepsis in preterm infants (gestation < 37 weeks). Databases including PubMed, Embase, Emcare, Cochrane Central library, and Google Scholar were searched in August 2021 and updated in Jan 2022. Probiotic sepsis was defined as positive blood/CSF culture isolating administered probiotic strain with symptoms suggestive of infection. Data collection included birth weight, gestation, comorbidities (e.g. gut surgery, NEC), presence of central venous catheters, treatment, and outcome. Literature search revealed 1569 studies. A total of 16 reports [randomised control trial (RCT): none; non-RCT: 1; case series: 8; case report: 7] involving 32 preterm infants with probiotic sepsis were included after exclusions for various reasons. Majority of the cases were born < 32 weeks' gestation. Bifidobacterium (N = 19) was the most commonly isolated organism followed by Lactobacillus (N = 10), and Saccharomyces (N = 3). A total of 25/32 cases were confirmed to be due to the administered probiotic strain on full genomic analysis. Two studies reported one neonatal death each. Twelve neonates had comorbidities. Majority were treated with antibiotics (29/32) whereas others (3/32) required antifungal treatment., Conclusion: Probiotics sepsis is relatively an uncommon event in preterm infants. Majority of the cases recovered after antibiotic or antifungal treatment. The importance of optimal surveillance and treatment of probiotic sepsis and research towards alternatives to probiotics (e.g. postbiotics) is emphasised., What Is Known: • Probiotics have been shown to reduce necrotising enterocolitis, late-onset sepsis, all-cause mortality, and time to reach full enteral feeds in preterm infants. • Despite the evidence, use of probiotics is not universal due to concerns regarding probiotic-associated sepsis in preterm infants., What Is New: • This comprehensive systematic review showed that probiotic sepsis is a relatively rare phenomenon in preterm infants. • All except one case where the diagnosis was uncertain recovered after antimicrobial therapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants' clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetes and sepsis are important causes of morbidity and mortality worldwide, and diabetic patients represent the largest population experiencing post-sepsis complications and rising mortality. Dysregulated immune pathways commonly found in both sepsis and diabetes contribute to worsen the host response in diabetic patients with sepsis. The impact of diabetes on mortality from sepsis is still controversial. Whereas a substantial proportion of severe infections can be attributed to poor glycemic control, treatment with insulin, metformin and thiazolidinediones may be associated with lower incidence and mortality for sepsis. It has been suggested that chronic exposure to high glucose might enhance immune adaptation, leading to reduced mortality rate in septic diabetic patients. On the other hand, higher risk of acute kidney injury has been extensively documented and a suggested lower risk of acute respiratory distress syndrome has been recently questioned. Additional investigations are ongoing to confirm the protective role of some anti-diabetic treatments, the occurrence of acute organ dysfunction, and the risk/benefit of less stringent glycemic control in diabetic patients experiencing sepsis. Based on a MEDLINE/PubMed search from inception to December 31, 2020, the aim of this review is therefore to summarize the strengths and weaknesses of current knowledge on the interplay between diabetes and sepsis., (© 2021. The Author(s).)

Aim: The purpose of this study was to clarify the medium to long term survival of aseptic revision total knee arthroplasty (RTKAs) and identify the common modes of failure following RTKAs., Materials and Methods: A multi-center, retrospective study included all aseptic RTKAs performed at three tertiary referral hospitals between 2003 and 2016. Patients were excluded if the revision was for prosthetic joint infection (PJI) or they had previously undergone revision surgery. Minor revisions not involving the tibial or femoral components were also excluded. Demographics, surgical data and post-operative outcomes were recorded and analyzed. Survival analysis was performed and the reasons for revision failure identified., Results: Of 235 aseptic RTKAs identified, 14.8% underwent re-revision at mean follow-up of 8.3 years. Survivorship of RTKA was 93% at 2 years and 83% at 8 years. Average age at revision was 72.9 years (range 53-91.5). The most common reasons for failure following RTKA were periprosthetic joint infection (PJI) (40%), periprosthetic fracture (25.7%) and aseptic loosening (14.3%). Of those whose RTKA failed, the average survival was 3.33 years (8 days-11.4 years). No demographic or surgical factors were found to influence RTKA survival on univariate or multivariate analysis., Conclusion: PJI and periprosthetic fracture are the leading causes of re-revision surgery following aseptic revision TKA. Efforts to improve outcomes of aseptic revision TKA should focus on these areas, particularly prevention of PJI., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Studies in preterm infants have shown an association between late-onset sepsis (LOS) and the development of bronchopulmonary dysplasia (BPD). It is unknown whether clinical or biochemical characteristics during sepsis modulate the risk for BPD. This single-center retrospective cohort study included all patients with a gestational age < 30 weeks, born between 2009 and 2015, in whom empiric antimicrobial treatment was initiated > 72 h after birth and continued for at least 5 days, independent on microbiological results. The association between clinical and biochemical characteristics of LOS and the development of BPD in survivors were assessed with multivariate logistic regression analysis adjusted for early-onset sepsis, small for gestational age, and gestational age. Of the 756 admitted infants, 256 infants (mean GA: 27.0 weeks; birthweight: 924 grams) had at least one LOS episode, of whom 79 (30.9%) developed BPD. Analyses showed that only the need for and duration of mechanical ventilation during LOS were independently associated with an increased risk for BPD (adjusted OR 2.62, 95% CI 1.38, 4.96, p value 0.003, and OR 1.004, 95% CI 1.00, 1.007, p value 0.045, respectively).Conclusion: During a LOS, the need for and duration of mechanical ventilation are independently associated with the risk of developing BPD in preterm infants. What is Known: • Premature infants diagnosed with a late-onset sepsis are at higher risk of developing bronchopulmonary dysplasia • This association is mainly shown in infants with a positive blood culture What is New: • This study investigates the clinical and biochemical characteristics of late-onset sepsis and the development of bronchopulmonary dysplasia • The need for mechanical ventilation and duration of mechanical ventilation during late-onset sepsis are associated with an increased risk of developing bronchopulmonary dysplasia.

Purpose: To compare pregnancy outcomes in women with pPROM and a cervical cerclage in whom the cerclage was removed within 24 h and those in whom the cerclage was retained in situ., Methods: A two-center retrospective cohort study of women with a singleton gestation with pPROM at < 34 0/7  weeks of gestation in the presence of cervical cerclage (January 1, 2012-July 30, 2016). Maternal and perinatal outcomes were compared between women in whom cerclage was removed within 24 h from pPROM and those in whom cerclage was retained until the onset of delivery. The primary outcome was time from pPROM to delivery., Results: Seventy women met inclusion criteria. Cerclage was left in situ in 47 (67.1%) and removed in 23 (32.9%) women. Women in the cerclage retention group had a higher pPROM-to-delivery interval (7.0 ± 7.2 vs. 6.0 ± 10.9 days, p = 0.03), and were more likely to have a latency period > 48 h (87.2% vs. 65.2%, p = 0.03; aOR 3.9, 95% CI 3.1-4.9) or > 7 days (29.8% vs. 8.7%, p = 0.04; aOR 7.0, 95% CI 2.5-19.6) compared with women in whom cerclage was removed. Furthermore, chorioamnionitis rate was lower in the cerclage retention group compared to cerclage removal group (aOR 0.7, 95% CI 0.5-1.0). There were no differences between the groups in early neonatal sepsis, severe brain injury, or composite neonatal outcome., Conclusion: In women with pPROM and cervical cerclage, retention of cerclage may be associated with a longer latency period, and a lower chorioamnionitis rate, without an associated increase in the risk of neonatal infectious morbidity. Presentation information: The abstract of this study was presented as a poster at the 38th SMFM (Society of Maternal and Fetal Medicine) annual meeting, February 2018, Dallas, Texas, USA.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed., Methods: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations., Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy., Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

Chronic graft-versus-host disease (cGvHD) remains the most relevant factor affecting survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). Besides corticosteroids (and ibrutinib in the USA), there is no established therapy for cGvHD. Tocilizumab, a humanized IgG1 IL6-receptor antibody, has shown efficacy in acute GvHD and cGvHD. We retrospectively analyzed the efficacy and safety of tocilizumab for the treatment of advanced cGvHD. Eleven patients with severe steroid refractory cGvHD (median age 49; range 21-62 years) that received at least two prior lines of therapy for cGvHD (range 2-8 regimens) were treated with tocilizumab (q4w, dosage 8 mg/kg IV) with a median number of 15 cycles (range 2-31). NIH consensus criteria grading for cGvHD were recorded prior to tocilizumab administration and after 3, 6, and 12 months of therapy. All patients received additional concomitant immunosuppression (IS) but no new IS within the last 4 weeks before start of tocilizumab and response assessment was terminated before start of any new IS. The median number of days between alloHSCT and initiation of tocilizumab therapy was 1033 days. Organs involved at initiation of tocilizumab therapy were skin (100%, all grade 3), eyes (82%), fascia (82%), mouth (64%), lungs (55%), and genitals (18%). Overall, 7/10 patients (70%) showed partial remission, 2/10 patients (20%) showed progressive cGvHD, 1/10 patient (10%) showed mixed response, and 1 patient died due to sepsis before first response assessment 1.5 months after initiation of treatment. Four patients required subsequent new immunosuppressive treatment. Two patients developed bacterial sepsis, one of whom died. The overall survival and relapse-free survival were 82% with an average follow-up of 22 months (range 1.5-52 months). Tocilizumab seems a promising treatment option in advanced cGvHD but further evaluation within a phase II trial is required.

Purpose: This study aimed to examine the association between the use of intravenous contrast and non-recovery from dialysis-requiring acute kidney injury (AKI-D) and in-hospital mortality among patients with sepsis., Methods: This was a retrospective observational study using the Japanese Diagnosis Procedure Combination inpatient database between January 2011 and December 2016. We identified patients with septic AKI who began continuous renal replacement therapy (RRT) within 2-days of admission and underwent computed tomography. We compared patients with AKI-D with and without the use of intravenous contrast for computed tomography and performed propensity score matching to adjust for confounders for the association between exposure to intravenous contrast and outcomes, including a composite outcome of in-hospital mortality and RRT dependence at discharge and RRT duration., Results: From 3782 and 6619 patients with septic AKI-D with and without intravenous contrast exposure, respectively, 3485 propensity score-matched pairs were generated. No significant differences were found in the outcomes between the propensity score-matched groups: a composite outcome of in-hospital mortality and RRT dependence, 49.6% vs. 50.2% (odds ratio (OR) 0.98; 95% CI (confidence interval) 0.88, 1.07); in-hospital mortality, 45.3% vs. 46.1% (OR 0.97; 95% CI 0.87, 1.06); RRT dependence, 4.4% vs 4.1% (OR 1.08; 95% CI 0.85, 1.31); and median (interquartile range) of RRT duration, 4 [2-11] days vs. 4 [2-11] days (P = 0.58)., Conclusions: This large observational study did not support an association between intravenous contrast media and adverse in-hospital outcomes in patients with septic AKI-D. Further studies are warranted to assess the generalizability.

Purpose: Uterine angioleiomyoma is a rare type of leiomyoma variant and there are few cases reported in the literature. The definitive diagnosis is usually obtained only after the histopathologic examination because there are no specific imaging criteria for this disease. The objective of this article is to review published cases about this clinical condition., Methods: We report a case of giant angioleiomyoma superinfected by S. agalactiae with the development of latero-cervical distant metastasis in a premenopausal woman. Firstly, the case herein reported was orientated as an endometrial stroma sarcoma in the peri-operative histologic examination by frozen sections. It was treated with laparotomic total hysterectomy, bilateral salpingo-oophorectomy, inframesocolic omentectomy and pelvic and paraaortic lymph node dissection. Postoperative definitive anatomopathological analyses using a proper immunohistochemical panel revealed a case of uterine angioleiomyoma. We also review other case reports published about this clinical condition., Results: We present the first case reported in the literature, in our knowledge, of a giant angioleiomyoma superinfected by S. agalactiae with the development of distant septic metastases. Immunohistochemistry permitted the definitive diagnosis of angioleiomyoma. Treatments previously reported are hysterectomy or tumor resection and any patient recurred., Conclusions: The definitive diagnosis is usually obtained after the definitive histopathologic examination since the use of immunohistochemical study has an important role in this regard. Complete surgical removal of the lesion is the treatment of choice, with no recurrent cases reported to date.

Patients with dermatomyositis have multiple risk factors for serious and opportunistic infections, including immune dysregulation, long-term systemic corticosteroid treatment and comorbid health conditions. We sought to determine whether dermatomyositis is associated with increased odds and burden of systemic, opportunistic and antibiotic-resistant infections. We analyzed data from the Nationwide Inpatient Sample from 2002 to 2012, containing a cross-sectional representative 20% sample of all hospitalizations in the US. Overall, dermatomyositis was associated with serious infections in adults (multivariable logistic regression; adjusted odds ratio [95% confidence interval]: 2.19 [2.08-2.30]) and children (1.45 [1.20-1.76]). In particular, dermatomyositis was significantly associated with 32 of 48 and 15 of 48 infections examined in adults and children, respectively, including infections of skin, bone, joints, brain, heart, lungs, and gastrointestinal system, as well sepsis, antibiotic-resistant and opportunistic infections. Predictors of infections included non-white race/ethnicity, insurance status, history of long-term systemic corticosteroid usage, Cushing's syndrome (likely secondary to corticosteroid usage), diabetes, and cancer. Serious infections were associated with significantly increased inpatient cost and death in dermatomyositis patients. In conclusion, dermatomyositis is associated with higher odds, costs and inpatient mortality from serious and opportunistic infections.

Purpose: It has been acknowledged that implant wear correlates with the risk for periprosthetic osteolysis, being aggressive granulomatosis the worst expression of bone resorption. We sought to determine the clinical, radiological, and histological features of aggressive granulomatosis after primary total hip arthroplasty (THA)., Methods: We included nine cases with aggressive granulomatosis of the hip around cemented stems. Indications for revision THA consisted of progressive signs of extensive bone resorption or implant loosening. Mean follow-up since revision THA was 143 months (SD ± 59.4). We analysed clinical outcomes, component loosening and gross as well as histological characteristics of the granulomatous lesions., Results: Overall mean time between primary THA and revision surgery was 81 months (SD ± 20.8). All of the cases evidenced multiple ovoid tumour-like lesions around the stem with extensive bone loss. Only one case reported thigh pain before revision surgery, with radiological evidence of stem loosening; the remaining cases were asymptomatic with well-fixed implants. Gross anatomy findings revealed metallosis in the femoral canal and inside the cystic lesions. Pathology analysis showed monocyte-macrophage-dominated adverse foreign-body-type tissue reaction with fibroblastic reactive zones and granulomatous inflammation., Conclusions: We found a prevalence of 1% of this aseptic mode of implant failure. Since most of the retrieved stems were not loose, we did not find any alarming clinical symptoms anticipating implant failure. In this scenario, surgeons should be aware of the rapidly progressive nature of this entity and propose a revision THA in a timely fashion.

Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia for malignancies requiring urgent treatment. Thus, awareness of the presenting characteristics and prompt management is most important. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. However, optimal management may differ between neutropenic and non-neutropenic patients. The aim of the current guideline is to give evidence-based recommendations for hematologists, oncologists, and intensive care physicians on how to manage adult patients with neutropenia and sepsis.

Levosimendan and milrinone may be used in place of dobutamine to increase cardiac output in septic patients with a low cardiac output due to impaired cardiac function. The effects of the two inotropic agents on cardiac inflammation and left ventricular (LV) performance were examined in mice with cecal ligation and puncture (CLP)-induced sepsis. CLP mice displayed significant cardiac inflammation, as indicated by highly increased pro-inflammatory cytokines and neutrophil infiltration in myocardial tissues. When continuously given, levosimendan prevented but milrinone exaggerated cardiac inflammation, but they significantly reduced the elevations in plasma cardiac troponin-I and heart-type fatty acid-binding protein, clinical markers of cardiac injury. Echocardiographic assessment of cardiac function showed that the effect of levosimendan, given by an intravenous bolus injection, on LV performance was impaired in CLP mice, whereas milrinone produced inotropic responses equally in sham-operated and CLP mice. A lesser effect of levosimendan on LV performance after CLP was also found in spontaneously beating Langendorff-perfused hearts. In ventricular myocytes isolated from control and CLP mice, levosimendan, but not milrinone, caused a large increase in the L-type calcium current. This study represents that levosimendan and milrinone have cardioprotective properties but provide different advantages and drawbacks to cardiac inflammation/dysfunction in sepsis.

Urinary tract infection (UTI) is a common cause of sepsis in infants. Premature infants hospitalized at a neonatal intensive care unit often have risk factors for infection. In this group, the risk of UTI is not clearly known, and guidelines for urine analysis are not unanimous. We aimed to identify the risk of UTI in premature infants with central lines, suspected of late-onset sepsis. We analyzed all 1402 infants admitted to our hospital between 2006 and 2014 with a gestational age less than 32 weeks. Six hundred sixty-two episodes of sepsis evaluations were found with an unknown source of infection based on clinical symptoms. In half of this group, urine analysis was performed identifying UTI in 11.3% (24/212). In 13 of these infants (54%) with a UTI, infection was due to Candida albicans. In at least four episodes, the diagnosis and treatment would have been delayed if urine analysis had not been performed., Conclusion: Based on these findings, we conclude that in premature infants with central lines, urine analysis should be performed routinely when signs of infection occur beyond 72 h after birth. Urine collection should not be delayed and cultures should preferably be performed before the start of the antibiotic treatment. What is known: • In preterm infants, the presence of other risk factors for infection might make clinicians reluctant to obtain urine cultures during sepsis evaluation. • An internal survey demonstrated that there is no consensus within the NICUs in The Netherlands regarding urine analysis as part of LOS work-up. What is new: • The risk of UTI in the NICU population (11.3%) is comparable to term infants; therefore, urine analysis should be performed routinely when LOS is suspected. • Candida albicans was the most frequently (54%) detected pathogen causing UTI in this population.

Purpose: Maternal sepsis remains one of the leading causes of direct and indirect maternal mortality both in high- and low-income environments. In the last two decades, systems biology approaches, based on '-omics' technologies, have started revolutionizing the diagnosis and management of the septic syndrome. The scope of this narrative review is to present an overview of the basic '-omics' technologies, exemplified by cases relevant to maternal sepsis., Methods: Narrative review of the new '-omics' technologies based on a detailed review of the literature., Results: After presenting the main 'omics' technologies, we discuss their limitations and the need for integrated approaches that encompass research efforts across multiple '-omics' layers in the '-omics' cascade between the genome and the phenome., Conclusions: Systems biology approaches are revolutionizing the research landscape in maternal sepsis. There is a need for increased awareness, from the side of health practitioners, as a requirement for the effective implementation of the new technologies in the research and clinical practice in maternal sepsis.

Over the coming years, accelerating progress against cancer will be associated with an increased number of patients who require life-sustaining therapies for infectious or toxic chemotherapy-related events. Major changes include increased number of cancer patients admitted to the ICU with full-code status or for time-limited trials, increased survival and quality of life in ICU survivors, changing prognostic factors, early ICU admission for optimal monitoring, and use of noninvasive diagnostic and therapeutic strategies. In this review, experts in the management of critically ill cancer patients highlight recent changes in the use and the results of intensive care in patients with malignancies. They seek to put forward a standard of care for the management of these patients and highlight important updates that are required to care for them. The research agenda they suggest includes important studies to be conducted in the next few years to increase our understanding of organ dysfunction in this population and to improve our ability to appropriately use life-saving therapies or select new therapeutic approaches that are likely to improve outcomes. This review aims to provide more guidance for the daily management of patients with cancer, in whom outcomes are constantly improving, as is our global ability to fight against what is becoming the leading cause of mortality in industrialized and non-industrialized countries.

Background: Sepsis is a major reason for intensive care unit (ICU) admission, also in resource-poor settings. ICUs in low- and middle-income countries (LMICs) face many challenges that could affect patient outcome., Aim: To describe differences between resource-poor and resource-rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU., Findings: Although many bacterial pathogens causing sepsis in LMICs are similar to those in high-income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources., Conclusions: Addressing both disease-specific and setting-specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost-effective in LMIC setting, more detailed evaluation at both at a macro- and micro-economy level is necessary. Sepsis management in resource-limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.

The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2 % and 94.9 ± 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP.

Management of intractable haematuria and obstructive urosepsis from upper tract urothelial carcinoma can be problematic in patients not suitable for surgery, chemotherapy or radiotherapy. Interventional radiology techniques provide alternative approaches in this setting, such as complete kidney embolization to cease urine output, percutaneous nephrostomy, antegrade injection of sclerotherapy agents and sterilisation of the upper collecting system. Related approaches have been successfully employed to sclerose renal cysts, lymphoceles, chyluria and intractable lower tract haemorrhage. No reports of percutaneous, antegrade sclerotherapy in the upper urinary tract have previously been published. We present a case of recurrent haematuria and obstructive urosepsis caused by invasive upper tract urothelial carcinoma in a non-operative patient, which was treated with renal embolisation and percutaneous upper tract urothelial sclerotherapy.

Secondary diffuse peritonitis still has a high morbidity and mortality even now; therefore, the various strategies and options for the different surgical therapies are undergoing an evidence-based review. Laparoscopic lavage without resection of the focus of sepsis for example is a profoundly different approach in the treatment of diffuse peritonitis from the damage control-based strategy of surgery with initial laparostomy and deferred anastomosis. The evidential data for minimally invasive therapy are comparatively well-reviewed for appendicitis, cholecystitis and ulcerated perforation of the stomach and duodenum. In contrast, the evidence for laparoscopy and minimally invasive surgery with lavage and deferred anastomosis or damage control in secondary peritonitis has improved but is still low and cannot yet be clearly recommended. This article presents an overview of the currently available therapeutic methods for diffuse peritonitis and a critical consideration of the evidence-based data. The key recommendation is that the decision to use a surgical procedure based on the currently available data depends more on the severity of the abdominal sepsis, the duration, the age of the patient and comorbidities than on the individual technique.

Background: Secondary peritonitis remains associated with high mortality and morbidity rates. Treatment of secondary peritonitis is still challenging even in the era of modern medicine. Surgical intervention for source control remains the cornerstone of treatment besides adequate antimicrobial therapy and when necessary intensive medical care measures and resuscitation. A randomized clinical trial showed that relaparotomy on demand (ROD) after initial emergency surgery was the preferred treatment strategy, irrespective of the severity and extent of peritonitis., Results and Discussion: The effective and safe use of ROD requires intensive monitoring of the patient in a setting where diagnostic tests and decision making about relaparotomy are guaranteed round the clock. The lack of knowledge on timely and adequate patient selection, together with the lack of use of easy but reliable monitoring tools seem to hamper full implementation of ROD. The accuracy of the relaparotomy decision tool is reasonable for prediction of the formation of peritonitis and necessary selection of patients for computed tomography (CT). The value of CT in the early postoperative phase is unclear. Future research and innovative technologies should focus on the additive value of CT after surgical treatment for secondary peritonitis and on the further optimization of bedside prediction tools to enhance adequate patient selection for interventions in a multidisciplinary setting.

Background: The development of antibiotic-impregnated polymethyl methacrylate (PMMA) spacers is based on clinical experience and the use of antibiotic-loaded PMMA beads in septic bone surgery as well as antibiotic-loaded bone cement in arthroplasty beginning in the 1970s., Material and Methods: In the meantime hand-formed and prefabricated spacers are implanted in cases of sepsis to achieve high local antibiotic concentrations and bactericidal effects to eradicate the infection. Preformed spacers with gentamicin are commercially available and furthermore, clindamycin-loaded PMMA bone cement can also be used. In principle, all thermostable antibiotics can be mixed with PMMA cement., Significance: Spacers permit bridging of bone defects originating from trauma or septic bone segment resection. After joint resection spacers allow a certain degree of articulation and inhibit shortening of the extremity which has a positive effect on the soft tissue covering and its perfusion., Conclusion: The functional outcome after secondary arthroplasty is better if a spacer has been implanted compared to long-term immobilization without spacers. Nevertheless, spacers can also cause serious complications, such as dislocations and fractures. Antibiotic-loaded spacers have therefore widened the therapeutic options in sepsis surgery.

Unlabelled: Vitamin D has been linked with immunity, and the immunomodulatory role of this molecule in regulating key elements of the immune system has become an area of intense scientific investigation. We designed a case-control study to investigate whether neonates with early-onset neonatal sepsis (EONS) had lower levels of vitamin D. The primary exposure for the analysis in the study was the cord-blood level of 25-hydroxyvitamin D (25(OH)D). Of the 2571 live births occurring during the 18-month study period, 53 infants were admitted to the neonatal intensive care unit with suspected EONS. After clinical and laboratory confirmation, 40 newborns with EONS and 43 controls were analyzed. Cord-blood 25(OH)D levels of infants in the study group were significantly lower than that of the control group (median 12.6 ng/mL (3.1-78.9) vs. 21 (5-118); p = 0.038, respectively). In multivariate models, a low cord-blood 25(OH)D level (<30 ng/ml) was associated with an increased risk of EONS (OR = 5.6; 95% CI = 1.3-23.5)., Conclusion: Cord-blood 25(OH)D levels of neonates with EONS were significantly lower than that of the healthy controls, and a low level of cord-blood vitamin D was found to be associated with an increased risk of EONS. Further studies are warranted to confirm this association.

The human leukocyte antigen DR surface expression on CD14+ monocytes reflects the degree to which these cells have been activated. Given the central role monocytes and macrophages play in the immune system, a decreased human leukocyte antigen DR expression on CD14+ monocytes results in a hallmark of altered immune status during systemic inflammatory response syndrome. We hypothesize that human leukocyte antigen DR expression might be similarly altered after hematopoietic stem cell transplantation and during post-transplant complications. Using flow cytometry, this study investigates the human leukocyte antigen DR surface expression of CD14+ monocytes in 30 pediatric and young adult patients up to 1 year after hematopoietic stem cell transplantation. Normal values were derived from a control group of healthy children, adolescents, and young adults. Human leukocyte antigen DR expression decreased significantly prior and during bacterial infection or sepsis. By contrast, human leukocyte antigen DR expression levels were elevated before and at the time of viremia. Human leukocyte antigen DR expression was also elevated during acute graft-versus-host disease. In contrast, the expression was reduced when patients had hepatic veno-occlusive disease. A significant decrease of human leukocyte antigen DR expression was associated with a relapse of the underlying disease and before death. Human leukocyte antigen DR expression on CD14+ monocytes appears to be a promising parameter that might allow identification of patients at risk after hematopoietic stem cell transplantation.

Acute mesenteric ischemia is commonly seen in old patients. This study was undertaken to show that mesenteric ischemia might be seen in individuals under 40 years of age and that its diagnosis is challenging. Twenty-six patients with acute mesenteric ischemia under the age of 40 were studied. The main symptom on admission was abdominal pain. Symptom duration varied between 12 h and 5 days. The medical history of the patients revealed that 9 had no previous diseases. Other 17 had predisposing factors in the first evaluation. None of the patients had any history of narcotic or drug abuse. Ten patients presented with signs and symptoms of sepsis and septic shock. Preoperative diagnosis was acute intestinal ischemia only in 6 patients. Preoperatively, all the patients had intestinal or colonic ischemia and necrosis; one had additional ischemia of the liver, stomach, duodenum, and pancreas. Six patients had massive intestinal necrosis. The overall postoperative complication and overall mortality rates were 61.5 and 26.9 %, respectively. Complications and mortality were determined to be associated with previous pulmonary disease, acidosis, presence of septic shock, acute renal failure, extent of the ischemia and extent of resection, second look operations, previous cardiac events, and the kind of affected bowel (colon involvement).

Purpose: To assess the incidence, background, outcome and risk factors for death of severe sepsis in Japanese paediatric intensive care units (PICUs)., Methods: A data analysis of a prospective, multicentre, 3-year case registry from nine medical-surgical Japanese PICUs. Children with severe sepsis, aged 0-15 years, who were consecutively admitted to the participating PICUs from 1 January 2007 to 31 December 2009 were enrolled. The incidence, background, causative pathogens or infective foci, outcome and risk factors for death caused by severe sepsis were analysed., Results: One hundred forty-one cases were registered. After the exclusion of 14 patients because of incomplete data or inappropriate entry, 127 patients were eligible for the analysis. There were 60 boys and 67 girls, aged 23 [5-68] (median [IQR]) months and weighed 10 [5.5-16.5] kg. The incidence was 1.4 % of total PICU admissions. Sepsis was community-acquired in 35 %, PICU-acquired in 37 % and acquired in hospital general wards in 28 %. Methicillin-resistant Staphylococcus aureus was the most frequent pathogen. The crude 28-day mortality was 18.9 %, comparable to the mean PIM-2 predicted mortality (17.7 %). The mortality rate in patients with shock was significantly increased to 28 % compared to those without shock (5 %). The presences of existing haematological disorders (OR 8.97, 95 % CI, 1.56-51.60) and shock (OR 5.35, 1.04-27.44) were significant factors associated with mortality by multivariate analysis., Conclusions: The mortality from severe sepsis/septic shock in Japanese PICUs was ~19 %. Haematological disorders and presence of shock were associated with death.

Purpose: To measure renal adenosine triphosphate (ATP) (bioenergetics) during hypotensive sepsis with or without angiotensin II (Ang II) infusion., Methods: In anaesthetised sheep implanted with a renal artery flow probe and a magnetic resonance coil around one kidney, we induced hypotensive sepsis with intravenous Escherichia coli injection. We measured mean arterial pressure (MAP), heart rate, renal blood flow RBF and renal ATP levels using magnetic resonance spectroscopy. After 2 h of sepsis, we randomly assigned sheep to receive an infusion of Ang II or vehicle intravenously and studied the effect of treatment on the same variables., Results: After E. coli administration, the experimental animals developed hypotensive sepsis (MAP from 92 ± 9 at baseline to 58 ± 4 mmHg at 4 h). Initially, RBF increased, then, after 4 h, it decreased below control levels (from 175 ± 28 at baseline to 138 ± 27 mL/min). Despite decreased RBF and hypotension, renal ATP was unchanged (total ATP to inorganic phosphate ratio from 0.69 ± 0.02 to 0.70 ± 0.02). Ang II infusion restored MAP but caused significant renal vasoconstriction. However, it induced no changes in renal ATP (total ATP to inorganic phosphate ratio from 0.79 ± 0.03 to 0.80 ± 0.02)., Conclusions: During early hypotensive experimental gram-negative sepsis, there was no evidence of renal bioenergetic failure despite decreased RBF. In this setting, the addition of a powerful renal vasoconstrictor does not lead to deterioration in renal bioenergetics.

Purpose: To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency., Methods: A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed., Results: Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis)., Conclusions: Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis.

Purpose: More than a disorder of macrocirculation, sepsis is a disease affecting the microcirculation and the tissue metabolism. In vivo microdialysis (MD) is a bedside technique that can monitor tissue metabolic changes. We conducted this study aiming (1) to assess whether patients at different sepsis stages present with different MD-assessed tissue metabolic profiles and (2) to determine if different underlying types of infections and implicated pathogens are associated with dissimilar metabolic alterations., Methods: We studied 90 mechanically ventilated patients, 65 with septic shock and 25 with severe sepsis. An MD catheter was inserted in the subcutaneous adipose tissue of the upper thigh and interstitial fluid samples were collected along with arterial blood samples every 4 h for a maximum of 6 days. Lactate, pyruvate, glycerol, and glucose concentrations were measured., Results: During the study period, patients with septic shock had higher MD-assessed glycerol (P = 0.009), glycerol gradient (P = 0.016), and glucose (P = 0.004) than patients with severe sepsis, whereas tissue lactate, lactate gradient, and pyruvate dropped significantly with time (P = 0.007, <0.001, and <0.001, respectively) in both patient groups without any observed between-group difference. In addition, there was no between-group difference in their tissue lactate/pyruvate ratio on any day, nor did the ratio decrease significantly with time. Compared with pneumonia patients, and despite similar baseline clinical characteristics, those suffering from intra-abdominal infections showed a pattern of higher and progressively increasing tissue levels of glucose (P = 0.001) and glycerol (P = 0.001). Finally, patients harboring gram-positive infections had higher tissue levels of glycerol (P = 0.027) and glycerol gradient (P = 0.029) than patients with gram-negative infections., Conclusions: MD can detect tissue metabolic abnormalities that differ in relation to the sepsis stage and the type of underlying infection or responsible pathogen. Some of the MD-assessed abnormalities are not reflected by conventional blood measurements and possess prognostic potential. It remains to be determined if this type of metabolic monitoring can find clinical applications in the wide population of septic critically ill patients.

Purpose: Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI., Methods: We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis., Results: We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI., Conclusions: Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis.