Methods of Assessing Frailty in the Critically Ill: A Systematic Review of the Current Literature.

INTRODUCTION: As new treatments have become established, more frail pre-ICU patients are being admitted to intensive care units (ICUs); this is creating new challenges to provide adequate care and to ensure that resources are allocated in an ethical and economical manner. This systematic review evaluates the current standard for assessing frailty on the ICU, including methods of assessment, time point of measurements, and cut-offs. METHODS: A systematic search was conducted on MEDLINE, Clinical Trials, Cochrane Library, and Embase. Randomized and non-randomized controlled studies were included that evaluated diagnostic tools and ICU outcomes for frailty. Exclusion criteria were the following: studies without baseline assessment of frailty on ICU admission, studies in paediatric patients or pregnant women, and studies that targeted very narrow populations of ICU patients. Eligible articles were included until January 31, 2021. Methodological quality was assessed using the Newcastle-Ottawa Scale. No meta-analysis was performed, due to heterogeneity. RESULTS: N = 57 articles (253,376 patients) were included using 19 different methods to assess frailty or a surrogate. Frailty on ICU admission was most frequently detected using the Clinical Frailty Scale (CFS) (n = 35, 60.3%), the Frailty Index (n = 5, 8.6%), and Fried's frailty phenotype (n = 6, 10.3%). N = 22 (37.9%) studies assessed functional status. Cut-offs, time points, and manner of baseline assessment of frailty on ICU admission varied widely. Frailty on ICU admission was associated with short- and long-term mortality, functional and cognitive impairment, increased health care dependency, and impaired quality of life post-ICU discharge. CONCLUSIONS: Frailty assessment on the ICU is heterogeneous with respect to methods, cut-offs, and time points. The CFS may best reflect frailty in the ICU. Frailty assessments should be harmonized and performed routinely in the critically ill.

Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies. DATA SOURCES: A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. STUDY SELECTION AND DATA EXTRACTION: All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews. DATA SYNTHESIS: A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03-19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51-3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55-5.00) and 1.39 (95% CI, 1.15-1.69) for cumulative fluid balance. Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75-2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81-7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39-1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30-5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03-1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11-1.28) per liter increase in positive fluid balance. CONCLUSIONS: This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.

Understanding Refugees' Health.

According to the United Nations Refugee Agency (UNHCR), 65.6 million people have been forcibly displaced worldwide. Several factors have a major influence on asylum seekers' health; so, their health profile is markedly different from that of the population in the country of asylum. The aim of this study is to review the major issues physicians need to be aware of when treating asylum seekers, with a special focus on the neurological problems of asylum seekers and refugees. The major impact factors on refugees' health are linked to experiences and exposure (1) in the country of origin, (2) in refugee camps and en route to Europe, and (3) in the process of immigration into the host country and living in European asylum centers. Refugees' health is also affected by psychological problems and by infectious diseases. Additionally, chronic diseases resulting in polymorbidity, cancer, and neurological diseases are easy to overlook and demand special attention. Neurological injuries/diseases may be traumatic (e.g., spinal cord injuries), posttraumatic (e.g., chronic pain syndromes), the result of cerebral infections, or the consequences of starvation (e.g., epilepsy, ataxia, and paraesthesia). The main challenges for physicians are lack of awareness of the asylum seekers' specific health care problems, language and intercultural communication problems, as well as access and integration of asylum seekers into the health care system. The health issues of asylum seekers are manifold and challenging to physicians. Awareness of these conditions is mandatory to ensure good clinical practice for this patient population, which has a huge burden in chronic, infectious, mental, and neurological diseases.

Gastrointestinal parasites of Peltocephalus dumerilianus (Testudines: Podocnemididae) from Jaú National Park, Brazilian Amazon.

The big-headed Amazon River turtle, Peltocephalus dumerilianus, is endemic to the Orinoco and Amazon River basins. It is a food source for local communities, often unsustainably. Knowledge about P. dumerilianus' parasitological fauna and host-parasite relationships is limited. Thus, ecological aspects of gastrointestinal parasitism in this species were investigated. Helminths were found in the gastrointestinal tract of 21 turtles, morphologically identified, and infection descriptors calculated. All animals harbored helminths: nematodes Ancyracanthus pinnatifidus, Paratractis hystrix, Atractis trematophila, Klossinemella conciliatus indeterminate three Klossinemella species, and digeneans Nematophila grandis, Helicotrema spirale, and Telorchis hagmanni. The highest parasite load occurred in the large intestine, followed by the small intestine and stomach. Shell length directly correlated with parasite burden of heteroxenic helminths, with males having higher burden than females. This is the first record of A. trematophila, K. conciliatus, and T. hagmanni in P. dumerilianus, and new location record for A. trematophila, P. hystrix, N. grandis, H. spirale, and T. hagmanni. Three potentially new Klossinemella species are presented.

Fluid accumulation syndrome in sepsis and septic shock: pathophysiology, relevance and treatment-a comprehensive review.

In this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagnosis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS) is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes. While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis, monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock, including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics, or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resuscitation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, maintenance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings.Trial registration: Not applicable.

Toxoplasma gondii and Neospora caninum in invasive wild boars (Sus scrofa) and hunting dogs from Brazil.

The wild boar, an impactful invasive species in Brazil, is subject to population control activities, which often include the use of hunting dogs. Hunters commonly consume wild boar meat, which is also used to feed their dogs, posing a risk of Toxoplasma gondii infection for humans and both T. gondii and Neospora caninum for dogs. The study aimed to investigate the prevalence of infection in wild boars (n = 127) and hunting dogs (n = 73) from São Paulo, Rio Grande do Sul, and Paraná states. We employed histopathological, serological (indirect fluorescent antibody test), and molecular techniques (endpoint polymerase chain reaction). Histopathology slides of wild boar tissue (central nervous system, heart, skeletal muscle, liver, spleen, kidney, gastrointestinal tract, pancreas, lymph nodes, and thyroid) sections revealed no T. gondii or N. caninum cysts (0/47). Antibodies anti-T. gondii were detected in 35/108 (32.4%) and anti-N. caninum in 45/108 (41.7%) wild boars. Only 2/18 (11.1%) wild boar tissue homogenate samples tested positive for T. gondii on endpoint PCR. Hunting dogs showed antibodies against T. gondii in 62/73 (85%) and against N. caninum in 31/73 (42%). The presence of antibodies against T. gondii and N. caninum in wild boars and hunting dogs, along with T. gondii DNA detection in wild boars, indicates the circulation of these parasites. Educating hunters on preventing these foodborne diseases, including zoonotic risks, is crucial.

Rabies Virus-Neutralizing Antibodies in Free-Ranging Invasive Wild Boars (Sus scrofa) from Brazil.

Rabies, one of the most lethal global zoonoses, affects all mammals. It remains circulating worldwide in sylvatic cycles through terrestrial and airborne reservoirs, and in Brazil, bats are currently the main reservoirs and source of transmission. Wild boars, an important invasive alien species in Brazil, are a proven food source for hematophagous bats and may participate in the Brazilian sylvatic cycle of rabies. We evaluated the presence of this pathogen in hunted wild boars from the São Paulo state using histopathology, the direct fluorescent antibody test (DFA), viral isolation in cell culture (VICC), the rapid fluorescent focus inhibition test (RFFIT), and quantitative reverse transcription polymerase chain reaction (RT-qPCR). The results of histopathological, DFA, VICC, and RT-qPCR analysis were negative for all samples; seven serum samples tested positive in the RFFIT, and titers ranged from 0.13 IU/mL to 0.5 IU/mL. The presence of rabies virus-neutralizing antibodies in the studied wild boars suggests the circulation of the virus in these animals. Educative actions directed at hunters should include information on the prevention of this important zoonosis.

Sexual activity-related emergency department admissions: eleven years of experience at a Swiss university hospital.

PRINCIPALS: Most people enjoy sexual intercourse without complications, but a significant, if small, number need to seek emergency medical help for related health problems. The true incidence of these problems is not known. We therefore assessed all admissions to our emergency department (ED) in direct relation to sexual intercourse. METHODS: All data were collected prospectively and entered into the ED's centralised electronic patient record database (Qualicare, Switzerland) and retrospectively analysed. The database was scanned for the standardised key words: 'sexual intercourse' (German 'Geschlechtsverkehr') or 'coitus' (German 'Koitus'). RESULTS: A total of 445 patients were available for further evaluation; 308 (69.0%) were male, 137 (31.0%) were female. The median age was 32 years (range 16-71) for male subjects and 30 years (range 16-70) for female subjects. Two men had cardiovascular emergencies. 46 (10.3%) of our patients suffered from trauma. Neurological emergencies occurred in 55 (12.4%) patients: the most frequent were headaches in 27 (49.0%), followed by subarachnoid haemorrhage (12, 22.0%) and transient global amnesia (11, 20.0%). 154 (97.0%) of the patients presenting with presumed infection actually had infections of the urogenital tract. The most common infection was urethritis (64, 41.0%), followed by cystitis (21, 13.0%) and epididymitis (19, 12.0%). A sexually transmitted disease (STD) was diagnosed in 43 (16.0%) of all patients presenting with a presumed infection. 118 (43.0%) of the patients with a possible infection requested testing for an STD because of unsafe sexual activity without underlying symptoms. CONCLUSIONS: Sexual activity is mechanically dangerous, potentially infectious and stressful for the cardiovascular system. Because information on ED presentation related to sexual intercourse is scarce, more efforts should be undertaken to document all such complications to improve treatment and preventative strategies.

Epidemiology and Integrative Taxonomy of Helminths of Invasive Wild Boars, Brazil.

Wild boars (Sus scrofa) are a significant invasive species in Brazil. We evaluated the helminth diversity of 96 wild boars in São Paulo state. Helminth infection descriptors were calculated, the species were identified and their 18S, 28S rDNA and internal transcribed spacer (ITS) regions were amplified for phylogenetic analyses. Ascarops strongylina, Strongyloides ransomi, Globocephalus urosubulatus, Oesophagostomum dentatum, Trichuris suis, Metastrongylus salmi, Metastrongylus pudendotecus, Ascaris suum and Stephanurus dentatus and Macracanthorhynchus hirudinaceus were identified. Globocephalus urosubulatus had the highest prevalence and mean abundance, and most animals had mixed infections with three parasite species. There was no association between parasite intensity and prevalence and host sex and body condition index (p > 0.05). Novel DNA sequences were obtained from G. urosubulatus, A. strongylina, and S. dentatus. This is the first study on the helmint diversity of non-captive wild boars in Brazil, and the first report of the occurrence of M. hirudinaceus, G. urosubulatus and S. dentatus in Brazilian wild boars. Non-captive wild boars of São Paulo State did not act as capture hosts for native helminth species but maintained their typical parasites, common to domestic pigs. They may act as parasite dispersers for low-tech subsistence pig farming and for native Tayassuidae.

Endoparasites of marsupials in fragments of the Atlantic rainforest, western Paraná State, Brazil.

Knowledge of taxonomy and biodiversity of parasites is fundamental to better understand ecosystem dynamics. The objective of this study was to describe the helminth fauna of two species of marsupials in five fragments of the Atlantic rainforest in the western region of Paraná State, Brazil. In a total of 4050 trap-nights, the animals were captured using Sherman, Tomahawk, and Pitfall traps, euthanized, necropsied, and their organs inspected for helminths. After identification of the parasites, descriptors of infection, such as prevalence, mean abundance, mean intensity, and range of intensity, were calculated. Collectively, six helminth species were observed in 18 animals. The following five species were observed in Marmosa paraguayana: Viannaia hamata (58.8%), Gracilioxyuris agilisis (52.9%), Travassostrongylus sextus (17.6%), Oncicola luehei (5.9%), and Pritchardia boliviensis (5.9%). Whereas the following two species were observed in Monodelphis dimidiata: Trichohelix tuberculata (100%) and Travassostrongylus sextus (100%). This study represents a new locality record for all helminths described herein, and a new host for four helminth species. This is the first report on the helminth fauna of Monodelphis dimidiata, expanding knowledge about marsupials in the Brazilian Atlantic Forest.

Integrative taxonomy of Metastrongylus spp. in wild boars from Brazil.

BACKGROUND: Wild boars (Sus scrofa) may cause substantial damage to crops and can spread zoonotic parasites to domestic animals, posing a risk to health and animal production. Metastrongylus spp. can negatively affect the wild boar population, increasing piglet mortality. In addition to that, studies with Metastrongylus genetic characterization are still scarce in Brazil. The present study aims to characterize Metastrongylus spp. from wild boars hunted in the states of São Paulo, Paraná, and Rio Grande do Sul, Brazil, using traditional morphological description and DNA sequences in an integrative taxonomic approach. METHODS: After nematode collection from 58 wild boars, the parasites were morphologically identified and genetically characterized by the amplification of 18S ribosomal DNA (rDNA), 28S rDNA, internal transcribed spacer (ITS) region, and cox-1 mitochondrial DNA (mtDNA). Descriptors of infection were determined and Pearson's Chi-square test was applied to compare the prevalence of infections among the identified parasite species, host age group (juveniles and adults), and sex. The Mann-Whitney U test was performed to compare the mean intensity between the age groups and sex. RESULTS: Metastrongylus salmi, Metastrongylus apri, and Metastrongylus pudendotectus were identified in 77.6% (45/58) of the necropsied wild boars. Metastrongylus salmi was the most prevalent and abundant species (70.7%, 11.1), followed by M. pudendotectus (18.9%, 4.3) and M. apri (17.2%, 2.2). Metastrongylus pudendotectus showed the highest mean intensity and range (25.2, 1-93), followed by M. salmi (15.7, 1-58) and M. apri (12.6, 3-27). We found a significantly higher prevalence of Metastrongylus spp. and M. salmi in adult wild boars, probably associated with a more prolonged time of exposure to intermediate host species. The phylogenetic analysis revealed that ITS2 region and cox-1 mtDNA are the most suitable genetic markers for Metastrongylus species characterization. Genetic variability between M. apri and M. salmi isolates was verified. CONCLUSIONS: We expand the knowledge about the Metastrongylus community in the non-captive wild boar population from Brazil as well as the importance of this exotic species in the maintenance of Metastrongylus spp. in its areas of occurrence. The novel genetic sequences obtained may help further studies to understand the genetic diversity in other nematode populations from Brazil and other countries.

Gender distribution in boards of intensive care medicine societies.

PURPOSE: The established gender gap in intensive care medicine is larger compared to other medical specialties. The aim of this study was to evaluate gender distribution in boards of intensive care medicine societies worldwide. METHODS: In this cross-sectional analysis, board members and presidents of all intensive care medicine societies associated with the European Society of Intensive Care Medicine were eligible for study inclusion. Exclusion criteria were: A) society without focus on intensive care and B) online information unavailable. RESULTS: In 2021, 65 presidents and 820 board members were analyzed. Ten presidents (15%) and 231 board members (28%) were women. The proportion of women presidents reached from 0% in Africa to 20% in Europe and South America. The proportion of women board members was highest in North and South America with 42% and 46% respectively and lowest in Africa (21%) and Asia (10%). In Europe, 31% of board members were women and 35% in Australia/New Zealand. Among presidents, women were underrepresented in all continents while gender distribution among board members varied significantly between countries (p < 0.0001). CONCLUSION: Our analysis reveals an inequality in gender distribution in the boards of national intensive care medicine societies which varies but persists for all global regions.

Reproductive Justice: A Case-Based, Interactive Curriculum.

Introduction: Reproductive injustices such as forced sterilization, preventable maternal morbidity and mortality, restricted access to family planning services, and policy-driven environmental violence undermine reproductive autonomy and health outcomes, with disproportionate impact on historically marginalized communities. However, curricula focused on reproductive justice (RJ) are lacking in medical education. Methods: We designed a novel, interactive, case-based RJ curriculum for postclerkship medical students. This curriculum was created using published guidelines on best practices for incorporating RJ in medical education. The session included a prerecorded video on the history of RJ, an article, and four interactive cases. Students engaged in a 2-hour small-group session, discussing key learning points of each case. We evaluated the curriculum's impact with a pre- and postsurvey and focus group. Results: Sixty-eight students participated in this RJ curriculum in October 2020 and March 2021. Forty-one percent of them completed the presurvey, and 46% completed the postsurvey. Twenty-two percent completed both surveys. Ninety percent of respondents agreed that RJ was relevant to their future practice, and 87% agreed that participating in this session would impact their clinical practice. Most respondents (81%) agreed that more RJ content is needed. Focus group participants appreciated the case-based, interactive format and the intersectionality within the cases. Discussion: This interactive curriculum is an innovative and effective way to teach medical students about RJ and its relevance to clinical practice. Walking alongside patients as they accessed reproductive health care in a case-based curriculum improved students' comfort and self-reported knowledge on several RJ topics.

Prevalence and Factors Associated With Syphilis in People Living With HIV/AIDS in the State of Pará, Northern Brazil.

Syphilis continues to be a public health problem worldwide and its incidence has increased in people living with HIV/AIDS in recent years. This study determined the prevalence and factors associated with syphilis in people living with HIV/AIDS in the city of Belém, northern Brazil. A cross-sectional study was conducted from June to November 2018. A total of 500 people living with HIV/AIDS attended at a specialized unit of the public health network of the State of Pará were studied. Questionnaires were used to collect socio-demographic data and potential risk factors for syphilis. Blood samples were collected from all subjects and screened for syphilis using VDRL, and the seropositive were confirmed using FTA-abs. Logistic regressions were used to identify the factors associated with syphilis. Most subjects were male (56.8%), had more than 40 years (54.0%), single (63.0%), had finished high school (54.2%), had monthly income ≤1 minimum wage (72.4%), and had been born to the city of Belém (59.8%). Prevalence of syphilis was 6.4%. Eight characteristics/behaviors associated with syphilis: male, young adults, single, studied at least high school, monthly income >1 minimum wage, homosexual/bisexual, does not use or sporadically use condoms during sexual intercourse, and have had more than one sexual partner in the last three months. The prevalence of syphilis in people living with HIV/AIDS in Belém is low when compared to other Brazilian states. However, there is a need for public policies and actions to monitor, control and prevent these two sexually transmitted infections.

Severe acute respiratory distress syndrome (ARDS) induced by human adenovirus B21: Report on 2 cases and literature review.

Severe pneumonia and ARDS caused by human adenovirus B21 infections (HAdV-B21) is a rare, but a devastating disease with rapid progression to multiorgan failure and death. However, only a few cases were reported so far. Infections appear associated with increased disease severity and higher mortality in infected critically ill patients. Possible factors contributing to infection are underlying psychiatric disease resulting in institutionalization of respective patients, and polytoxicomania. Controlled data on the therapy of severe adenovirus infections are lacking and remains experimental. In conclusion, data on HAdV-B21 infections causing severe pneumonia or ARDS are scarce. Controlled clinical trials on the therapy of adenovirus pneumonia are non existent and thus there is no established therapy so far. ICU physicians should be aware of this potentially devastating disease and further studies are needed.

Endoparasites of marsupials in fragments of the Atlantic rainforest, western Paraná State, Brazil / Endoparasitas de marsupiais em fragmentos de Mata Atlântica no oeste do Estado do Paraná, Brasil

Abstract Knowledge of taxonomy and biodiversity of parasites is fundamental to better understand ecosystem dynamics. The objective of this study was to describe the helminth fauna of two species of marsupials in five fragments of the Atlantic rainforest in the western region of Paraná State, Brazil. In a total of 4050 trap-nights, the animals were captured using Sherman, Tomahawk, and Pitfall traps, euthanized, necropsied, and their organs inspected for helminths. After identification of the parasites, descriptors of infection, such as prevalence, mean abundance, mean intensity, and range of intensity, were calculated. Collectively, six helminth species were observed in 18 animals. The following five species were observed in Marmosa paraguayana: Viannaia hamata (58.8%), Gracilioxyuris agilisis (52.9%), Travassostrongylus sextus (17.6%), Oncicola luehei (5.9%), and Pritchardia boliviensis (5.9%). Whereas the following two species were observed in Monodelphis dimidiata: Trichohelix tuberculata (100%) and Travassostrongylus sextus (100%). This study represents a new locality record for all helminths described herein, and a new host for four helminth species. This is the first report on the helminth fauna of Monodelphis dimidiata, expanding knowledge about marsupials in the Brazilian Atlantic Forest.

Resumo Conhecimentos taxonômicos e da biodiversidade parasitária são fundamentais para uma melhor compreensão da dinâmica do ecossistema. O objetivo do estudo foi descrever a helmintofauna de marsupiais em cinco fragmentos de Mata Atlântica, na região Oeste do Estado do Paraná, Brasil. Em um total de 4.050 armadilhas/noite, os animais foram capturados com as do tipo Sherman, Tomahawk e Pitfall, eutanasiados, necropsiados e seus órgãos inspecionados em busca de helmintos. Após a identificação do parasita, foram calculados os indicadores de infecção (prevalência, abundância média, intensidade média e variação de intensidade). Seis espécies de helmintos foram observadas em dezoito animais; cinco em Marmosa paraguayana: Viannaia hamata (58,8%), Gracilioxyuris agilisis (52,9%), Travassostrongylus sextus (17,6%), Oncicola luehei (5,9%) e Pritchardia boliviensis (5,9%), e duas em Monodelphis dimidiata: Trichohelix tuberculata (100%) e Travassostrongylus sextus (100%). Este estudo representa um novo registro de localidade para todos os helmintos descritos e um novo hospedeiro para quatro deles. Trata-se do primeiro relato da helmintofauna de Monodelphis dimidiata, expandindo-se os conhecimentos sobre marsupiais na mata Atlântica brasileira.

Hypertonic saline in critical illness - A systematic review.

INTRODUCTION: The optimal approach to fluid management in critically ill patients is highly debated. Fluid resuscitation using hypertonic saline was used in the past for more than thirty years, but has recently disappeared from clinical practice. Here we provide an overview on the currently available literature on effects of hypertonic saline infusion for fluid resuscitation in the critically ill. METHODS: Systematic analysis of reports of clinical trials comparing effects of hypertonic saline as resuscitation fluid to other available crystalloid solutions. A literature search of MEDLINE and the Cochrane Controlled Clinical trials register (CENTRAL) was conducted to identify suitable studies. RESULTS: The applied search strategy produced 2284 potential publications. After eliminating doubles, 855 titles and abstracts were screened and 40 references retrieved for full text analysis. At total of 25 scientific studies meet the prespecified inclusion criteria for this study. CONCLUSION: Fluid resuscitation using hypertonic saline results in volume expansion and less total infusion volume. This may be of interest in oedematous patients with intravascular volume depletion. When such strategies are employed, renal effects may differ markedly according to prior intravascular volume status. Hypertonic saline induced changes in serum osmolality and electrolytes return to baseline within a limited period in time. Sparse evidence indicates that resuscitation with hypertonic saline results in less perioperative complications, ICU days and mortality in selected patients. In conclusion, the use of hypertonic saline may have beneficial features in selected critically ill patients when carefully chosen. Further clinical studies assessing relevant clinical outcomes are warranted.

Assessment of immune organ dysfunction in critical illness: utility of innate immune response markers.

In critically ill patients, organ dysfunctions are routinely assessed, monitored, and treated. Mounting data show that substantial critical illness-induced changes in the immune system can be observed in most ICU patients and that not only "hyper-inflammation" but also persistence of an anti-inflammatory phenotype (as in sepsis-associated immunosuppression) is associated with increased morbidity and mortality. Despite common perception, changes in functional immunity cannot be adequately assessed by routine inflammatory biomarkers such as C-reactive protein, procalcitonin, or numerical analysis of leukocyte (sub)-counts. Cytokines appear also not suited due to their short half-life and pleiotropy, their unexclusive origin from immune cells, and their potential to undergo antagonization by circulating inactivating molecules. Thus, beyond leukocyte quantification and use of routine biomarkers, direct assessment of immune cell function seems required to characterize the immune systems' status. This may include determination of, e.g., ex vivo cellular cytokine release, phagocytosis activity, and/or antigen-presenting capacity. In this regard, standardized flow-cytometric assessment of the major histocompatibility-II complex human leukocyte antigen (-D related) (HLA-DR) has gained particular interest. Monocytic HLA-DR (mHLA-DR) controls the interplay between innate and adaptive immunity and may serve as a "global" biomarker of injury-associated immunosuppression, and its decreased expression is associated with adverse clinical outcomes (e.g., secondary infection risk, mortality). Importantly, recent data demonstrate that injury-associated immunosuppression can be reversed-opening up new therapeutic avenues in affected patients. Here we discuss the potential scientific and clinical value of assessment of functional immunity with a focus on monocytes/macrophages and review the current state of knowledge and potential perspectives for affected critically ill patients.