Publisher Correction: Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish

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Italian Oncological Pain Survey (IOPS) A Multicentre Italian Study of Breakthrough Pain Performed in Different Settings

Objective: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC). Methods: A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings. Results: 1,412 evaluable cancer patients were enrolled. 53.9% were males and the mean age was 63.7±13.1 years. The mean intensity of background pain was 2.8±0.73. Patients reported 2.4±1.1 BTP episodes/day with a mean intensity of 7.37±1.28. 80.6% patients reported that the BTP had a significant negative impact in everyday life. The majority of patients reported a fast onset of BTP, which was predictable in 50.7% of cases, while BTP with a gradual onset (>10 min) was less predictable (29%) (P=0.001). PCU patients were older, had lower Karnofsky levels, a lower number of BTP episodes/day, a slow onset of BTP onset, and a less predictable BTP. Cancer diagnosis was performed a mean of 23.5 months (SD±32.8) before the assessment. The mean duration of background pain was 3.5 months (SD±3.5), and the mean duration of any analgesic treatment was 2.5 months (SD±3). BTP started a mean of 2.2 months (SD±1.9) before the assessment. Characteristics of BTP were influenced by the course of disease, as well as the duration of background pain and initiation of BTP. Most patients took rapid onset opioids and were satisfied with the treatment. BTP diagnosis was prevalently made by ONC and OPC physicians, and rarely by GPs. Conclusion: This survey performed by an Italian observatory expert review group, has confirmed that the BTP represents a clinically relevant condition with a negative impact on the patient’s quality of life. BTP was detected in all settings involved. A number of factors are associated with the BTP. Also factors regarding the course of disease and setting of care have been assessed. This information may help in stratifying patients or predicting the risk of development of BTP with specific characteristics

Proteína C-reativa não é um marcador útil de infecção em unidade de terapia intensiva cirúrgica

CONTEXT AND OBJECTIVE: C-reactive protein (CRP) is commonly used as a marker for inflammatory states and for early identification of infection. This study aimed to investigate CRP as a marker for infection in patients with postoperative septic shock. DESIGN AND SETTING: Prospective, single-center study, developed in a surgical intensive care unit at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: This study evaluated 54 patients in the postoperative period, of whom 29 had septic shock (SS group) and 25 had systemic inflammatory response syndrome (SIRS group). All of the patients were monitored over a seven-day period using the Sequential Organ Failure Assessment (SOFA) score and daily CRP and lactate measurements. RESULTS: The daily CRP measurements did not differ between the groups. There was no correlation between CRP and lactate levels and the SOFA score in the groups. We observed that the plasma CRP concentrations were high in almost all of the patients. The patients presented an inflammatory state postoperatively in response to surgical aggression. This could explain the elevated CRP measurements, regardless of whether the patient was infected or not. CONCLUSIONS: This study did not show any correlation between CRP and infection among patients with SIRS and septic shock during the early postoperative period.CONTEXTO E OBJETIVO: A proteína C reativa (PCR) é muito usada como marcador de estados inflamatórios e na identificação precoce de infecção. Este estudo teve como proposta investigar a PCR como marcadora de infecção em pacientes em choque séptico no período pós-operatório. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, monocêntrico, desenvolvido numa unidade de terapia intensiva pós-operatória do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foram avaliados 54 pacientes no pós-operatório, sendo 29 deles com choque séptico (grupo SS) e 25 com síndrome da resposta inflamatória sistêmica (grupo SI). Todos os pacientes foram acompanhados durante sete dias pelo escore SOFA (Sequential Organ Failure Assessment) e com dosagens diárias de PCR e lactato. RESULTADOS: As dosagens de PCR não diferiram entre os grupos. Não foi observada correlação entre dosagem de PCR e lactato ou escore SOFA nos grupos estudados. Observamos que as concentrações plasmáticas de PCR estavam elevadas em quase todos os pacientes avaliados. Os pacientes no pós-operatório apresentam estado inflamatório em resposta à agressão cirúrgica, sendo este fato capaz de explicar as dosagens de PCR elevadas, independentemente de o paciente estar ou não infectado. CONCLUSÕES: Este estudo não evidenciou correlação entre PCR e infecção nos pacientes com síndrome da resposta inflamatória sistêmica e choque séptico no período pós-operatório precoce

Systematic versus on-demand early palliative care: A randomised clinical trial assessing quality of care and treatment aggressiveness near the end of life

Aim Early palliative care (EPC) in oncology has shown sparse evidence of a positive impact on patient outcomes, quality of care outcomes and costs. Patients and methods Data for this secondary analysis were taken from a trial of 207 outpatients with metastatic pancreatic cancer randomly assigned to receive standard cancer care plus on-demand EPC (standard arm) or standard cancer care plus systematic EPC (interventional arm). After 20 months\u2019 follow-up, 149 (80%) had died. Outcome measures were frequency, type and timing of chemotherapy administration, use of resources, place of death and overall survival. Results Some indices of end-of-life (EoL) aggressiveness had a favourable impact from systematic EPC. Interventional arm patients showed higher use of hospice services: a significantly longer median and mean period of hospice care (P = 0.025 for both indexes) and a significantly higher median and mean number of hospice admissions (both P < 0.010). In the experimental arm, chemotherapy was performed in the last 30 days of life in a significantly inferior rate with respect to control arm: 18.7% versus 27.8% (adjusted P = 0.036). Other non-significant differences were seen in favour of experimental arm. Conclusions Systematic EPC showed a significant impact on some indicators of EoL treatment aggressiveness. These data, reinforced by multiple non-significant differences in most of the other items, suggest that quality of care is improved by this approach. This study is registered on ClinicalTrials.gov (NCT01996540)

Extracellular vesicles from pluripotent stem cell-derived mesenchymal stem cells acquire a stromal modulatory proteomic pattern during differentiation

Mesenchymal stem/stromal cells (MSCs) obtained from pluripotent stem cells (PSCs) constitute an interesting alternative to classical MSCs in regenerative medicine. Among their many mechanisms of action, MSC extracellular vesicles (EVs) are a potential suitable substitute for MSCs in future cell-free-based therapeutic approaches. Unlike cells, EVs do not elicit acute immune rejection, and they can be produced in large quantities and stored until ready to use. Although the therapeutic potential of MSC EVs has already been proven, a thorough characterization of MSC EVs is lacking. In this work, we used a label-free liquid chromatography tandem mass spectrometry proteomic approach to identify the most abundant proteins in EVs that are secreted from MSCs derived from PSCs (PD-MSCs) and from their parental induced PSCs (iPSCs). Next, we compared both datasets and found that while iPSC EVs enclose proteins that modulate RNA and microRNA stability and protein sorting, PD-MSC EVs are rich in proteins that organize extracellular matrix, regulate locomotion, and influence cell–substrate adhesion. Moreover, compared to their respective cells, iPSCs and iPSC EVs share a greater proportion of proteins, while the PD-MSC proteome appears to be more specific. Correlation and principal component analysis consistently aggregate iPSCs and iPSC EVs but segregate PD-MSC and their EVs. Altogether, these findings suggest that during differentiation, compared with their parental iPSC EVs, PD-MSC EVs acquire a more specific set of proteins; arguably, this difference might confer their therapeutic properties.Fil: la Greca, Alejandro Damián. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Solari, Claudia María. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lombardi, Antonella. Universidad de Buenos Aires; ArgentinaFil: Biani, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aban, Cyntia Estefania. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; ArgentinaFil: Moro, Lucía Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guberman, Alejandra Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Universidad Nacional de La Plata; ArgentinaFil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.</p> <p>Methods</p> <p>review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1^stSeptember, 2006 and 31^stJuly, 2007.</p> <p>Results</p> <p>179 episodes of either primary (<it>n </it>= 117) or secondary (<it>n </it>= 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; <it>p </it>< 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; <it>p </it>= 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (<it>n </it>= 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; <it>p </it>< 0.050).</p> <p>Conclusion</p> <p>In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.</p

Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either gram negative or gram positive bacteria

<p>Abstract</p> <p>Background</p> <p>In the ICU, bacteremia is a life-threatening infection whose prognosis is highly dependent on early recognition and treatment with appropriate antibiotics. Procalcitonin levels have been shown to distinguish between bacteremia and noninfectious inflammatory states accurately and quickly in critically ill patients. However, we still do not know to what extent the magnitude of PCT elevation at the onset of bacteremia varies according to the Gram stain result.</p> <p>Methods</p> <p>Review of the medical records of every patient treated between May, 2004 and December, 2006 who had bacteremia caused by either Gram positive (GP) or Gram negative (GN) bacteria, and whose PCT dosage at the onset of infection was available.</p> <p>Results</p> <p>97 episodes of either GN bacteremia (<it>n </it>= 52) or GP bacteremia (<it>n </it>= 45) were included. Procalcitonin levels were found to be markedly higher in patients with GN bacteremia than in those with GP bacteremia, whereas the SOFA score value in the two groups was similar. Moreover, in the study population, a high PCT value was found to be independently associated with GN bacteremia. A PCT level of 16.0 ng/mL yielded an 83.0% positive predictive value and a 74.0% negative predictive value for GN-related bacteremia in the study cohort (AUROCC = 0.79; 95% CI, 0.71–0.88).</p> <p>Conclusion</p> <p>In a critically ill patient with clinical sepsis, GN bacteremia could be associated with higher PCT values than those found in GP bacteremia, regardless of the severity of the disease.</p

Symptoms of gastroesophageal reflux disease in severely mentally retarded people: a systematic review

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease (GERD) occurs when stomach acid frequently backs up (or refluxes) into the gullet (or esophagus), and it has serious consequences for the quality of life. Usually this is felt as heartburn. Because severely mentally retarded people usually do not utter complaints of heartburn, it requires a high index of suspicion to discover possible GERD. Therefore it is relevant for care professionals such as nurses to have knowledge of those with a higher risk of GERD and of the possible manifestations of GERD.</p> <p>Methods</p> <p>Using a predefined search method, electronic databases were searched for studies relating the presence of symptoms to the presence of GERD. Relevant data were extracted and the methodological quality of the studies assessed. The results of the included studies were synthesized and conclusions about the level of evidence were drawn.</p> <p>Results</p> <p>Nineteen studies were found relating symptoms to the presence of GERD. Only four were of good methodological quality. The studies were very diverse concerning the studied population, the study method, and the kind of symptoms examined. This makes it difficult to synthesize the results of the studies. There is evidence that patients with cerebral palsy, patients using anticonvulsive drugs, and those with an IQ lower than 35 more frequently have GERD. There is also evidence that vomiting, rumination and hematemesis are associated with a higher risk of the presence of GERD, whereas there is no clear scientific evidence that particular behavior symptoms are indicative for GERD.</p> <p>Conclusion</p> <p>The possible manifestations of GERD are many and varied. A guideline will be made for care professionals to aid systematic observation of possible manifestations of GERD.</p

Toward an operative diagnosis in sepsis: a latent class approach

<p>Abstract</p> <p>Background</p> <p>Recent data have suggested that 18 million of new sepsis cases occur each year worldwide, with a mortality rate of almost 30%. There is not consensus on the clinical definition of sepsis and, because of lack of training or simply unawareness, clinicians often miss or delay this diagnosis. This is especially worrying; since there is strong evidence supporting that early treatment is associated with greater clinical success. There are some difficulties for sepsis diagnosis such as the lack of an appropriate gold standard to identify this clinical condition. This situation has hampered the assessment of the accuracy of clinical signs and biomarkers to diagnose sepsis.</p> <p>Methods/design</p> <p>Cross-sectional study to determine the operative characteristics of three biological markers of inflammation and coagulation (D-dimer, C-reactive protein and Procalcitonin) as diagnostic tests for sepsis, in patients admitted to hospital care with a presumptive infection as main diagnosis.</p> <p>Discussion</p> <p>There are alternative techniques that have been used to assess the accuracy of tests without gold standards, and they have been widely used in clinical disciplines such as psychiatry, even though they have not been tested in sepsis diagnosis. Considering the main importance of diagnosis as early as possible, we propose a latent class analysis to evaluate the accuracy of three biomarkers to diagnose sepsis.</p