Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Lung cancer in Argentina: a modelling study of disease and economic burden.

OBJECTIVES: Lung cancer remains a significant global public health challenge and is still one of the leading causes of cancer-related death in Argentina. This study aims to assess the disease and economic burden of lung cancer in the country. STUDY DESIGN: Burden of disease study. METHODS: A mathematical model was developed to estimate the disease burden and direct medical cost attributable to lung cancer. Epidemiological parameters were obtained from local statistics, the Global Cancer Observatory, the Global Burden of Disease databases, and a literature review. Direct medical costs were estimated through micro-costing. Costs were expressed in US dollars (US$), April 2023 (1 US$ = 216.38 Argentine pesos). A second-order Monte Carlo simulation was performed to estimate the uncertainty. RESULTS: Considering approximately 10,000 deaths, 12,000 incident cases, and 14,000 5-year prevalent cases, the economic burden of lung cancer in Argentina in 2023 was estimated to be US$ 556.20 million (396.96-718.20), approximately 1.4% of the total healthcare expenditure for the country. The cost increased with a higher stage of the disease, and the main driver was drug acquisition (80%). A total of 179,046 disability-adjusted life years could be attributable to lung cancer, representing 10% of the total cancer. CONCLUSION: The disease and economic burden of lung cancer in Argentina implies a high cost for the health system and would represent 19% of the previously estimated economic burden for 29 cancers in Argentina.

Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B.

Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains.IMPORTANCE FMDV nonstructural protein 2B is able to insert itself into cellular membranes to form a pore. This pore allows the passage of ions and small molecules through the membrane. In this study, we were able to show that both current and small molecules are able to pass though the pore made by 2B. We also discovered for the first time a virus with a pore-forming protein that contains two independent functional pores. By making mutations in our infectious clone of FMDV, we determined that mutations in either pore resulted in nonviable virus. This suggests that both pore-forming functions are independently required during FMDV infection.

Diagnosing pulmonary embolisms: the clinician's point of view. / Diagnóstico de la embolia pulmonar. El punto de vista del médico clínico.

Pulmonary thromboembolism is common and potentially severe. To ensure the correct approach to the diagnostic workup of pulmonary thromboembolism, it is essential to know the basic concepts governing the use of the different tests available. The diagnostic approach to pulmonary thromboembolism is an example of the application of the conditional probabilities of Bayes' theorem in daily practice. To interpret the available diagnostic tests correctly, it is necessary to analyze different concepts that are fundamental for decision making. Thus, it is necessary to know what the likelihood ratios, 95% confidence intervals, and decision thresholds mean. Whether to determine the D-dimer concentration or to do CT angiography or other imaging tests depends on their capacity to modify the pretest probability of having the disease to a posttest probability that is higher or lower than the thresholds for action. This review aims to clarify the diagnostic sequence of thromboembolic pulmonary disease, analyzing the main diagnostic tools (clinical examination, laboratory tests, and imaging tests), placing special emphasis on the principles that govern evidence-based medicine.

Coagulation profiles of unexpected DCDD donors do not indicate a role for exogenous fibrinolysis.

It has been suggested that vascular stasis during cardio-circulatory arrest leads to the formation of microvascular thrombi and the viability of organs arising from donation after circulatory determination of death (DCDD) donors may be improved through the application of fibrinolytic therapy. Our aim was to comprehensively study the coagulation profiles of Maastricht category II DCDD donors in order to determine the presence of coagulation abnormalities that could benefit from fibrinolytic therapy. Whole blood from potential DCDD donors suffering out-of-hospital cardiac arrest was sampled after declaration of death in the emergency department, and rotational thromboelastomeric analysis was performed. Between July 2012 and December 2013, samples from 33 potential DCDD donors were analyzed. All patients demonstrated hyperfibrinolysis (HF), as reflected by maximum clot lysis of 98-100% in all cases, indicating that there is no role for additional fibrinolytic therapy in this setting. As well, we observed correlations between thromboelastomeric lysis parameters and maximum hepatic transaminase levels measured in potential donors and renal artery flows measured during ex situ hypothermic oxygenated machine perfusion, indicating that further studies on the utility of thromboelastometry to evaluate organ injury and perhaps even viability in unexpected DCDD may be warranted.

Regulatory role of PI3K-protein kinase B on the release of interleukin-1ß in peritoneal macrophages from the ascites of cirrhotic patients.

Great effort has been paid to identify novel targets for pharmaceutical intervention to control inflammation associated with different diseases. We have studied the effect of signalling inhibitors in the secretion of the proinflammatory and profibrogenic cytokine interleukin (IL)-1ß in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients and compared with those obtained from the blood of healthy donors. Peritoneal M-DM were isolated from non-infected ascites of cirrhotic patients and stimulated in vitro with lipopolysaccharide (LPS) and heat-killed Candida albicans in the presence or absence of inhibitors for c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 1 (MEK1), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). The IL1B and CASP1 gene expression were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of IL-1ß and caspase-1 were determined by Western blot. IL-1ß was also assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Results revealed that MEK1 and JNK inhibition significantly reduced the basal and stimulated IL-1ß secretion, while the p38 MAPK inhibitor had no effect on IL-1ß levels. On the contrary, inhibition of PI3K increased the secretion of IL-1ß from stimulated M-DM. The activating effect of PI3K inhibitor on IL-1ß release was mediated mainly by the enhancement of the intracellular IL-1ß and caspase-1 content release to the extracellular medium and not by increasing the corresponding mRNA and protein expression levels. These data point towards the role of MEK1 and JNK inhibitors, in contrast to the PI3K-protein kinase B inhibitors, as potential therapeutic tools for pharmaceutical intervention to diminish hepatic damage by reducing the inflammatory response mediated by IL-1ß associated with liver failure.

[Non-invasive ventilation improves comfort in pediatric palliative care patients]. / La ventilación no invasiva mejora el confort al paciente paliativo pediátrico.

OBJECTIVE: To analyze the appropriate use of non-invasive ventilation and its contribution to improving comfort in pediatric palliative care patients. PATIENTS AND METHOD: This is a descriptive cross-sectional study comprising 55 palliative care patients from San Juan de Dios Hospital in Barcelona. The effectiveness was evaluated using a register of socio-demographic, clinical-ventilatory and oxymetric parameters, the comfort and dyspnea's grade using Silverman Anderson scale, and pain level using pediatric scales. RESULTS: The effectiveness of the technique was proved by a decreased heart rate (133.53±25.8 vs. 111.04±23.1; p<0.0001), respiratory rate (35.02±12.9 vs. 25.63±5.7; p<0.0001) and an increase of partial oxygen saturation (95.7±2.9 vs. 96.87±7.2; p<0.0001) and partial oxygen saturation/fraction of inspired oxygen ratio (297.12±113.4 vs. 336.97±100.7; p<0.0001). Dyspnea and pain levels improved in 100% of the patients. CONCLUSIONS: The therapy was effective and the comfort improved in 100% of the patients.

[Kidney transplantation in children weighing 11 kg or less]. / Trasplante renal en el paciente con peso igual o menor a 11 kg.

AIMS OF THE STUDY: To evaluate the outcome of kidney transplantation in children with low weight. METHODS: Retrospective review of the medical records of patients weighing 11 kg or less that received kidney transplantation between 2001 and 2013 were retrospectively reviewed. RESULTS: Fifty-nine kidney transplantations were performed in pediatric patients in our center, 12 of them were performed in patients weighing 11 kg or less (20%). The mean age of the recipient at the time of transplantation was 2 years (1-3.5); the mean weight was 9.4 ± 1.1 kg (8.3-11). The etiology of kidney failure was malformative in 42% of patients, inherited in 33%, glomerular in 8% and oiler etiologies in 17% of the patients. Two patients did not receive replacement therapy before transplantation (16.7%), nine received peritoneal dialysis (75%) and one of them hemodialysis (8.3%). Eleven of the grafts were from cadaveric donor (91.7%) and one of them from a living donor (8.3%). The mean donor age was 10 years (0.5-29). There was one case of acute graft thrombosis (8.3%) and one case of eventration requiring reoperation; there were no other major complications. Mean follow-up was 59 months (4-130). Overall survival (OS) was 100% at 1 year and 91.7% at 5 years. There was one death in a patient with mitochondrial disease with a functioning graft. Graft survival (GS) was 92% at 1 year and 75% at 5 years. CONCLUSION: Kidney transplantation is the treatment of choice for end-stage kidney failure in the young child. It provides good results in terms of patient and graft survival.

Linking pesticide exposure to neurodegenerative diseases: An in vitro investigation with human neuroblastoma cells.

Although many organochlorine pesticides (OCPs) have been banned or restricted because of their persistence and linkage to neurodegenerative diseases, there is evidence of continued human exposure. In contrast, registered herbicides are reported to have a moderate to low level of toxicity; however, there is little information regarding their toxicity to humans or their combined effects with OCPs. This study aimed to characterize the mechanism of toxicity of banned OCP insecticides (aldrin, dieldrin, heptachlor, and lindane) and registered herbicides (trifluralin, triallate, and clopyralid) detected at a legacy contaminated pesticide manufacturing and packing site using SH-SY5Y cells. Cell viability, LDH release, production of reactive oxygen species (ROS), and caspase 3/7 activity were evaluated following 24 h of exposure to the biocides. In addition, RNASeq was conducted at sublethal concentrations to investigate potential mechanisms involved in cellular toxicity. Our findings suggested that aldrin and heptachlor were the most toxic, while dieldrin, lindane, trifluralin, and triallate exhibited moderate toxicity, and clopyralid was not toxic to SH-SY5Y cells. While aldrin and heptachlor induced their toxicity through damage to the cell membrane, the toxicity of dieldrin was partially attributed to necrosis and apoptosis. Moreover, toxic effects of lindane, trifluralin, and triallate, at least partially, were associated with ROS generation. Gene expression profiles suggested that decreased cell viability induced by most of the tested biocides was related to inhibited cell proliferation. The dysregulation of genes encoding for proteins with anti-apoptotic properties also supported the absence of caspase activation. Identified enriched terms showed that OCP toxicity in SH-SY5Y cells was mediated through pathways associated with the pathogenesis of neurodegenerative diseases. In conclusion, this study provides a basis for elucidating the molecular mechanisms of pesticide-induced neurotoxicity. Moreover, it introduced SH-SY5Y cells as a relevant in vitro model for investigating the neurotoxicity of pesticides in humans.

Efficacy and safety of a hyperoxygenated fatty acid compound in improving the microcirculation of purpura fulminans in paediatric patients with sepsis: a pilot study.

INTRODUCTION: Purpura fulminans (PF) is a serious complication of sepsis resulting from a set of alterations characterised by the development of ecchymotic haemorrhagic lesions and skin necrosis. AIM: To analyse the efficacy and safety of the topical application of HOFA compound, in the cutaneous microcirculation of PF lesions in paediatric patients affected by sepsis. MATERIAL AND METHODS: A prospective quasi-experimental pre-test/post-test single-group conducted in a Paediatric Intensive Care Unit of a third level hospital was performed. Paediatric patients aged 0-18 years with sepsis were included. Somatic oximetry values were measured before and after application of HOFAs every 4h over the first three days of the patients' hospitalisation. Patient's socio-demographic and clinical variables and somatic oximetry by placing a sensor for measuring tissue perfusion on the area with PF were determined. RESULTS: Four patients were recruited, with a median age of 98 months. The purpuric lesions measured were mainly located on both feet and hands and, in two patients, also on the lateral malleoli and calves of both lower extremities. A total of 225 measurements were obtained, with mean pre-intervention scores of 71.17±15.65% versus 73.68±14.83% post-intervention. Statistical significance (p<0.001) was observed upon comparison of the pre- and post-intervention measurements. CONCLUSIONS: Early and continued application of HOFAs in the management of sepsis-induced PF is an effective and safe practice in the cases analysed. In more than half of the episodes analysed, an increase in tissue microcirculation was observed after the application of HOFAs, with no adverse events.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Oncologic outcomes obtained after laparoscopic, robotic and/or single port nephroureterectomy for upper urinary tract tumours.

INTRODUCTION: Open surgery (ONU) is still considered to be the gold standard approach for nephroureterectomy (NU); however, with the introduction of laparoscopic surgery, minimally invasive techniques have been applied to surgical therapy of upper urinary tract tumours (UUT-UC) and they are gaining adepts. However, several concerns still exist about the safety of laparoscopic nephroureterectomy (LNU) in the treatment of UUT-UC, and different authors suggest that, although it could be equivalent to open surgery, this equivalence is not accomplished in all UUT-UC, suggesting that more advanced disease should undergo open surgery. More controversial still is the application of robotic surgery (RALNU) or really novel minimally invasive techniques, such as laparoendoscopic single-site surgery (LESSNU), for the treatment of UUT-UC. Although all these techniques seem feasible, their influence on oncologic results is still a matter of concern. METHODOLOGY: We present a review on the oncologic outcomes of minimally invasive laparoscopic techniques in the treatment of UUT-UC. We focus our analysis on oncologic outcomes and we also analyze the different techniques proposed for the treatment of the distal ureter during minimally invasive surgery for UUT-UC. In the absence of prospective randomized studies with large patient samples, we must base our conclusions on retrospective studies and longer follow-up. CONCLUSION: Given the evidence accumulated so far, LNU has proven to be equivalent or non-inferior, in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS) to ONU. Nevertheless, comparative studies are needed with longer follow-up before determining the equivalence of LNU in advanced tumours.

Cannabis derivatives therapy for a seronegative stiff-person syndrome: a case report.

WHAT IS KNOWN AND OBJECTIVE: Stiff-person syndrome (SPS) is an uncommon and disabling disorder characterized by progressive rigidity and episodic painful spasms involving axial and limb musculature. SPS treatment is mostly based on benzodiazepines, baclofen, immunosuppressants and intravenous immunoglobulin. Cannabis derivatives [tetrahydrocannabinol (THC) and cannabidiol (CBD)] are available as an oromucosal spray (Sativex(®)), indicated as add-on treatment, for symptom improvement in patients with moderate to severe spasticity because of multiple sclerosis (MS). Our objective is to report a case of seronegative SPS successfully treated with THC-CBD oromucosal spray. CASE SUMMARY: We report a case of a 40-year-old man presenting with progressive muscle stiffness and intermittent spasms for 6-years. The diagnosis of stiff-person syndrome was based on the clinical features and neuroelectrophysiologic findings of continuous motor unit activity. Glutamic acid decarboxylase autoantibodies was absent in our patient, in both serum and cerebrospinal fluid (CSF). Cannabis derivatives oromucosal spray was introduced after a series of unsatisfactory traditional medical treatments. After 14 months treated with THC-CBD oromucosal spray, improvement was verified in the eight dimensions of the scale of SF-36 quality of life questionnaire. WHAT IS NEW AND CONCLUSION: Clinical experience with cannabis derivatives in patients with multiple sclerosis is accumulating steadily, but there is no current literature about its efficacy for SPS. Because MS and SPS share some neurological symptoms such as spasticity and rigidity, it is thought that THC-CBC can be an option for SPS patient. Our case report suggests that THC-CBD oromucosal spray is an alternative treatment for patients with refractory SPS, and further validation is appropriate.

Multicenter study. Nursing professionals' perception of training needs in pain assessment in pediatric patients with cognitive dysfunction.

INTRODUCTION: Pediatric patients with cognitive dysfunction are at greater risk of pain than typically developing children. Pain assessment in these patients is complex and could generate uncertainty in health professionals about what the key aspects are. AIM: To determine the training needs perceived by nursing professionals regarding acute pain assessment in pediatric patients with cognitive dysfunction. METHODS: A descriptive, cross-sectional, and multicenter study was performed using a survey addressed to nursing professionals who work in pediatrics during the months of August and September 2022. RESULTS: 163 responses were obtained. Most of the professionals who responded were female (92.6%, n = 151), with a mean age of 38.98 ±â€¯10.40 years. The most frequent work unit was the pediatric intensive care unit (PICU), in 36% (n = 58). Most of the participants reported not having previously received training on pain assessment in pediatric patients with cognitive disabilities (85.9%, n = 139). However, 70.4% (n = 114) considered it "very necessary" for the development of their work to receive specific training on this topic. Knowing how to assess acute pain in this population (85.3%, n = 139) and knowing the clinical and behavioral manifestations of pain in this type of patient (84.7%, n = 138) were the aspects that obtained higher scores. CONCLUSION: This research notes more than 90% of participants consider "quite necessary" and "strong necessary" to be training in pediatric cognitive dysfunction patients pain assessment. Furthermore, work experience, academic education and to be pediatric specialist obtain statistical significance data.

[Persistent supraventricular tachycardia after volatile inhalational anaesthetic induction with sevoflurane in a pediatric patient].

Inhaled anaesthetic induction with sevoflurane is very common in the pediatric population. Sevoflurane systemic effects are widely known, while not all the side effects are known. We present a four year-old child who developed a persistent supraventricular tachycardia after inhaled anaesthetic induction with sevoflurane. The arrhythmia did not end until sevoflurane was stopped and changed to an intravenous continuous perfusion of hypnotic drugs (propofol and remiphentanyl). The exact mechanism for such a causal relationship with sevoflurane administration is unknown, and possible diagnoses include atrioventricular nodal reentry tachycardia (AVNRT) and the existence of an accessory pathway. An episode of persistent supraventricular tachycardia with a clear causal relationship with sevoflurane administration is not found in the literature.

Efficacy of a theoretical and practical programme to newly hired nursing personnel in a Paediatric Intensive Care Unit: A pilot study.

AIMS: (1) to design a training programme for newly hired nursing personnel and (2) to determine self-perception and perceived stress before and after the theoretical and practical parts of the programme with high fidelity simulation activities. METHODS: A pilot quasi-experimental pretest-posttest study without control group conducted in a Paediatric Intensive Care Unit from October 2018 to April 2019 was conducted. A newly hired nursing personnel training programme was first designed and delivered. Later, the participants' self-perception was assessed, as well as their perceived stress and grade of satisfaction using two different Likert scales. RESULTS: A total of 20 newly hired nurses participated in the study, 90% (n = 18) were female with a median age of 25.5 ± 4.53 years. Higher scores were obtained in participants' self-perception before and after the theoretical training. Lower significant median scores of the participants' stress perception were found (6.9 ± 1.57 versus 5.6 ± 1.794). In the practical part of the programme, we obtained higher scores in all items, as well as lower median scores in stress perception (6.4 ± 1.73 versus 5.6 ± 1.93). CONCLUSIONS: A theoretical and practical programme for newly hired nursing personnel in a Paediatric Intensive Care Unit improved participants' self-perception and reduced their perceived median scores in stress levels.

Immune surveillance for six vaccinable pathogens using paired plasma and dried blood spots in HIV infected and uninfected children in Kinshasa.

Child vaccination reduces infant mortality rates. HIV-infected children present higher risk of diseases than non-infected. We report the protection coverage rates for 6 vaccine-preventable diseases in a paediatric population from the Democratic Republic of the Congo (DRC) and the impact of HIV infection, providing the first data on the validity of dried blood samples (DBS) to monitor the immune protection. During 2016-2018 DBS from 143 children/adolescents were collected in Kinshasa (DRC), being 52 HIV-infected. Forty-two had a paired plasma sample. Protective IgG was quantified (VirClia-IgG,VIRCELL) to obtain the optimal cut-off in IgG detection in DBS. ROC curves were generated with R software and statistical analyses with Stata. Protective IgG levels varied across pathogens, not reaching herd immunity. HIV-infected presented lower vaccine protection than uninfected for all analyzed pathogens, except rubella, with statistically significant differences for measles (30.8% vs. 53.8%; p = 0.008) and tetanus (3.8% vs. 22%; p = 0.0034). New cut-offs were calculated when using DBS to improve test performance. We reinforce the necessity to increase pediatric vaccination coverage in Kinshasa, especially in HIV seropositive, with less capacity to maintain adequate antibody levels. DBS were useful to monitor vaccination coverage in seroprevalence studies in resource-limited settings, after optimizing the cut-off value for each pathogen.

Specificity and sensibility of the Spanish version of the COMFORT Behaviour Scale for assessing pain, grade of sedation and withdrawal syndrome in the critically ill paediatric patient. Multicentre COSAIP study (Phase 1).

AIM: The main aim of this investigation was to analyse the specificity and sensibility of the COMFORT Behaviour Scale (CBS-S) in assessing grade of pain, sedation, and withdrawal syndrome in paediatric critical care patients. METHOD: An observational, analytical, cross-sectional and multicentre study conducted in Level III Intensive Care Areas of 5 children's university hospitals. Grade of sedation was assessed using the Spanish version of the CBS-S and the Bispectral Index on sedation, once per shift over one day. Grade of withdrawal was determined using the CBS-S and the Withdrawal Assessment Tool-1, once per shift over three days. RESULTS: A total of 261 critically ill paediatric patients with a median age of 5.07 years (P25:0.9-P75:11.7) were included in this study. In terms of the predictive capacity of the CBS-S, it obtained a Receiver Operation Curve of .84 (sensitivity of 81% and specificity of 76%) in relation to pain; .62 (sensitivity of 21% and specificity of 78%) in relation to sedation grade, and .73% (sensitivity of 40% and specificity of 74%) in determining withdrawal syndrome. CONCLUSIONS: The Spanish version of the COMFORT Behaviour Scale could be a useful, sensible and easy scale to assess the degree of pain, sedation and pharmacological withdrawal of critically ill paediatric patients.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naive Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57).

BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. METHODS: Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL) ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin). RESULTS: Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/µL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. CONCLUSIONS: We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.