Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a single-center experience with 63 patients.

BACKGROUND: Intravenous immunoglobulin (IVIG) is prepared using purified human plasma. IVIG therapy has immunomodulatory effects on autoimmune diseases, including severe systemic lupus erythematosus (SLE). However, reports of its effects on large cohorts are scarce. METHODS: This single-center retrospective study included SLE patients treated with at least one IVIG cycle for SLE complications. Demographic data, indications, cycle numbers, and clinical improvement with IVIG were evaluated. SLE Disease Activity Index 2000 (SLEDAI-2K) scores were calculated at admission and after IVIG treatment in order to measure clinical improvement. RESULTS: Sixty-three SLE patients treated with IVIG (median age: 29 years; interquartile range 21-36 years; 84.13% female) were included, who received 2 g/kg IVIG for two to five days. Main indications were immune thrombocytopenia, hypogammaglobulinemia, infection during a SLE flare, bicytopenia, and immune hemolytic anemia. Seven patients received more than one IVIG cycle without severe adverse effects. Significant differences were found in SLEDAI-2K scores when the indications were immune thrombocytopenia and hypogammaglobulinemia, with a trend for hemolytic anemia. Patients with concomitant infection, myopathy, and gastrointestinal involvement showed a considerable reduction in their last SLEDAI-2K scores. Fourteen patients died during hospitalization, mainly due to septic shock and active SLE. CONCLUSIONS: IVIG showed adequate tolerance and effectiveness in selected severe SLE manifestations, mainly hematological involvement. It was useful for concomitant infection.

Effectiveness and predictors of failure of noninvasive mechanical ventilation in acute respiratory failure.

OBJECTIVE: To assess the effectiveness and identify predictors of failure of noninvasive ventilation. DESIGN: A retrospective, longitudinal descriptive study was made. SETTING: Adult patients with acute respiratory failure. PATIENTS: A total of 410 consecutive patients with noninvasive ventilation treated in an Intensive Care Unit of a tertiary university hospital from 2006 to 2011. PROCEDURES: Noninvasive ventilation. MAIN VARIABLES OF INTEREST: Demographic variables and clinical and laboratory test parameters at the start and two hours after the start of noninvasive ventilation. Evolution during admission to the Unit and until hospital discharge. RESULTS: The failure rate was 50%, with an overall mortality rate of 33%. A total of 156 patients had hypoxemic respiratory failure, 87 postextubation respiratory failure, 78 exacerbation of chronic obstructive pulmonary disease, 61 hypercapnic respiratory failure without chronic obstructive pulmonary disease, and 28 had acute pulmonary edema. The failure rates were 74%, 54%, 27%, 31% and 21%, respectively. The etiology of respiratory failure, serum bilirubin at the start, APACHEII score, radiological findings, the need for sedation to tolerate noninvasive ventilation, changes in level of consciousness, PaO2/FIO2 ratio, respiratory rate and heart rate from the start and two hours after the start of noninvasive ventilation were independently associated to failure. CONCLUSIONS: The effectiveness of noninvasive ventilation varies according to the etiology of respiratory failure. Its use in hypoxemic respiratory failure and postextubation respiratory failure should be assessed individually. Predictors of failure could be useful to prevent delayed intubation.

Epidemiology of severe trauma in Spain. Registry of trauma in the ICU (RETRAUCI). Pilot phase. / Epidemiología del trauma grave en España. REgistro de TRAuma en UCI (RETRAUCI). Fase piloto.

OBJECTIVE: To describe the characteristics and management of severe trauma disease in Spanish Intensive Care Units (ICUs). Registry of trauma in the ICU (RETRAUCI). Pilot phase. DESIGN: A prospective, multicenter registry. SETTING: Thirteen Spanish ICUs. PATIENTS: Patients with trauma disease admitted to the ICU. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiology, out-of-hospital attention, registry of injuries, resources utilization, complications and outcome were evaluated. RESULTS: Patients, n=2242. Mean age 47.1±19.02 years. Males 79%. Blunt trauma 93.9%. Injury Severity Score 22.2±12.1, Revised Trauma Score 6.7±1.6. Non-intentional in 84.4% of the cases. The most common causes of trauma were traffic accidents followed by pedestrian and high-energy falls. Up to 12.4% were taking antiplatelet medication or anticoagulants. Almost 28% had a suspected or confirmed toxic influence in trauma. Up to 31.5% required an out-of-hospital artificial airway. The time from trauma to ICU admission was 4.7±5.3hours. At ICU admission, 68.5% were hemodynamically stable. Brain and chest injuries predominated. A large number of complications were documented. Mechanical ventilation was used in 69.5% of the patients (mean 8.2±9.9 days), of which 24.9% finally required a tracheostomy. The median duration of stay in the ICU and in hospital was 5 (range 3-13) and 9 (5-19) days, respectively. The ICU mortality rate was 12.3%, while the in-hospital mortality rate was 16.0%. CONCLUSIONS: The pilot phase of the RETRAUCI offers a first impression of the epidemiology and management of trauma disease in Spanish ICUs.

Mortality prediction using TRISS methodology in the Spanish ICU Trauma Registry (RETRAUCI).

OBJECTIVES: To validate Trauma and Injury Severity Score (TRISS) methodology as an auditing tool in the Spanish ICU Trauma Registry (RETRAUCI). DESIGN: A prospective, multicenter registry evaluation was carried out. SETTING: Thirteen Spanish Intensive Care Units (ICUs). PATIENTS: Individuals with traumatic disease and available data admitted to the participating ICUs. INTERVENTIONS: Predicted mortality using TRISS methodology was compared with that observed in the pilot phase of the RETRAUCI from November 2012 to January 2015. Discrimination was evaluated using receiver operating characteristic (ROC) curves and the corresponding areas under the curves (AUCs) (95% CI), with calibration using the Hosmer-Lemeshow (HL) goodness-of-fit test. A value of p<0.05 was considered significant. MAIN VARIABLES OF INTEREST: Predicted and observed mortality. RESULTS: A total of 1405 patients were analyzed. The observed mortality rate was 18% (253 patients), while the predicted mortality rate was 16.9%. The area under the ROC curve was 0.889 (95% CI: 0.867-0.911). Patients with blunt trauma (n=1305) had an area under the ROC curve of 0.887 (95% CI: 0.864-0.910), and those with penetrating trauma (n=100) presented an area under the curve of 0.919 (95% CI: 0.859-0.979). In the global sample, the HL test yielded a value of 25.38 (p=0.001): 27.35 (p<0.0001) in blunt trauma and 5.91 (p=0.658) in penetrating trauma. TRISS methodology underestimated mortality in patients with low predicted mortality and overestimated mortality in patients with high predicted mortality. CONCLUSIONS: TRISS methodology in the evaluation of severe trauma in Spanish ICUs showed good discrimination, with inadequate calibration - particularly in blunt trauma.

Prognostic factors associated with mortality in patients with severe trauma: from prehospital care to the Intensive Care Unit.

OBJECTIVE: To identify factors related to mortality in adult trauma patients, analyzing the clinical, epidemiological and therapeutic characteristics at the pre-hospital levels, in the Emergency Care Department and in Intensive Care. DESIGN: A retrospective, longitudinal descriptive study was carried out. Statistical analysis was performed using SPSS, MultBiplot and data mining methodology. SETTING: Adult multiple trauma patients admitted to the Salamanca Hospital Complex (Spain) from 2006 to 2011. MAIN VARIABLES OF INTEREST: Demographic variables, clinical, therapeutic and analytical data from the injury site to ICU admission. Evolution from ICU admission to hospital discharge. RESULTS: A total of 497 patients with a median age of 45.5 years were included. Males predominated (76.7%). The main causes of injury were traffic accidents (56.1%), precipitation (18.4%) and falls (11%). The factors with the strongest association to increased mortality risk (P<.05) were age > 65 years (OR 3.15), head injuries (OR 3.1), pupillary abnormalities (OR 113.88), level of consciousness according to the Glasgow Coma Scale ≤ 8 (OR 12.97), and serum lactate levels > 4 mmol/L (OR 9.7). CONCLUSIONS: The main risk factors identified in relation to the prognosis of trauma patients are referred to the presence of head injuries. Less widely known statistical techniques such as data mining or MultBiplot also underscore the importance of other factors such as lactate concentration. Trauma registries help assess the healthcare provided, with a view to adopting measures for improvement.

[Prognostic factors in severe traumatic brain injury]. / Factores pronósticos del traumatismo craneoencefálico grave.

OBJECTIVE: To describe the factors associated to mortality of patients with severe traumatic brain injury (TBI). DESIGN: A retrospective observational study was made of patients with severe TBI covering the period between 1 January 2007 and 31 December 2010. SETTING: Virgen de la Vega Hospital, Salamanca (Spain). PATIENTS: All patients hospitalized during the consecutive study period. MAIN VARIABLES OF INTEREST: The dependent variable has been the death rate, while the independent variables were divided into two groups: epidemiological and clinical. RESULTS: The mean patient age was the 50.84 years; 75.5% were males. The average score on the Glasgow Coma Scale (GCS) was 5.09, and the average Injury Severity Score (ISS) was 30.8. Higher mortality was observed in older patients with a higher ISS score. A total of 68.1% of the patients in which intracranial pressure (ICP) was monitored showed intracranial hypertension (ICH). The mortality rate in patients with severe TBI was 36.8%, and was associated mainly to a lower GCS score, the existence of hyperglycemia, coagulopathy, hypoxemia, the presence of mydriasis and shock. The independent mortality indicators in patients with severe TBI were the existence of mydriasis (OR: 32.75), the GCS score (OR: 2.65) and hyperglycemia (OR: 6.08). CONCLUSIONS: The existence of mydriasis, the GCS score and hyperglycemia should be taken into account as prognostic factors in TBI patients.

Flu and pertussis vaccination during pregnancy in Geneva during the COVID-19 pandemic: A multicentric, prospective, survey-based study.

OBJECTIVE: To determine pertussis and influenza vaccination coverage during pregnancy among women delivering in all the maternities of Geneva (Switzerland), during the COVID-19 pandemic. METHODS: All women delivering in all the maternity centres of the canton of Geneva from 1st November 2020 to 30th November 2020 (beginning of the flu vaccination season) and from 8th March 2021 to 7th April 2021 (end of the flu vaccination season) had their records checked upon admission to the labour ward regarding pertussis and influenza vaccination during pregnancy. Reasons for non-vaccination were recorded. Univariate and multivariate analyses were done to identify predictors of vaccine uptake. RESULTS: 951 women delivered in Geneva during the two study periods, of which 950 were included in the study. 86.2% were vaccinated against pertussis, with no significant difference between the study periods (87.5% vs 85% at the beginning and end of the flu vaccination season respectively). 49.8% were vaccinated against influenza, with no significant difference between the study periods (48.8% vs 50.7% beginning and end of the flu vaccination season respectively). The influenza vaccine was 5 times more likely not to be proposed (8.9% vs. 1.7%) and 3 times more likely to be refused (26.6% vs. 8%) than the pertussis vaccine. Main reason for refusal was a lack of maternal desire for both vaccines, but not vaccine fear. Maternal parity ≥ 1 was significantly associated with pertussis vaccine uptake at univariate analysis. Women were significantly more likely to accept the influenza vaccine if they had a university degree or if they did not deliver in a midwife-only run delivery unit in both univariate and multivariate analysis. CONCLUSIONS: In Geneva, most gynaecologists offer pertussis immunization during antenatal care and uptake is high, but more efforts must be done to increase influenza vaccination coverage. Education level impacts maternal flu vaccination uptake, but other social disparities did not.

Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Assessment of mycobacteremia detection as a complementary method for the diagnosis of tuberculosis in HIV-infected patients.

The purpose of this investigation was to assess the usefulness of mycobacteremia detection in human immunodeficiency virus (HIV) patients with suspected tuberculosis. The study included 47 patients with suspected tuberculosis and confirmed HIV infection. A first blood sample was incubated in a BACTEC 9050 MB system, while white blood cells isolation was performed on a second blood specimen before incubation in a BACTEC MGIT 960 system. The third specimen was taken from the affected organs of each patient according to their clinical profile. Twelve (25.5%) patients were positive for mycobacterial infection identified by any of the methods used. Ten (21.2%) were positive for Mycobacterium tuberculosis and 2 (4.3%) for M. avium. Six patients were diagnosed by the culture of specimen from affected organs only, whilst three other patients were positive exclusively for blood cultures. Three additional patients were diagnosed by both methods. Four patients with negative cultures were ultimately diagnosed with tuberculosis by measuring the adenosine deaminase levels. Mycobacteremia detection can be used to increase the sensitivity of the diagnosis of tuberculosis and other mycobacteria in patients with HIV. However, it cannot be used as the sole diagnostic method. Clinical specimen cultures do not provide 100% diagnostic accuracy and it is, therefore, critical to further improve the mycobacteria detection sensitivity.

An unusual case of posterior elbow dislocation with proximal radioulnar translocation. / Un caso inusual de luxación posterior del codo con translocación radiocubital proximal.

We present a 9-year-old girl who suffered a posterior dislocation of the right elbow with a proximal translocation between the ulna and the radius. It is a type of exceptional dislocation which in our case was not accompanied by lesions of the joint surfaces of the elbow unlike most cases already published. This article stresses the importance of making an early diagnosis of this variety of dislocation; this is the best way to prevent it from going unnoticed. The use of Computed Tomography (CT) helped this early diagnosis, enabling an immediate closed orthopaedic reduction and achieving a cure without sequelae.

Toxin-antitoxin systems shows variability among Mycobacterium tuberculosis lineages.

The toxin-antitoxin (TA) systems are operons involved in the formation of persistent cells and in stress situations in microorganism. TA systems are widely distributed in Mycobacterium tuberculosis (MTB). The objective of this study was to determine the distribution and variability of protein sequences of TA systems in seven MTB lineages. Protein prediction on 73 genomes of different lineage was made using Prodigal, and profile hidden Markov models (PHMMs) of 225 reference TA proteins were constructed with HMMER. An homology search was made comparing the predicted proteins to PHMMs. Consecutive proteins that matched PHMMs (forming an operon) were selected. Thereafter, clustering of orthologous genes was made for further mutation scanning through multiple alignments. All proteins found belong to TA types II and IV, and 45 proteins were found completely conserved. Six uncharacterized antitoxins homologous to VapB11, VapB5, VapB45, VapB13, ParD1 and RelB were found. Multiple alignments revealed differences among lineages with specific mutations suitable for genotyping. Significant changes in amino acid sequences caused by frameshift mutations were found in 46 TA proteins.

Liver damage in bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis is an emerging disease with a poor prognosis and high mortality rate that is even surpassing some types of cancer. This disease has been linked to the concomitant appearance of liver cirrhosis. Bleomycin-induced pulmonary fibrosis is a widely used mouse model that mimics the histopathological and biochemical features of human systemic sclerosis, an autoimmune disease that is associated with inflammation and expressed in several corporal systems as fibrosis or other alterations. To determine the effects on proliferation, redox and inflammation protein expression markers were analyzed by immunohistochemistry. Analyses showed a significant increase in protein oxidation levels by lipoperoxidation bio-products and in proliferation and inflammation processes. These phenomena were associated with the induction of the redox status in mice subjected to 100 U/kg bleomycin. These findings clearly show that the bleomycin model induces histopathological alterations in the liver and partially reproduces the complexity of systemic sclerosis. Our results using the bleomycin-induced pulmonary fibrosis model provide a protocol to investigate the mechanism underlying the molecular alteration found in the liver linked to systemic sclerosis.

Rapid detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis by the direct thin-layer agar method.

We evaluated thin-layer agar (TLA) for the detection of resistance of Mycobacterium tuberculosis to rifampicin (RMP) and isoniazid (INH) as a direct method in patients at risk of multidrug-resistant tuberculosis (MDR-TB). Quadrant TLA plates contain 7H10 Middlebrook growth control, para-nitrobenzoic acid, INH and RMP. Detection of RMP and INH resistance by TLA was compared to that in indirect conventional drug susceptibility testing (DST) and conventional culture media. Median time for growth was respectively 22, 10 and 7.6 days for Löwenstein-Jensen, TLA and the Mycobacterial Growth Indicator Tube. TLA sensitivity, specificity and predictive values for RMP and INH resistance were 100%. Time to resistance detection was respectively 11 and 11.5 days for RMP and INH. TLA showed a rapid turnaround time and performance comparable to conventional DST methods.

Scoring severity in trauma: comparison of prehospital scoring systems in trauma ICU patients.

PURPOSE: We evaluated the predictive ability of mechanism, Glasgow coma scale, age and arterial pressure (MGAP), Glasgow coma scale, age and systolic blood pressure (GAP), and triage-revised trauma Score (T-RTS) scores in patients from the Spanish trauma ICU registry using the trauma and injury severity score (TRISS) as a reference standard. METHODS: Patients admitted for traumatic disease in the participating ICU were included. Quantitative data were reported as median [interquartile range (IQR), categorical data as number (percentage)]. Comparisons between groups with quantitative variables and categorical variables were performed using Student's T Test and Chi Square Test, respectively. We performed receiving operating curves (ROC) and evaluated the area under the curve (AUC) with its 95 % confidence interval (CI). Sensitivity, specificity, positive predictive and negative predictive values and accuracy were evaluated in all the scores. A value of p < 0.05 was considered significant. RESULTS: The final sample included 1361 trauma ICU patients. Median age was 45 (30-61) years. 1092 patients (80.3 %) were male. Median ISS was 18 (13-26) and median T-RTS was 11 (10-12). Median GAP was 20 (15-22) and median MGAP 24 (20-27). Observed mortality was 17.7 % whilst predicted mortality using TRISS was 16.9 %. The AUC in the scores evaluated was: TRISS 0.897 (95 % CI 0.876-0.918), MGAP 0.860 (95 % CI 0.835-0.886), GAP 0.849 (95 % CI 0.823-0.876) and T-RTS 0.796 (95 % CI 0.762-0.830). CONCLUSIONS: Both MGAP and GAP scores performed better than the T-RTS in the prediction of hospital mortality in Spanish trauma ICU patients. Since these are easy-to-perform scores, they should be incorporated in clinical practice as a triaging tool.

Evaluation of a rapid culture method for tuberculosis diagnosis: a Latin American multi-center study.

SETTINGS: Tuberculosis (TB) diagnostic laboratories in Latin America. OBJECTIVES: Evaluation of thin-layer agar (TLA) compared to Löwenstein-Jensen (LJ) culture for the diagnosis of TB. DESIGN: Phase II prospective study in six laboratories. Samples included sputum and extra-pulmonary specimens from patients with a clinical diagnosis of TB. Respiratory samples were decontaminated using NaOH/ NALC; all samples were centrifuged, stained with Ziehl-Neelsen for acid-fast bacilli (AFB), cultured on LJ and TLA and identified according to recommended procedures. Sensitivity and likelihood ratios (LR), growth detection time and contamination rate were calculated for both media. RESULTS: A total of 1118 clinical specimens were studied. Cultures detected Mycobacterium tuberculosis in all AFB-positive samples, whereas for AFB-negative specimens LJ detected 3.2% and TLA 4.4%. Sensitivity was 92.6% (95%CI 87.9-95.9) and 84.7% (95%CI 78.8-89.0) for TLA and LJ, respectively. Positive and negative LRs were similar. Contamination was 5.1% for TLA and 3.0% for LJ. Median time to detection of a positive culture was 11.5 days (95%CI 9.3-15.0) for TLA and 30.5 days (95%CI 26.9-39.0) for LJ (P < 0.0001). CONCLUSION: Difference in the characteristics of the participating laboratories, the disease prevalence and the number and type of specimens processed did not affect the overall performance of TLA as compared to LJ, supporting the robustness of the method and its feasibility in different laboratory settings.

[Three successive fractures of different hip femoral stems on the same patient]. / Tres roturas sucesivas de los vástagos protésicos de cadera implantados en una paciente.

The clinical case of an 80-year-old female who suffered three fractures in uncemented stems implanted in her right hip in a period of three years is presented. A fracture occurred in the prosthetic neck and the other two at the juncture of the conical and cylindrical stem portion, coinciding with the metaphyseal-diaphyseal junction of the femur. The main causes of the failure were an increasing concentration of forces at the level of the implant as a consequence of the increased length of the neck and lateralization of the femur (offset). Other causes that have contributed to this prosthetic failure are analyzed.

Se presenta el caso clínico de una paciente de 80 años que sufrió tres roturas de vástagos protésicos no cementados implantados en su cadera derecha en un período de tres años. Una rotura ocurrió en el cuello protésico y las otras dos en la unión de la porción cónica y cilíndrica del vástago, coincidiendo con la zona metafiso-diafisaria del fémur. La causas principales del fallo han sido un incremento de la concentración de fuerzas a nivel del implante como consecuencia del aumento de la longitud del cuello y de la lateralización femoral (offset). Se analizan otras causas que han podido contribuir a dicho fallo protésico.

Whole-Genome Sequencing of Two Latin American-Mediterranean Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates from Medellín, Colombia.

Colombia, with a tuberculosis incidence of 33 cases per 100,000 population, is one of the countries that have reported extensively drug-resistant Mycobacterium tuberculosis (XDR-TB). We report the high-quality draft genome sequences of two Latin American-Mediterranean XDR-TB clinical isolates (TBR-152 and TBR-175), comprising 4,303,775 bp and 4,330,115 bp, respectively.

Draft Genome Sequence of a Mycobacterium africanum Clinical Isolate from Antioquia, Colombia.

Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex. Most commonly found in West African countries, it has scarcely been described in South America. Here, we report the first genome sequence of a Colombian M. africanum clinical isolate. It is composed of 4,493,502 bp, with 4,069 genes.