Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Characterization of Novel Pathogenic Variants Leading to Caspase-8 Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome.

Pathogenic RIPK1 variants have been described as the cause of two different inborn errors of immunity. Biallelic loss-of-function variants cause the recessively inherited RIPK1 deficiency, while monoallelic variants impairing the caspase-8-mediated RIPK1 cleavage provoke a novel autoinflammatory disease (AID) called cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. The aim of this study was to characterize the pathogenicity of two novel RIPK1 variants located at the cleavage site of caspase-8 detected in patients with dominantly-inherited, early-onset undefined AID. RIPK1 genotyping was performed by Sanger and next-generation sequencing. Clinical and analytical data were collected from medical charts, and in silico and in vitro assays were performed to evaluate the functional consequences. Genetic analyses identified two novel heterozygous RIPK1 variants at the caspase-8 cleavage site (p.Leu321Arg and p.Asp324Gly), which displayed a perfect intrafamilial phenotype-genotype segregation following a dominant inheritance pattern. Structural analyses suggested that these variants disrupt the normal RIPK1 structure, probably making it less accessible to and/or less cleavable by caspase-8. In vitro experiments confirmed that the p.Leu321Arg and p.Asp324Gly RIPK1 variants were resistant to caspase-8-mediated cleavage and induced a constitutive activation of necroptotic pathway in a similar manner that previously characterized RIPK1 variants causing CRIA syndrome. All these results strongly supported the pathogenicity of the two novel RIPK1 variants and the diagnosis of CRIA syndrome in all enrolled patients. Moreover, the evidences here collected expand the phenotypic and genetic diversity of this recently described AID, and provide interesting data about effectiveness of treatments that may benefit future patients.

Novel evidences of atypical manifestations in cryopyrin-associated periodic syndromes.

OBJECTIVES: Cryopyrin-associated periodic syndromes (CAPS) usually start during infancy as an urticarial-like rash and a marked acute phase response, with additional manifestations appearing during its evolution. The aim of this study was to expand the clinical diversity of CAPS by the description of novel atypical features. METHODS: Clinical data were collected from patients' medical charts. Sanger sequencing analyzed NLRP3. Response to anti-IL-1 blockade was evaluated by clinical assessments and by measurements of laboratory parameters. RESULTS: Seventeen patients from two families (A and B), carrying the p.Ala439Thr and p.Arg260Trp NLRP3 mutations respectively, were enrolled. The disease was unexpectedly atypical in all members of Family A, with a 16-year-old asymptomatic carrier, and onset in adulthood associated with absence of skin lesions in four affected members. Surprisingly, one patient from each family suffered from severe haemorrhagic cystitis due to AA amyloidosis in the urinary bladder. Members of Family B displayed a classical phenotype, with two patients suffering from olfactive disorders. CONCLUSIONS: Our evidence suggests that CAPS may occasionally be presented as a late-onset, recurrent inflammatory disease without urticarial-like rash. In some patients, AA amyloidosis in strange locations like urinary bladder may complicate the clinical course. The response to IL-1 blockade in these atypical CAPS was similar to that described in classical forms. Consequently, we suggest that CAPS should be included in the differential diagnosis of adult patients with unexplained, recurrent inflammatory diseases, and once confirmed, the early initiation of anti-IL-1 blockade will probably prevent the development of life-threatening complications.

The obesity paradox in stroke: impact on mortality and short-term readmission.

BACKGROUND: The aim of the present study was to assess the association of obesity with the mortality of hospitalized patients with acute stroke and the risk of readmission in less than 30 days. METHODS: A retrospective chart review of a cohort of consecutive patients admitted with stroke as the primary reason for discharge in Spain between January 1, 2005, and December 31, 2011, was performed. Patients with a diagnosis of obesity were identified. The mortality and readmittance indexes of obese patients were compared against the subpopulation without theses diagnosis. RESULTS: A total of 201,272 stroke admittances were analyzed, and 14,047 (7.0%) diagnosis of obesity were identified. In-hospital global mortality reached 14.9%, and readmittance risk was 5.9%. Obese patients showed a lower in-hospital mortality risk (odds ratio [OR], .71; 95% confidence interval [CI], .67-.76) and early readmittance risk (OR, .89; 95% CI, .82-.96) than the nonobese even after adjusting for possible confounding factors. CONCLUSIONS: Obesity in those hospitalized for stroke is associated with reduced in-hospital mortality risk and early readmittance.

Frequency of hypoglycemia and its impact on length of stay, mortality, and short-term readmission in patients with diabetes hospitalized in internal medicine wards.

OBJECTIVE: To evaluate whether hypoglycemia is associated with increases in length of stay (LOS), inpatient mortality, and readmission among patients with diabetes hospitalized in internal medicine wards. METHODS: A retrospective cohort study was carried out using the Basic Minimum Data Set registry of the Spanish National Health System, which contains clinical and administrative information for every patient discharged from system hospitals. The analysis included patients discharged between January 2005 and December 2010 and had a primary (i.e., reason for the admission) or secondary diagnosis of diabetes and a secondary diagnosis of hypoglycemia. The associations between hypoglycemia and the study outcomes (mortality, readmission, and LOS) were evaluated using multivariate and multilinear regression models that included age, sex, and the Charlson index as covariates. RESULTS: During the study period, 3,361,104 patients were admitted to internal medicine wards in the National Health System. Of these, 921,306 (27.4%) had diagnoses of diabetes, and among these patients, 46,408 (5%) had secondary hypoglycemia. A total of 4,754 (10.2%) patients with secondary hypoglycemia died during their hospital stays, compared with 83,508 (9.5%) patients without hypoglycemia. The multivariate/multilinear regression models demonstrated significant associations between the presence of secondary hypoglycemia and greater inpatient mortality (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.20-1.28), a greater likelihood of readmission (OR 1.20, 95% CI 1.17-1.23), and an increased LOS (ß 1.24, 95% CI 1.15-1.35). CONCLUSION: Hypoglycemia in patients with diabetes hospitalized in internal medicine wards is associated with increases in the LOS, inpatient mortality, and early readmission.

Case report: Novel compound heterozygous IL1RN mutations as the likely cause of a lethal form of deficiency of interleukin-1 receptor antagonist.

Undiagnosed monogenic diseases represent a challenging group of human conditions highly suspicious to have a genetic origin, but without conclusive evidences about it. We identified two brothers born prematurely from a non-consanguineous healthy couple, with a neonatal-onset, chronic disease characterized by severe skin and bone inflammatory manifestations and a fatal outcome in infancy. We conducted DNA and mRNA analyses in the patients' healthy relatives to identify the genetic cause of the patients' disease. DNA analyses were performed by both Sanger and next-generation sequencing, which identified two novel heterozygous IL1RN variants: the intronic c.318 + 2T>G variant in the father and a ≈2,600-bp intragenic deletion in the mother. IL1RN mRNA production was markedly decreased in both progenitors when compared with healthy subjects. The mRNA sequencing performed in each parent identified two novel, truncated IL1RN transcripts. Additional experiments revealed a perfect intrafamilial phenotype-genotype segregation following an autosomal recessive inheritance pattern. The evidences shown here supported for the presence of two novel loss-of-function (LoF) IL1RN pathogenic variants in the analyzed family. Biallelic LoF variants at the IL1RN gene cause the deficiency of interleukin-1 receptor antagonist (DIRA), a monogenic autoinflammatory disease with marked similarities with the patients described here. Despite the non-availability of the patients' samples representing the main limitation of this study, the collected evidences strongly suggest that the patients described here suffered from a lethal form of DIRA likely due to a compound heterozygous genotype at IL1RN, thus providing a reliable genetic diagnosis based on the integration of old medical information with currently obtained genetic data.

Hip fracture in hospitalized medical patients.

BACKGROUND: The aim of the present study is to analyze the incidence of hip fracture as a complication of admissions to internal medicine units in Spain. METHODS: We analyzed the clinical data of 2,134,363 adults who had been admitted to internal medicine wards. The main outcome was a diagnosis of hip fracture during hospitalization.Outcome measures included rates of in-hospital fractures, length of stay and cost. RESULTS: A total of 1127 (0.057%) admittances were coded with an in-hospital hip fracture. In hospital mortality rate was 27.9% vs 9.4%; p < 0.001, and the mean length of stay was significantly longer for patients with a hip fracture (20.7 days vs 9.8 days; p < 0.001). Cost were higher in hip-fracture patients (6927€ per hospitalization vs 3730€ in non fracture patients). Risk factors related to fracture were: increasing age by 10 years increments (OR 2.32 95% CI 2.11-2.56), female gender (OR 1.22 95% CI 1.08-1.37), admission from nursing home (OR 1.65 95% CI 1.27-2.12), dementia (1.55 OR 95% CI1.30-1.84), malnutrition (OR 2.50 95% CI 1.88-3.32), delirium (OR 1.57 95% CI 1.16-2.14), and anemia (OR 1.30 95%CI 1.12-1.49). CONCLUSIONS: In-hospital hip fracture notably increased mortality during hospitalization, doubling the mean length of stay and mean cost of admission. These are reasons enough to stress the importance of designing and applying multidisciplinary plans focused on reducing the incidence of hip fractures in hospitalized patients.

Venous thromboembolism in COPD hospitalized patients.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for venous thromboembolism (VTE). We analyzed a large Spanish database to determine the incidence of VTE in these patients during hospitalization. A retrospective chart review of cohort of consecutive patients admitted with COPD as the primary reason for discharge in Spain between January 1st 2006 and December 31st 2007 was performed. For each patient, demographic data, risk factors for VTE and the diagnosis of VTE during hospitalization was recorded. We analyzed the clinical data of 313,233 adults with acute exacerbations of COPD admitted to the hospital at any public centre in Spain, in 2006 and 2007. We identify 3,562 new diagnosed VTE events among 270,840 COPD patients hospitalized more than two days (incidence 1.32%). Hospitalized-acquired VTE risk factors were male gender (odds ratio [OR] 1.77; CI95% 1.66-1.90), neoplasic disease (OR 2.93 CI95% 2.69-3.16, systemic arterial disease (OR 1.17 CI95% 1.10-1.36), decubitus ulcer (OR 1.19 CI95% 1.01-1.43), diabetes (OR 0.74 IC95% 0.69-0.81), and atrial fibrillation (OR 0.79 CI95% 0.72-0.87). VTE appears as a major threat to patients admitted for acute exacerbation of COPD, and pharmacologic prophylaxis should be considered in all high risk situations.

First Description of Late-Onset Autoinflammatory Disease Due to Somatic NLRC4 Mosaicism.

OBJECTIVE: Autoinflammatory diseases are inherited disorders of innate immunity that usually start during childhood. However, several recent reports have described an increasing number of patients with autoinflammatory disease starting in adulthood. This study was undertaken to investigate the underlying cause of a case of late-onset uncharacterized autoinflammatory disease. METHODS: Genetics studies were performed using Sanger sequencing and next-generation sequencing (NGS) methods. In silico, in vitro, and ex vivo analyses were performed to determine the functional consequences of the detected variant. RESULTS: We studied a 57-year-old woman who at the age of 47 years began to have recurrent episodes of fever, myalgias, arthralgias, diffuse abdominal pain, diarrhea, adenopathies, and systemic inflammation, which were relatively well controlled with anti-interleukin-1 (anti-IL-1) drugs. NGS analyses did not detect germline variants in any of the known autoinflammatory disease-associated genes, but they identified the p.Ser171Phe NLRC4 variant in unfractionated blood, with an allele fraction (2-4%) compatible with gene mosaicism. Structural modeling analyses suggested that this missense variant might favor the open, active conformation of the NLRC4 protein, and in vitro and ex vivo analyses confirmed its propensity to oligomerize and activate the NLRC4 inflammasome, with subsequent overproduction of IL-18. CONCLUSION: Our findings indicate that the postzygotic p.Ser171Phe NLRC4 variant is a plausible cause of the disease in the enrolled patient. Functional and structural studies clearly support, for the first time, its gain-of-function behavior, consistent with previously reported NLRC4 pathogenic variants. These novel findings should be considered in the diagnostic evaluation of patients with adult-onset uncharacterized autoinflammatory disease.

A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome/neonatal-onset multisystem inflammatory disease: Novel evidence of the role of low-level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases.

OBJECTIVE: Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a severe, early-onset autoinflammatory disease characterized by an urticaria-like rash, arthritis/arthropathy, variable neurologic involvement, and dysmorphic features, which usually respond to interleukin-1 blockade. CINCA/NOMID has been associated with dominant Mendelian inherited NLRP3 mutations. However, conventional sequencing analyses detect true disease-causing mutations in only approximately 55-60% of patients, which suggests the presence of genetic heterogeneity. We undertook the current study to assess the presence of somatic, nongermline NLRP3 mutations in a sporadic case of CINCA/NOMID. METHODS: Clinical data, laboratory results, and information on treatment outcomes were gathered through direct interviews. Exhaustive genetic studies, including Sanger method sequencing, subcloning, restriction fragment length polymorphism assay, and pyrosequencing, were performed. RESULTS: The patient's CINCA/NOMID was diagnosed based on clinical features (early onset of the disease, urticaria-like rash, knee arthropathy, and dysmorphic features). The patient has exhibited a successful response to anakinra within the last 28 months. Analysis of NLRP3 identified a novel heterozygous variant (p.D303H) that was detected in approximately 30-38% of circulating leukocytes. The absence of this variant in healthy controls and in the patient's parents suggested a de novo true disease-causing mutation. Additional analyses showed that this novel mutation was present in both leukocyte subpopulations and epithelial cells. CONCLUSION: Our findings identify the novel p.D303H NLRP3 variant in a Spanish patient with CINCA/NOMID as a new disease-causing mutation, which was detected as a somatic, nongermline mutation in hematopoietic and nonhematopoietic cell lineages. Our data provide new insight into the role of low-level mosaicism in NLRP3 as the pathophysiologic mechanism underlying cryopyrin-associated periodic syndrome.

Admittances characteristics by sepsis in the Spanish internal medicine services between 2005 and 2015: mortality pattern.

BACKGROUND: Studies in recent years suggest an increase in the incidence of sepsis but a decrease in mortality. The aim of this study is to describe the characteristics of patients discharged after a sepsis episode from Spanish internal medicine services between 2005 and 2015. RESULTS: Since 2005, in which there were a total of 4,319 cases, sepsis hospitalizations has been consistently increasing yearly reaching a total of 25,820 cases in 2015. We observed that septic patients are older and with higher comorbidity than the general population admitted in Internal Medicine. On the other hand, we found a decreasing trend in the mortality rates of patients with sepsis in our series going from 35.7% in 2005 to 30.1% in 2015 (p < 0.005). DISCUSSION: In our study, a higher comorbidity at admission and developing complications during admittance, conditioned a higher probability of death due to sepsis. The variables that were associated with increased mortality risk were age, acute renal failure, acute respiratory failure, lactic acidosis, septic shock and chronic heart failure. CONCLUSION: As in other similar studies, we observed an increase in the hospitalizations by sepsis as a diagnosis at discharge during the study period in Internal Medicine services with a simultaneous decrease in mortality. Comorbidity at admission and complications during admittance condition mortality.

Compassionate use of cefiderocol to treat tissue infection caused by MDR-pseudomonas aeruginosa in a critically-ill patient / Uso compasivo de cefiderocol en el tratamiento de pseudomona multirresistentes en paciente crítico

BACKGROUND: One of the newest antibiotics against multidrug-resistant (MDR) bacteria is Cefiderocol, a siderophore cephalosporin able to overcome most resistance mechanisms, including metallo-beta-lactamases. Several studies are being carried to prove its clinical benefit. CASE PRESENTATION: A 55-year-old male patient was admitted in the ICU undergoing septic shock due to surgical wound infection. Multidrug-resistant Pseudomonasputida grew in blood cultures and Pseudomonas aeruginosa grew in soft tissue cultures. He was treated with colistin and tobramycin, developing nephro and ototoxicity. Compassionate use of cefiderocol was ordered, and the infection was cured within 14 days. CONCLUSIONS: This is the first evidence of cefiderocol treatment in a soft tissue infection within a surgical wound infection. Our experience with cefiderocol in surgical wound infection suggests that it may be helpful in treating infections at that level, but more clinical trials are still needed.

ANTECEDENTES: Uno de los antibióticos más nuevos contra las bacterias multirresistentes (MDR) es el cefiderocol, una cefalos- porina siderófora capaz de superar la mayoría de los mecanismos de resistencia, incluidas las metalobetalactamasas. Se están realizando varios estudios para demostrar su beneficio clínico. PRESENTACIÓN DEL CASO: Paciente masculino de 55 años que ingresó en la UCI con shock séptico por infección de herida quirúrgica. Pseudomonas putida multirresistente creció en hemocultivos y Pseudomonas aeruginosa crecieron en cultivos de tejidos blandos. Fue tratado con colistina y tobramicina, desarrollando nefro y ototoxicidad. Se indicó cefiderocol y la infección se curó en 14 días. CONCLUSIONES: Esta es la primera evidencia de cefiderocol en el tratamiento de una infección de partes blandas dentro de una infección de herida quirúrgica. Nuestra experiencia con cefiderocol en infección de herida quirúrgica sugiere que puede ser útil en el tratamiento de infecciones a ese nivel, pero aún se necesitan más ensayos clínicos.

Effect of NOD2/CARD15 variants in T-cell depleted allogeneic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Three single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene have been associated with the incidence and the severity of acute graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (SCT). We hypothesized that the clinical effect of SNP in NOD2/CARD15 might be different in patients submitted to T-cell-depleted allogeneic SCT, in which donor T cells, the main effectors of GVHD, are eliminated. DESIGN AND METHODS: SNP 8, 12 and 13 in NOD2/CARD15 were studied using a Taqman protocol in 85 patients undergoing HLA-identical, T-cell-depleted SCT and in 71 of their sibling donors. RESULTS: NOD2/CARD15 variants were present in nine (11%) patients and six (8%) donors. The incidences of acute GVHD and chronic GVHD were not associated with either the donors' or recipients' NOD2/CARD15 variants. In contrast, these genetic variants were associated with a lower disease-free survival (17% vs. 48%, p=0.03). Death due to pulmonary infection was more frequent in the group of patients with NOD2/CARD15 variants. In the multivariate analysis, only NOD2/CARD15 variants (RR 2.3, p=0.04) and older age (RR 2.2; p=0.04) were independent prognostic factors for disease-free survival. INTERPRETATION AND CONCLUSIONS: NOD2/CARD15 variants have a deleterious effect on clinical outcome in T-cell-depleted allogeneic SCT, which is independent of GVHD. These results supports the hypothesis that the detrimental effect of NOD2/CARD15 variants in such a transplant setting might be produced by an alteration of the innate immune system more than by activation of the adaptive immune system.

Prolonged length of stay in hospitalized internal medicine patients.

BACKGROUND: Targeting patients with prolonged hospitalizations may represent an effective strategy for reducing average hospital length of stay (LOS). OBJECTIVE: We sought to characterize predictors of prolonged hospitalization among internal medicine patients in an effort to guide future improvement efforts. DESIGN: We conducted a retrospective cohort study using administrative data of internal medicine patients from all hospitals of the Spanish Public Health Service between January 1st, 2005 and December 31st, 2013. Multivariable logistic regression was performed to assess the association between sociodemographic and clinical variables and prolonged LOS, defined as >30days. KEY RESULTS: Of 5,275,139 discharges, 166,470 (3.2%) had a prolonged LOS. Prolonged hospitalizations accounted for 17.4% of total inpatient days and contributed 0.5days to an average LOS of 9.8days during the study period. Prolonged hospitalizations were associated with younger age (odds ratio [OR]: 0.97 per 10-year increase in age, 95% confidence interval [CI]: 0.96-0.98) and male gender (OR 0.88 IC95% 0.87-0.89). Compared to patients without prolonged LOS, prolonged LOS patients were more likely to require a palliative care consult (OR: 2.48, 95% CI: 2.39-2.58), surgery (OR: 6.9 95% CI: 6.8-7.0); and be discharged to a post-acute-care facility (OR: 2.91, 95% CI: 2.86-2.95). CONCLUSIONS: Prolonged hospitalizations in a small proportion of patients were an important contributor to overall LOS and particularly affected complex hospital stays who were not discharged home.

The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination "hot-spot" at the MEFV locus.

Mutations at the MEFV gene cause, with various degrees of penetrance, familial Mediterranean fever (FMF). This disease is more prevalent in the Middle East than elsewhere, and most studies have focused on those populations. However, FMF occurs also in the Western Mediterranean and these populations should be taken into account for a complete view of FMF. We have analyzed intragenic MEFV SNPs in Spanish and Chueta (descendants of converted Jews) FMF patients and controls, and this constitutes the first systematic survey of normal MEFV SNP haplotype structure and variability. Our findings have allowed us to systematize the nomenclature of MEFV haplotypes and show that there is strong linkage disequilibrium (LD) at the MEFV locus and an intragenic recombination hot spot. The high local LD, regardless the recombination hot spot, is responsible for the limited diversity of the MEFV control haplotypes found in the Spanish population and it suggests that it may be a common feature to all Mediterranean populations. The MEFV mutation spectrum in Spain is quite diverse, and similar to those of France and Italy. On the contrary, the Chueta spectrum was poorer and closer to that of North African Jews, suggesting a direct connection with the Jewish diaspora.

Low prevalence of hyponatremia codification in departments of internal medicine and its prognostic implications.

OBJECTIVE: Hyponatremia is the most frequent ionic disorder among ambulatory and hospitalized populations. The aim of the study is to describe the profile of patients admitted to internal medicine departments of Spanish hospitals with a diagnostic codification of hyponatremia in their discharge sheets. METHODS: Data from the Minimum Basic Data Set (MBDS) of discharged patients from all departments of internal medicine (IM) of the Spanish National Health System (NHS) between 2007 and 2010 were analyzed to describe the profile of patients with diagnostic codification of hyponatremia. RESULTS: A total of 2,134,363 admittances were analyzed, identifying 31,933 (1.5%) with a diagnostic code of hyponatremia (18.3% as principal diagnosis and 81.7% as secondary diagnosis). Mortality among patients with codified hyponatremia was markedly higher than in patients without this condition (13.1% vs 9.8% [OR 1.38; 95% CI 1.33-1.41]). Hyponatremia codification was independently associated with a higher risk of readmission (OR 1.33 CI 95% 1.29-1.38). Average length of stay for patients with hyponatremia was 11.67 days (SD 13.01), compared to 9.84 days (SD 11.61) among the general population admitted to IM (p < 0.001). Mean cost per admission in the presence of codified hyponatremia was €4023 (SD €2531), compared to €3537 (SD €2858.02); p < 0.001. Hyponatremia was more prevalent among patients with the following conditions: dementia, chronic and acute renal failure, hepatic cirrhosis, pressure ulcers, heart failure, and depression. CONCLUSIONS: We found an extremely low prevalence of hyponatremia codification in our series (1.5%). Hyponatremia is underreported and undertreated although numerous studies have shown its devastating impact on hospital admittance. The first step in order to improve this situation is to raise awareness among physicians about a problem that despite its high prevalence is still overlooked.

The effects of increasing effective airway diameter on weaning from mechanical ventilation in tracheostomized patients: a randomized controlled trial.

PURPOSE: To determine the effects of deflating the tracheal cuff during disconnections from mechanical ventilation (MV) in tracheostomized patients. METHODS: This was a single-center, randomized trial conducted in a general ICU of a tertiary hospital with regional referral for trauma patients. Patients at high risk of aspiration based on the drink test were excluded. Critically ill tracheostomized patients were randomized to have the tracheal cuff deflated or not during spontaneous breathing trials. Weaning was protocolized on progressive T-tube trials, and patients were considered weaned after 24 consecutive hours disconnected from MV. The primary end point was time to definitive withdrawal of MV; secondary end points were ventilator-associated respiratory infection (pneumonia and/or tracheobronchitis) and swallowing function. Statistical analyses included Cox proportional risk models. RESULTS: We randomized 195 patients and 181 patients completed the study (94 patients with deflated cuff and 87 with inflated cuff). Variables independently related to weaning time in the multivariate analysis were tracheostomy-to-first MV disconnection time (HR 0.5, 95 % CI 0.3-0.8; p < 0.01) and cuff deflation (HR 2.2, 95 % CI 1.5-3; p < 0.01). Respiratory infection was lower in the deflated group (20 vs. 36 %; p = 0.02). Swallowing function improved more in the deflated group (31 vs. 22 %; p = 0.02). CONCLUSION: Under the conditions of our protocol, deflating the tracheal cuff in tracheostomized patients shortens weaning, reduces respiratory infections, and probably improves swallowing.

Admission of nursing home residents to a hospital internal medicine department.

OBJECTIVE: Hospitalization of nursing home residents is costly and potentially exposes residents to iatrogenic disease and psychological harm. DESIGN AND SETTING: In this study, we analyzed the data from the Basic Minimum Data Set of patients hospitalized from the nursing home who were discharged from all the internal medicine departments at the National Health Service hospitals in Spain between 2005 and 2008, according to the data provided by the Ministry of Health and Consumer Affairs. RESULTS: Between January 2005 and December 2008, 2,134,363 patients were admitted to internal medicine departments in Spain, of whom 45,757 (2.1%) were nursing home residents. Overall, 7898 (17.3%) patients died during hospitalization, 2442 (30.91%) of them in the first 48 hours. The following variables were the significant predictors of in-hospital mortality in multivariate analysis: age (odds ratio [OR] 1.02, 95% confidence intervals [CI] 1.02-1.03), female gender (OR 1.13, 95% CI 1.13-1.17), dementia (OR 1.09, 95% CI 1.03-1.16), previous feeding tube (OR 1.34, 95% CI 1.09-1.79), malignant disease (OR 2.03, 95% CI 1.86-2.23), acute infectious disease (OR 1.18, 95% CI 1.12-1.25), pressure sores (OR 1.88, 95% CI 1.62-1.95), acute respiratory failure (OR 2.00, 95% CI 1.90-2.10), and nosocomial pneumonia (OR 2.5, 95% CI 2.23-2.72). CONCLUSIONS: Two of every 100 patients admitted to internal medicine departments came from nursing homes. The rate of mortality is very high in these patients, with almost one third of patients dying in the first 48 hours, which suggests that many of these transfers were unnecessary. The cost of these admissions for 1 year was equivalent to the annual budget of a 300- to 400-bed public hospital in Spain. The mechanism of coordination between nursing homes and public hospitals must be reviewed with the aim of containing costs and facilitating the care of patients in the last days of life.