Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses. STUDY DESIGN AND METHODS: We analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone. RESULTS: Of the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29-0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32-2.36). CONCLUSIONS: Corticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.

Prevention of the spread of multidrug-resistant organisms in nursing homes.

The increase in the aged population led to a global rise in the demand for elderly healthcare services, such as long-term care facilities (LTCFs), nursing homes, residential homes. Unfortunately, the spread of multidrug-resistant organisms (MDROs) in these structures represent an urgent public health threat requiring immediate action. The aim of this review is to provide a practice guide for the prevention of infections in European LTCFs. A team of experts identify specific problems and proposed practical solutions for the management of colonized and infected patients residing in LTCFs. The heterogeneity of LTCF represents one of the main problems for the implementation of standardized surveillance and infection control programs. Crucial steps involved in the spread of infections among LTCF residents are represented by patient's accommodation, MDRO screening on admission, management of patients with rectal colonization by MDROs, management of patients at high risk of MDRO infections, MDRO transmission by staff and implementation of antimicrobial stewardship. Efforts to implement specific actions in each of these fields are required to reduce the infections in this setting.

Experimental colitis in IL-10-deficient mice ameliorates in the absence of PTPN22.

Interleukin (IL)-10 plays a key role in controlling intestinal inflammation. IL-10-deficient mice and patients with mutations in IL-10 or its receptor, IL-10R, show increased susceptibility to inflammatory bowel diseases (IBD). Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) controls immune cell activation and the equilibrium between regulatory and effector T cells, playing an important role in controlling immune homoeostasis of the gut. Here, we examined the role of PTPN22 in intestinal inflammation of IL-10-deficient (IL-10-/- ) mice. We crossed IL-10-/- mice with PTPN22-/- mice to generate PTPN22-/- IL-10-/- double knock-out mice and induced colitis with dextran sodium sulphate (DSS). In line with previous reports, DSS-induced acute and chronic colitis was exacerbated in IL-10-/- mice compared to wild-type (WT) controls. However, PTPN22-/- IL-10-/- double knock-out mice developed milder disease compared to IL-10-/- mice. IL-17-promoting innate cytokines and T helper type 17 (Th17) cells were markedly increased in PTPN22-/- IL-10-/- mice, but did not provide a protctive function. CXCL1/KC was also increased in PTPN22-/- IL-10-/- mice, but therapeutic injection of CXCL1/KC in IL-10-/- mice did not ameliorate colitis. These results show that PTPN22 promotes intestinal inflammation in IL-10-deficient mice, suggesting that therapeutic targeting of PTPN22 might be beneficial in patients with IBD and mutations in IL-10 and IL-10R.

Jumping to conclusions at first onset of psychosis predicts longer admissions, more compulsory admissions and police involvement over the next 4 years: the GAP study.

BACKGROUND: Jumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case-control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years. METHODS: One-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning 'Beads' Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment - the Mental Health Act (MHA) - and inpatient days). RESULTS: FEP who presented JTC at baseline were more likely during the follow-up period to be detained under the MHA [adjusted OR 15.62, 95% confidence interval (CI) 2.92-83.54, p = 0.001], require intervention by the police (adjusted OR 14.95, 95% CI 2.68-83.34, p = 0.002) and have longer admissions (adjusted IRR = 5.03, 95% CI 1.91-13.24, p = 0.001). These associations were not accounted for by socio-demographic variables, IQ and symptom dimensions. CONCLUSIONS: JTC in FEP is associated with poorer outcome as indicated and defined by more compulsion police intervention and longer periods of admission. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programmes.

Awareness of FDA-mandated cigarette packaging changes among smokers of 'light' cigarettes.

Previous research has clearly demonstrated that smokers associate cigarette descriptors such as 'light', 'ultra-light' and 'low tar' with reduced health risks, despite evidence showing that cigarettes with these descriptor terms do not present lower health risk. In June 2010, regulations implemented by the US Food and Drug Administration went into effect to ban the use of 'light', 'mild' and 'low' on cigarette packaging. We surveyed smokers participating in human laboratory studies at our Center in Philadelphia, PA, USA shortly after the ban went into effect to determine the extent of awareness of recent cigarette packaging changes among smokers of light cigarettes. In our sample of 266 smokers, 76 reported smoking light cigarettes, but fewer than half of these smokers reported noticing changes to their cigarette packaging. Simple removal of a few misleading terms may be too subtle of a change to register with consumers of so-called 'low tar' cigarettes; more comprehensive regulation of cigarette packaging design may be necessary to gain smokers' attention and minimize misperceptions associated with tobacco pack design characteristics and color.

A cluster of fulminant Clostridium difficile colitis in an intensive care unit in Italy.

We describe, for the first time, a cluster of lethal fulminant health-care associated Clostridium difficile (CD) colitis in Italy, observed in the intensive care unit (ICU) of an Italian tertiary care hospital in Rome. For all cases the cause of ICU admission was CD-related septic shock. Three out of seven patients were residents in a long-term care facility in Rome, and the others had been transferred to the ICU from different medical wards of the same hospital. Five patients died within 96 h of ICU admission. Because of a clinical deterioration after 4 days of adequate antibiotic therapy, two patients underwent subtotal colectomy: both of them died within 30 days of surgical intervention. In four cases, ribotyping assay was performed and ribotype 027 was recognized. This high mortality rate could be attributable to three findings: the extent of disease severity induced by the strain 027, the delay in antimicrobial therapy administration, and the lack of efficacy of the standard antibiotic treatment for fulminant CD colitis compared to an earlier surgical approach. In order to contain a CD infection epidemic, control and surveillance measures should be implemented, and empirical therapy should be administered. Because of potential 027 ribotype CD spread in Italy, CDI should be regarded with a high index of suspicion in all patients presenting with shock and signs or symptoms suggesting abdominal disease, and an early surgical approach should be considered.

Do psychosis patients with poor insight show implicit awareness on the emotional stroop task?

BACKGROUND: The insight into psychosis can be assessed reliably by clinicians from interviews with patients. However, patients may retain implicit awareness of illness while lacking explicit awareness. SAMPLING AND METHODS: In a sample of first-episode psychosis patients, we used a test of processing of mental illness-related and other negative words as a measure of implicit awareness to see how this varied in relation to insight. An emotional-counting Stroop task tested reaction times to words of three types: psychosis-related (e.g. 'crazy'), general negative (e.g. 'cancer') and neutral (e.g. 'oyster'). Data were available from 43 patients and 23 healthy controls. Patients' insight was assessed using the Schedule for the Assessment of Insight (SAI-E). RESULTS: Patients reacted slower than controls to words across all conditions, and both patients and controls reacted slower to salient and negative words than neutral words. There was a near significant interaction between word type and group (Wilks' lambda = 0.53, p = 0.055); patients experienced greater interference from negative rather than psychosis-related words (p = 0.003), and controls experienced greater interference from salient rather than negative words (p = 0.01). Within the patient group, there was a correlation between insight and interference on salient words (r = 0.33, p = 0.05), such that those with less insight experienced less interference on psychosis-related words. CONCLUSIONS: Psychosis-related words were less threatening and less self-relevant to psychosis patients with less insight. This suggests that the lack of awareness such patients have of their illness is genuine and more likely to be mediated by lower-level information processing mechanisms than strategies such as conscious, motivated denial.

Role of empirical and targeted therapy in hospitalized patients with bloodstream infections caused by ESBL-producing Enterobacteriaceae.

BACKGROUND: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase (ESBL) producing Enterobacteriaceae are a major cause of in-hospital mortality. The effect on survival of empirical and targeted antibiotic therapy in these patients remains controversial. METHODS: A prospective cohort study was conducted analyzing data from 94 patients (age 59 ± 21 years) with BSI due to ESBL producing strains (Sixty-one E. coli, 26 K. pneumoniae, 4 Proteus spp and 3 Enterobacter spp). RESULTS: Risk factors associated with 21-day mortality at univariate analysis were: recent administration of antibiotic therapy (p=0.049), higher SOFA score (p=0.05), ICU stay (p <0.01), hypotension at presentation (p =0.001) or septic shock (p <0.001) and bacteremia from source other than urinary tract (p=0.03). Regardless of antibiotic class used, no differences in survival were noted between patients receiving or not adequate initial antimicrobial treatment (37.1% vs 23.7% p=0.23); on the other hand, compared with the administration of other in vitro active antibiotics, the use of carbapenem as definitive therapy was associated with a significantly lower 21-day mortality (54.3% vs 28.5% p=0.02). CONCLUSIONS: These findings suggest that the administration of an adequate initial therapy is not associated with mortality in hospitalized patients with BSI due to Enterobacteriaceae. The severity of clinical conditions at presentation and the administration of carbapenems as definitive therapy seems to be really important in affecting the outcome of patients with BSI due to ESBL producing strains.

Patient risk factors for outer membrane permeability and KPC-producing carbapenem-resistant Klebsiella pneumoniae isolation: results of a double case-control study.

BACKGROUND: In the 1,200-bed university hospital "Umberto I" in Rome, Italy, we observed a dramatic substitution of a precedingly well-documented Klebsiella pneumoniae clone (ST37) with ertapenem resistance by outer membrane permeability modification (Porin-ER-Kp) with a new K. pneumoniae strain expressing carbapenem resistance due to K. pneumoniae carbapenemase production (KPC-CR-Kp). A case-case-control study was carried out to evaluate risk factors for Porin-ER-Kp and KPC-CR-Kp isolation. METHODS: All patients with hospital-acquired K. pneumoniae isolation between July 2008 and June 2011 were included. Two case groups including patients harbouring KPC-CR-Kp and Porin-ER-Kp were analysed, with a third control group from whom carbapenem-susceptible K. pneumoniae (CS-Kp) were isolated. RESULTS: Forty-four KPC-CR-Kp cases, 39 Porin-ER-Kp cases and 60 CS-Kp controls were analysed. During the 3-year study, a specific Porin-ER-Kp endemic clone (ST37) was substituted by a new KPC-CR-Kp clone (ST512). Breakthrough bacteraemias occurred in 21 out of 26 KPC-CR-Kp group bloodstream infections (BSIs); nine of these developed during carbapenem therapy and seven with colistin and/or tigecycline therapy. In 13 Porin-ER-Kp BSIs, breakthrough bacteraemias developed in eight patients and four during carbapenem therapy. In the multivariable analysis, KPC-CR-Kp isolates were associated with carbapenems [odds ratio (OR) 7.74; 95 % confidence interval (CI) 1.70-35.2; p < 0.01) and endoscopy (OR 6.71; 95 % CI 1.25-36.0; p < 0.03). Porin-ER-Kp independent risk factors included second-generation cephalosporins (OR 25.7; 95 % CI 3.20-206.8; p < 0.01), carbapenems (OR 19.1; 95 % CI 4.34-83.9; p < 0.001), acute renal failure (OR 7.17; 95 % CI 1.33-38.6; p < 0.03), endoscopy (OR 6.12; 95 % CI 1.46-25.6; p < 0.02) and third-generation cephalosporins (OR 5.3; 95 % CI 1.34-20.9; p < 0.02). CONCLUSIONS: Porin-ER-Kp strains needed major antimicrobial pressure compared to KPC-CR-Kp to express resistance. KPC-CR-Kp substituted Porin-ER-Kp strains, causing more infections. KPC-CR-Kp breakthrough bacteraemia occurred even under therapy with tigecycline or colistin, underlining that an antibiotic stewardship programme is needed urgently.

The current and future off-label uses of dalbavancin: a narrative review.

Dalbavancin is a novel long-acting semi-synthetic lipoglycopeptide. It is licensed for acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. Many studies on dalbavancin alternative use in clinical practice have been published recently, including osteomyelitis, prosthetic joint infections (PJIs), and infective endocarditis (IE). Thus, we conducted a narrative review on dalbavancin efficacy in difficult-to-treat infections, such as osteomyelitis, PJIs, and IE. We performed a comprehensive literature search through electronic databases (PubMed-MEDLINE) and search engines (Google Scholar). We included peer-reviewed publications (articles and reviews), and grey literature on dalbavancin use in osteomyelitis, PJIs, and IE. No time or language restrictions have been established. Despite the great interest in clinical practice, only observational studies and case series on the use of dalbavancin in infections other than ABSSSI are available. The reported success rate was extremely variable between studies, ranging from 44% to 100%. A low success rate has been reported for osteomyelitis and joint infections, while in endocarditis, the success rate was higher than 70% in all studies. However, there is no literature agreement about the correct regimen of dalbavancin for this type of infection heretofore. Dalbavancin showed great efficacy and a good safety profile, not only in patients with ABSSSI but also in those with osteomyelitis, PJIs, and endocarditis. Further randomized clinical trials are needed to assess the optimal dosing schedule depending on the site of infection. Implementing therapeutic drug monitoring for dalbavancin may represent the future step to achieving optimal pharmacokinetic/pharmacodynamic target attainment.

Changing Italian nosocomial-community trends and heteroresistance in Staphylococcus aureus from bacteremia and endocarditis.

Bloodstream infections due to Staphylococcus aureus (BSI) are serious infections both in hospitals and in the community, possibly leading to infective endocarditis (IE). The use of glycopeptides has been recently challenged by various forms of low-level resistance. This study evaluated the distribution of MSSA and MRSA isolates from BSI and IE in 4 Italian hospitals, their antibiotic susceptibility--focusing on the emergence of hVISA--and genotypic relationships. Our results demonstrate that the epidemiology of MRSA is changing versus different STs possessing features between community-acquired (CA)- and hospital-acquired (HA)-MRSA groups; furthermore, different MSSA isolated from BSI and IE were found, with the same backgrounds of the Italian CA-MRSA. The hVISA phenotype was very frequent (19.5%) and occurred more frequently in isolates from IE and in both the MSSA and MRSA strains. As expected, hVISA were detected in MRSA with vancomycin minimum inhibitory concentrations (MICs) of 1-2 mg/l, frequently associated with the major SCCmec I and II nosocomial clones; this phenotype was also detected in some MSSA strains. The few cases of MR-hVISA infections evaluated in our study demonstrated that 5 out of 9 patients (55%) receiving a glycopeptide, died. Future studies are required to validate these findings in terms of clinical impact.

Epidemiology, characteristics, and outcome of infective endocarditis in Italy: the Italian Study on Endocarditis.

BACKGROUND: The characteristics of patients with infective endocarditis (IE) vary significantly by region of the world. The aim of this study was to evaluate the contemporary epidemiology, characteristics, and outcome of IE in a large, nationwide cohort of Italian patients. METHODS: We conducted a prospective, observational study at 24 medical centers in Italy, including all the consecutive patients with a definite or possible diagnosis of IE (modified Duke criteria) admitted from January 2004 through December 2009. A number of clinical variables were collected through an electronic case report form and analyzed to comprehensively delineate the features of IE. We report the data on patients with definite IE. RESULTS: A total of 1,082 patients with definite IE were included. Of these, 753 (69.6%) patients had infection on a native valve, 277 (25.6%) on a prosthetic valve, and 52 (4.8%) on an implantable electronic device. Overall, community-acquired (69.2%) was more common than nosocomial (6.2%) or non-nosocomial (24.6%) health care-associated IE. Staphylococcus aureus was the most common pathogen (22.0%). In-hospital mortality was 15.1%. From the multivariate analysis, congestive heart failure (CHF), stroke, prosthetic valve infection, S. aureus, and health care-associated acquisition were independently associated with increased in-hospital mortality, while surgery was associated with decreased mortality. CONCLUSIONS: The current mortality of IE remains high, and is mainly due to its complications, such as CHF and stroke.

A rare case of mycobacterial pseudoaneurysm of the superficial femoral artery.

OBJECTIVE: Extrapulmonary localization of tuberculosis accounts for about 15-20% of cases. Several cases of Mycobacterium tuberculosis with vascular involvement have been described, but only few cases for limb vessels. CASE REPORT: We report the case of a 33-year-old man from Gambia with a symptomatic pseudoaneurysm of the right superficial femoral artery. Total body positron emission tomography/computed tomography with [18F]FDG revealed an active infection. The patient underwent vascular reconstruction with a straight reversed vein graft. Molecular testing for Mycobacterium tuberculosis was non-diagnostic. Cultures of the pseudoaneurysm wall and thrombus removed during surgery grew Mycobacterium tuberculosis. CONCLUSIONS: The diagnosis of vascular tuberculosis infection due to Mycobacterium tuberculosis is a challenge. Epidemiology remains the primary criterion for maintaining a high index of suspicion.

Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells.

Motor neuron diseases (MNDs) are a group of neurological disorders that selectively affect motor neurons. There are currently no cures or efficacious treatments for these diseases. In recent years, significant developments in stem cell research have been applied to MNDs, particularly regarding neuroprotection and cell replacement. However, a consistent source of motor neurons for cell replacement is required. Human embryonic stem cells (hESCs) could provide an inexhaustible supply of differentiated cell types, including motor neurons that could be used for MND therapies. Recently, it has been demonstrated that induced pluripotent stem (iPS) cells may serve as an alternative source of motor neurons, since they share ES characteristics, self-renewal, and the potential to differentiate into any somatic cell type. In this review, we discuss several reproducible methods by which hESCs or iPS cells are efficiently isolated and differentiated into functional motor neurons, and possible clinical applications.

A T helper cell 2 (Th2) immune response against non-self antigens modifies the cytokine profile of autoimmune T cells and protects against experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS), and the most commonly used experimental model for multiple sclerosis. It is mediated by autoreactive T cell clones exhibiting a T helper cell (Th) 1 cytokine profile. Nonencephalitogenic T lymphocytes specific for self or exogenous antigens have been found to suppress encephalitogenic T cell responses and to protect against autoimmune disease. The mechanisms by which exogenous antigens modulate autoimmunity are not fully understood. In this study, we tested the hypothesis that a Th2-type immune response against an exogenous, nonself antigen, keyhole limpet hemocyanin (KLH), by releasing IL-4 in the microenvironment, could shift the cytokine profile of encephalitogenic T cells from an inflammatory Th1 to a protective Th2 type. SJL/J mice were preimmunized with the KLH in incomplete Freund's adjuvant to induce a population of Th2 memory cells that would be expected to release Th2 cytokines when activated by the specific antigen at the time of EAE induction. Four weeks later, mice received an encephalitogenic challenge containing guinea pig myelin in complete Freund's adjuvant with or without KLH. All KLH primed animals not receiving the exogenous antigen at the time of EAE induction developed a severe clinical disease indistinguishable from control mice not KLH primed. In contrast, animals preimmunized and challenged with the encephalitogenic inoculum containing KLH showed either no, or markedly reduced, clinical signs. Enzyme-linked immunospot analysis demonstrated that KLH-specific T cells in the primed mice were producing IL-4 characteristic of Th2 cells. In the KLH-primed and restimulated mice, the cytokine profile of the autoreactive, myelin basic protein-specific T cells was shifted from an inflammatory Th1 towards a protective Th2 type. We infer that the presence of IL-4 secreted by KLH-specific memory Th2 cells in the lymphoid system microenvironment in which the autoreactive T cells were engaged by the encephalitogenic stimulus were able to bias their cytokine profile towards a protective Th2 phenotype. This interpretation is supported by the observation that the protective effect of preimmunization with KLH was overcome by rm-IL-12, which inhibited the production of IL-4 by the Th1 cells and biased the autoimmune response to a predominantly Th1 type. Since IL-4 mRNA could not be detected by reverse transcriptase PCR in the CNS, the protective effect was inferred to be mediated by Th2 cells in the lymphoid system, and not the target organ. We conclude that exogenous, nonself antigens that can induce Th2 responses, can modify the cytokine environment sufficiently to alter the cytokine phenotype of inflammatory, autoreactive T cell clones, and ultimately, to provide significant protection against EAE and possibly other T cell-mediated autoimmune diseases.

A defect in interleukin 12-induced activation and interferon gamma secretion of peripheral natural killer T cells in nonobese diabetic mice suggests new pathogenic mechanisms for insulin-dependent diabetes mellitus.

The function of natural killer T (NKT) cells in the immune system has yet to be determined. There is some evidence that their defect is associated with autoimmunity, but it is still unclear how they play a role in regulating the pathogenesis of T cell-mediated autoimmune diseases. It was originally proposed that NKT cells could control autoimmunity by shifting the cytokine profile of autoimmune T cells toward a protective T helper 2 cell (Th2) type. However, it is now clear that the major function of NKT cells in the immune system is not related to their interleukin (IL)-4 secretion. In fact, NKT cells mainly secrete interferon (IFN)-gamma and, activated in the presence of IL-12, acquire a strong inflammatory phenotype and cytotoxic function.

Altered hand proprioception following regional anesthesia as a cause of traumatic jersey finger: Report of two cases.

The sense of body ownership is being increasingly studied by manipulating incoming signals from the periphery with local anesthetics. We sought to understand how altered proprioception induced by anesthesia triggered a traumatic jersey finger, immediately postoperatively, in two patients who underwent surgical carpal tunnel release. Multiple mechanisms contributed to these postoperative injuries associated with a fall. Hand anesthesia deprives the brain of important afferent sensory information and modifies hand size perception in the brain. Moreover, it blocks efferent motor signals that contribute to the perception of hand position with sensory afferent signals. When the patients fell, their movement control was inadequate, generating a strong contraction of the hand extrinsic flexor muscles, against forceful distal phalanx extension. Lastly, both patients had removed their numb operated hand from their arm sling. Disrupted sensory and motor paths modify self-attribution of the hand, and thus halt adequate efferent commands. Protecting the operated hand until full sensory and motor control is regained could have prevented such rare accidents from happening. Level of evidence: V.