Impact of preoperative central neurologic dysfunction on patients undergoing emergency surgery for type a dissection.

BACKGROUND: Preoperative central neurologic deficits in the context of acute type A dissection are a complex comorbidity and difficult to handle. The aim this study was to analyze this subgroup of patients by comparing them with neurologically asymptomatic patients with type A dissection. Results may help the surgeon in preoperative risk assessment and thereby aid in the decision-making process. METHODS: We reviewed the data of patients admitted for acute type A dissection during the period from 1999 to 2010. Associated risk factors, time to surgery from admission, extension of the dissection, localization of central nervous ischemic lesions, and the influence of perioperative brain protective strategies were analyzed in a comparison of preoperative neurologically deficient to nondeficient patients. RESULTS: Forty-seven (24.5%) of a total of 192 patients had new-onset central neurologic symptoms prior to surgery. Concomitant myocardial infarction (OR 4.9, 95% CI 1.6-15.3, P = 0.006), renal failure (OR 5.9, 95% CI 1.1-32.8, P = 0.04), dissected carotid arteries (OR 9.2, 95% CI 2.4-34.7, P = 0.001), and late admission to surgery at >6 hours after symptom onset (OR 2.7, 95% CI 1.1-6.8, P = 0.04) were observed more frequently in neurologically deficient patients. These patients had a higher 30-day in-hospital mortality on univariate analysis (P = 0.01) and a higher rate of new postoperative neurologic deficits (OR 9.2, 95% CI 2.4-34.7, P = 0.02). Neurologic survivors had an equal hospital stay, and 67% of them had improved symptoms. CONCLUSIONS: The predominance of neurologic symptoms at admission may be responsible for an initial misdiagnosis. The concurrent central nervous system ischemia and myocardial infarction explains a higher mortality rate and a more extensive "character" of the disease. Neurologically deficient patients are at higher risk of developing new postoperative neurologic symptoms, but prognosis for the neurologic evolution of survivors is generally favorable.

Bihippocampal damage with emotional dysfunction: impaired auditory recognition of fear.

A right-handed man developed a sudden transient, amnestic syndrome associated with bilateral hemorrhage of the hippocampi, probably due to Urbach-Wiethe disease. In the 3rd month, despite significant hippocampal structural damage on imaging, only a milder degree of retrograde and anterograde amnesia persisted on detailed neuropsychological examination. On systematic testing of recognition of facial and vocal expression of emotion, we found an impairment of the vocal perception of fear, but not that of other emotions, such as joy, sadness and anger. Such selective impairment of fear perception was not present in the recognition of facial expression of emotion. Thus emotional perception varies according to the different aspects of emotions and the different modality of presentation (faces versus voices). This is consistent with the idea that there may be multiple emotion systems. The study of emotional perception in this unique case of bilateral involvement of hippocampus suggests that this structure may play a critical role in the recognition of fear in vocal expression, possibly dissociated from that of other emotions and from that of fear in facial expression. In regard of recent data suggesting that the amygdala is playing a role in the recognition of fear in the auditory as well as in the visual modality this could suggest that the hippocampus may be part of the auditory pathway of fear recognition.

c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo.

Altered synaptic function is considered one of the first features of Alzheimer disease (AD). Currently, no treatment is available to prevent the dysfunction of excitatory synapses in AD. Identification of the key modulators of synaptopathy is of particular significance in the treatment of AD. We here characterized the pathways leading to synaptopathy in TgCRND8 mice and showed that c-Jun N-terminal kinase (JNK) is activated at the spine prior to the onset of cognitive impairment. The specific inhibition of JNK, with its specific inhibiting peptide D-JNKI1, prevented synaptic dysfunction in TgCRND8 mice. D-JNKI1 avoided both the loss of postsynaptic proteins and glutamate receptors from the postsynaptic density and the reduction in size of excitatory synapses, reverting their dysfunction. This set of data reveals that JNK is a key signaling pathway in AD synaptic injury and that its specific inhibition offers an innovative therapeutic strategy to prevent spine degeneration in AD.

Emerging roles of non-coding RNAs in pancreatic β-cell function and dysfunction.

Pancreatic β-cells play a central role in glucose homeostasis by tightly regulating insulin release according to the organism's demand. Impairment of β-cell function due to hostile environment, such as hyperglycaemia and hyperlipidaemia, or due to autoimmune destruction of β-cells, results in diabetes onset. Both environmental factors and genetic predisposition are known to be involved in the development of the disease, but the exact mechanisms leading to β-cell dysfunction and death remain to be characterized. Non-coding RNA molecules, such as microRNAs (miRNAs), have been suggested to be necessary for proper β-cell development and function. The present review aims at summarizing the most recent findings about the role of non-coding RNAs in the control of β-cell functions and their involvement in diabetes. We will also provide a perspective view of the future research directions in the field of non-coding RNAs. In particular, we will discuss the implications for diabetes research of the discovery of a new communication mechanism based on cell-to-cell miRNA transfer. Moreover, we will highlight the emerging interconnections between miRNAs and epigenetics and the possible role of long non-coding RNAs in the control of β-cell activities.

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.

Implication of Nerve Growth Factor in intestinal mucosal mast cell activity and colonic motor alterations in a model of ovalbumin-induced gut dysfunction in rats

We determined NGF involvement in MMCs and colonic motor alterations in an ovalbumin (OVA)-induced gut dysfunction model in rats. Animals received OVA (6 weeks), with/without simultaneous K252a (TrkA antagonist) treatment. MMCs, rat mast cell protease II (RMCPII) levels and colonic contractility in vitro were assessed. OVA increased MMC density and RMCPII concentration. Spontaneous contractility was similar in both groups and inhibited by K252a. Carbachol responses were increased by OVA in a K252a-independent manner. NO-synthase inhibition increased spontaneous activity in OVA-treated animals in a K252a-dependent manner. These observations support an involvement of NGF in the functional changes observed in this model.

Immune Dysfunction and the Pathogenesis of AIDS-associated non-Hodgkin's Lymphoma

Much has been learned about how HIV-induced immune dysfunction contributes to B cell hyperactivation, and potentially, to the pathogenesis of AIDS-lymphoma. However, further studies are needed to fully understand how HIV infection and immune dysfunction promote B cell hyperactivation and the development/growth of AIDS-lymphoma. In particular, studies are needed to define the role of HHV8 vIL6, IL6 receptor-expression, and lymphocyte surface stimulatory molecules, in promoting B cell hyperactivation or lymphoma cell growth.

Qualité des données fournies par la statistique médicale VESKA: le cas de la fracture du fémur proximal. [Quality of data provided by VESKA medical statistics: the case of the fractured proximal femur].

Within the framework of a retrospective study of the incidence of hip fractures in the canton of Vaud (Switzerland), all cases of hip fracture occurring among the resident population in 1986 and treated in the hospitals of the canton were identified from among five different information sources. Relevant data were then extracted from the medical records. At least two sources of information were used to identify cases in each hospital, among them the statistics of the Swiss Hospital Association (VESKA). These statistics were available for 9 of the 18 hospitals in the canton that participated in the study. The number of cases identified from the VESKA statistics was compared to the total number of cases for each hospital. For the 9 hospitals the number of cases in the VESKA statistics was 407, whereas, after having excluded diagnoses that were actually "status after fracture" and double entries, the total for these hospitals was 392, that is 4% less than the VESKA statistics indicate. It is concluded that the VESKA statistics provide a good approximation of the actual number of cases treated in these hospitals, with a tendency to overestimate this number. In order to use these statistics for calculating incidence figures, however, it is imperative that a greater proportion of all hospitals (50% presently in the canton, 35% nationwide) participate in these statistics.

Estudio del bypass gástrico en Y de Roux y de la gastrectomía tubular sobre el metabolismo de la glucosa y la secreción de hormonas intestinales. Estudio prospectivo y randomizado

Introducció: El bypass gàstric en Y de Roux laparoscòpic (BGYRL) és la tècnica quirúrgica d’elecció per al tractament de l’obesitat mòrbida. La gastrectomia tubular laparoscòpica (GTL) és una tècnica bariàtrica restrictiva amb resultats molt prometedors en relació a la pèrdua de pes, però se’n desconeixen els efectes metabòlics i endocrins. L’objectiu d’aquest estudi és l’avaluació de les diferències en la resposta del metabolisme de la glucosa i la secreció d’hormones intestinals entre ambdós procediments. Material i mètodes: Es va dissenyar un estudi prospectiu i aleatoritzat per la realització del BGYRL i la GTL, ambdós realitzats via laparoscòpica. Totes les pacients es varen avaluar abans, i als 3 i 12 mesos de la intervenció. Se’ls va prendre una mostra de sang venosa després d’un dejuni de 12 hores i als 10 i 60 minuts després de la ingesta d’Ensure® 420 kcal per realitzar les determinacions dels nivells plasmàtics de glucosa, insulina, grelina, leptina, pèptid relacionat amb glucagó (GLP-1), pèptid YY (PYY) i polipèptid pancreàtic (PP). Resultats: Es varen incloure 15 pacients (totes de gènere femení, edat mitja de 48±9 anys, IMC de 44±2.7 kg/m2 amlitat preoperatòria) dels quals 7 van ser aleatoritzats a BGYRL i 8 a GTL. No hi van haver diferències entre ambdós grups en edat, IMC preoperatori, classificació ASA i determinacions hormonals preoperatòries. Després de la cirurgia, s’observa un descens de la glicèmia i insulinèmia, amb una reducció de l´índex HOMA-IR en ambdós grups. Postoperatòriament, es detecta una disminución de les concentracions de la leptina en dejú i després de la ingesta, significativament menor en el grup de BGYRL. Mentre que els nivells de grelina en dejú només descendeixen de forma significativa en el grup de la GTL. Després de la ingesta es produeix una augment dels nivells de GLP-1, significativament major en el grup de BGYRL. Conclusions: Tan el BGYRL como la GTL s’associen a una significativa pèrdua de pes, encara que aquesta fou significativament superior en el BGYRL. Ambdós procediments han millorat notablement l’homeostasi de la glucosa. Només la GTL va rehuir els nivells de grelina tan en dejú com després de la ingesta, mentre que els nivells de GLP-1 i PYY s’elevaren després de la cirurgia, sense diferències estadísticament significatives entre ambdues tècniques.

Estudio prospectivo comparando la gastrectomía tubular laparoscópica y la gastrectomía robótica para el tratamiento de la obesidad mórbida

La cirurgia de l’obesitat suposa una eina dins de l’arsenal terapèutic dels pacients afectes d’obesitat mòrbida. La gastrectomia vertical s’ha popularitzat com a tècnica i les noves tecnologies com la laparoscòpia s’utilitzen de forma habitual. Més recentment la robòtica s’utilitza en diferents àmbits i també s’està implementant en la cirurgia de l’obesitat. A fi de compara la gastrectomia vertical realitzada mitjançant laparoscòpia o robòtica es planteja el següent estudi. S’han comparat els pacients intervinguts de gastrectomia vertical laparoscòpica i robòtica en termes de complicacions intraoperatòries, morbimortalitat i resultats en el seguiment dels pacients. Els resultats són satisfactoris en el sentit que es demostra que la tecnologia robòtica aporta els mateixos resultats en termes de complicacions intra y perioperatòries. Tanmateix es demostra que l’evolució ponderal dels pacients intervinguts de gastrectomia vertical amb tecnologia robòtica es igual a aquells intervinguts de manera tradicional. Així, es conclou que la tecnologia robòtica es una eina en ple desenvolupament que ha demostrat ser eficient, segura y eficaç per al tractament de la Obesitat Mòrbida mitjançant la Gastrectomia vertical.

Resultats a llarg termini del tractament quirúrgic de les fractures d’húmer proximal intervingudes mitjançant sutures aïllades o associades a claus d’Ender modificats

Valorem els resultats funcionals i de qualitat de vida a mig i a llarg termini de 38 fractures de l’húmer proximal, tractades en 17 casos amb fixació amb sutures transòssies i en 21 associant claus d’Ender modificats. Els pacients intervinguts amb sutures transòssies obtingueren millors resultats funcionals amb diferències significatives. Les fractures en 3 parts en valg obtingueren millors resultats funcionals que les desplaçades en var No s’observaren diferències de qualitat de vida segons tècnica quirúrgica i tipus de fractura. La fixació amb sutures associades o no a claus d’Ender modificats és una tècnica, útil, segura i amb baix índex de complicacions.

Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study.

BACKGROUND: A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort. METHODS: We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model. RESULTS: Two-year event-free probabilities were 0.65 (95% confidence interval [CI] 0.58-0.72) and 0.80 (95% CI 0.76-0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio [HR] = 2.34 [95% CI 1.24-4.42]), higher baseline cGFR (HR = 1.03 [95% CI 1.02-1.04] by 10 ml/min), TDF use (HR = 1.84 [95% CI 1.35-2.51]) and boosted protease inhibitor use (HR = 1.71 [95% CI 1.30-2.24]) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency. CONCLUSION: There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.

Effects of a dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240, on endocrine and renal functions in healthy volunteers.

OBJECTIVE: To investigate the endocrine and renal effects of the dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240. DESIGN: A randomized, placebo-controlled, crossover study was performed in 12 healthy volunteers. METHODS: MDL 100,240 was administered intravenously over 20 min at single doses of 6.25 and 25 mg in subjects with a sodium intake of 280 (n = 6) or 80 (n = 6) mmol/day. Measurements were taken of supine and standing blood pressure, plasma angiotensin converting enzyme activity, angiotensin II, atrial natriuretic peptide, urinary atrial natriuretic peptide and cyclic GMP excretion, effective renal plasma flow and the glomerular filtration rate as p-aminohippurate and inulin clearances, electrolytes and segmental tubular function by endogenous lithium clearance. RESULTS: Supine systolic blood pressure was consistently decreased by MDL 100,240, particularly after the high dose and during the low-salt intake. Diastolic blood pressure and heart rate did not change. Plasma angiotensin converting enzyme activity decreased rapidly and dose-dependently. In both the high- and the low-salt treatment groups, plasma angiotensin II levels fell and renin activity rose accordingly, while plasma atrial natriuretic peptide levels remained unchanged. In contrast, urinary atrial natriuretic peptide excretion increased dose-dependently under both diets, as did urinary cyclic GMP excretion. Effective renal plasma flow and the glomerular filtration rate did not change. The urinary flow rate increased markedly during the first 2 h following administration of either dose of MDL 100,240 (P < 0.001) and, similarly, sodium excretion tended to increase from 0 to 4 h after the dose (P = 0.07). Potassium excretion remained stable. Proximal and distal fractional sodium reabsorption were not significantly altered by the treatment. Uric acid excretion was increased. The safety and clinical tolerance of MDL 100,240 were good. CONCLUSIONS: The increased fall in blood pressure in normal volunteers together with the preservation of renal hemodynamics and the increased urinary volume, atrial natriuretic peptide and cyclic GMP excretion distinguish MDL 100,240 as a double-enzyme inhibitor from inhibitors of the angiotensin converting enzyme alone. The differences appear to be due, at least in part, to increased renal exposure to atrial natriuretic peptide following neutral endopeptidase blockade.

Morbi-mortalidad en fracturas de húmero proximal tratadas quirúrgicamente

L’objectiu es valorar si els pacients afectats de fractura d’húmer proximal tractats quirúrgicament tenen menys morbi-mortalitat a mig termini que els que presenten una fractura de fèmur proximal tractada quirúrgicament. Observem una menor mortalitat en les fractures d’húmer proximal amb un 14.43% respecte al 36% de les fractures de maluc als 8 anys de seguiment. El 79.5% dels pacients amb fractures d’húmer continuen essent independents per a les activitats de la vida diària. Un 26% han tingut fractures posteriors a la fractura d’húmer i un 11.3% ja estaven diagnosticats d’osteoporosis amb anterioritat.