Spinal anesthesia for endoscopic urological surgery--low dose vs. varying doses of hyperbaric bupivacaine

BACKGROUND AND OBJECTIVE: The aim of this study is to compare the efficiency of low dose vs. varying doses of hyperbaric bupivacaine in spinal anesthesia for endoscopic urological procedures. METHODS: Sixty consecutive patients were studied in a randomized prospective manner. They received either of 5 (Gr I), 7.5 (Gr II) or 10 mg (Gr III) of hyperbaric bupivacaine 0.5% combined with 25 microg of fentanyl, through a 25-gauge W hitacre spinal needle placed in the L3-L4 interspace. Characteristics of sensory and motor block, dose of ephedrine required, secondary effects, the patients, and the surgeons satisfaction, were noted. RESULTS: The maximum number of blocked segments was 14 +/- 1 (Gr I), 15 +/- 2 (Gr II) and 16 +/- 2 (Gr III). Time to T12 regression was significantly shorter for Gr I (53 +/- 13 min) than for Gr II (69 +/- 20 min) or Gr III (94 +/- 14 min). Bromage 3 block was not found in Gr I compared to 4 patients in Gr II and 15 patients in Gr III. The duration of motor block was shorter in Gr 1(51 +/- 18 min) than in Gr II (86 +/- 19 min) and in Gr III (138 +/- 21 min). Ephedrine was used for 16 patients in Gr III (9.8 +/- 12.2 mg), 5 patients in Gr II (3.7 +/- 7.8 mg) and 2 patients in Gr I (0.5 +/- 1.5 mg). The difference is statistically significant between Gr III and the other groups. CONCLUSIONS: These results suggest that the use of a low dose of bupivacaine (5 mg) added to fentanyl (25 microg) for endoscopic urological surgery, resulted in short-acting sensory block, without motor block and a lower incidence of cardiovascular side effects, as compared to either of 7.5 or 10 mg bupivacaine with 25 microg fentanyl.     

Mefloquine pharmacokinetics in healthy subjects and in peptic ulcer patients after cimetidine administration.

The pharmacokinetics of orally administered mefloquine were determined in six healthy male subjects and in six ulcer patients before and after a 3-day course of cimetidine (400 mg morning and evening). Peak plasma concentrations Cmax and AUC0-infinity were similarly and significantly (P < 0.05) increased after cimetidine pretreatement in both healthy subjects and peptic ulcer patients Cmax was increased by 42.4% and 20.5% while AUC0-infinity was increased by 37.5% in healthy and peptic ulcer subjects respectively. The values of t1/2ab absorption and t1/2 beta elimination, total crearance CLT/F and volume of distribution were altered to varying levels after cimetidine treatment but the changes were not statistically significant in both healthy and peptic ulcer subjects. The established long t1/2 beta and this apparent interaction between mefloquine and cimetidine which resulted in increased mefloquine plasma concentration might be of clinical significant in patients with neurological/psychiatric history.     

The effect of magnesium sulfate on large cerebral artery blood flow in preeclampsia.

OBJECTIVES: To determine the effect of a 6 gram intravenous bolus of magnesium sulfate on maternal cerebral blood flow in women with preeclampsia. STUDY DESIGN: Velocity-encoded phase-contrast magnetic resonance imaging studies were performed on twelve preeclamptic women prior to and immediately after infusion of a 6 gram magnesium sulfate loading dose. Cerebral blood flow was determined at the bilateral proximal middle and posterior cerebral arteries. Study participants returned 6 weeks postpartum for a non-pregnant measurement of cerebral blood flow. The Wilcoxon paired-sample test was used with statistical significance defined as p<0.05. RESULTS: There was no significant difference in cerebral vessel diameter nor blood flow for any of the examined arteries between the pre- and post magnesium sulfate therapy states. CONCLUSIONS: The absence of a significant difference in cerebral blood flow of the middle and posterior cerebral arteries before and after infusion of a 6 gram loading dose of magnesium sulfate in women with preeclampsia could suggest the absence of vasoconstriction of the large cerebral arteries in preeclampsia and question the role of magnesium sulfate as a vasodilator of these arteries.     

Changing cause of death profile in Morocco: the impact of child-survival programmes

This study was carried out to evaluate the trends in cause-specific mortality and the impact of child-survival programmes in Morocco. Two national surveys on causes and circumstances of child deaths were conducted in Morocco in 1988 and 1998 (ECCD-1 and ECCD-2 respectively). These surveys were based on a representative sample of deaths of children aged less than five years (432 and 866 respectively). Causes of death were assessed by verbal autopsy and were validated on a subsample of 94 cases. Data on causes of deaths were matched with death rates from demographic surveys (Enquête Nationale Démographique à Passages Répétés and Demographic and Health Survey) to compute cause-specific death rates. Morocco underwent a dramatic mortality decline since independence, and the decline in mortality among children aged less than five years was particularly rapid over the 1988-1997 period, at an average rate of -6% a year, and faster for children (aged 1-4 year(s)) than for infants. The decline in mortality varied markedly by causes of death and was most pronounced for causes due to vaccine-preventable diseases, such as neonatal tetanus, measles, whooping cough, tuberculosis, for diarrhoeal diseases and malnutrition, and for selected infectious diseases. However, mortality due to acute lower respiratory infection (ALRI) outside the neonatal period did not change significantly as was the case for some neonatal conditions (birth trauma and prematurity) and for accidents. The decline in cause-specific mortality could be attributed to the success of public-health programmes: the Expanded Programme on Immunization, the management of diarrhoeal diseases and malnutrition, and the use of antibiotics for selected infectious diseases. It is likely that improvements in living conditions, child-feeding practices, hygiene, and sanitation also contributed to the decline in mortality, although these could not explain the magnitude of the changes for target diseases. In contrast, the ALRI programme, which started after 1997, could not have any effect yet, and conditions of delivery and care of the newborn improved only marginally over the study period.     

Improvement of EGFR Testing over the Last Decade and Impact of Delaying TKI Initiation

Background: Epidermal growth factor receptor (EGFR) is the most common oncogenic mutation in lung adenocarcinoma and tyrosine kinase inhibitors (TKIs) have been considered standard treatment for more than a decade. However, time to initiation of TKIs (TTIT) from diagnosis is often delayed and represents a challenge for clinicians. We aimed to assess the impact of TTIT on clinical outcomes and complications. Method: TTIT was defined as the time between confirmed advanced diagnosis and the initiation of a TKI. Complications during this pre-TKI period were retrospectively collected from all patients with EGFR-mutant non small cell lung cancer (NSCLC) in our institution. Results: 102 patients were diagnosed with EGFR mutated NSCLC between 2006 and 2019. The median PFS and OS were 12.9 and 22.5 months, respectively. TTIT was 5.7 months (95% CI 3.4–8) with a significant decrease in the latter years of this cohort. During the pre-TKI period, 23 patients received chemotherapy as first line treatment, of which 5 developed severe adverse events and 3 were not fit to receive TKI thereafter. Additionally, 29 patients had rapid clinical deterioration before initiation of first line TKI and 16 had to be hospitalized. Among the patients presenting a performance status deterioration, their prognosis was markedly affected compared to the remainder of the cohort (p = 0.01). Conclusion: Our real-world evidence study supports the concept that a delay to treat EGFR mutant NSCLC with TKIs is associated with adverse events, patient progression, hospitalization, and decreased overall survival. Rapid molecular diagnosis, including access to ctDNA technology may circumvent these deleterious delays.     

Increased Functional MEG Connectivity as a Hallmark of MRI-Negative Focal and Generalized Epilepsy

Epilepsy is one of the most prevalent neurological diseases with a high morbidity. Accumulating evidence has shown that epilepsy is an archetypical neural network disorder. Here we developed a non-invasive cortical functional connectivity analysis based on magnetoencephalography (MEG) to assess commonalities and differences in the network phenotype in different epilepsy syndromes (non-lesional/cryptogenic focal and idiopathic/genetic generalized epilepsy). Thirty-seven epilepsy patients with normal structural brain anatomy underwent a 30-min resting state MEG measurement with eyes closed. We only analyzed interictal epochs without epileptiform discharges. The imaginary part of coherency was calculated as an indicator of cortical functional connectivity in five classical frequency bands. This connectivity measure was computed between all sources on individually reconstructed cortical surfaces that were surface-aligned to a common template. In comparison to healthy controls, both focal and generalized epilepsy patients showed widespread increased functional connectivity in several frequency bands, demonstrating the potential of elevated functional connectivity as a common pathophysiological hallmark in different epilepsy types. Furthermore, the comparison between focal and generalized epilepsies revealed increased network connectivity in bilateral mesio-frontal and motor regions specifically for the generalized epilepsy patients. Our study indicated that the surface-based normalization of MEG sources of individual brains enables the comparison of imaging findings across subjects and groups on a united platform, which leads to a straightforward and effective disclosure of pathological network characteristics in epilepsy. This approach may allow for the definition of more specific markers of different epilepsy syndromes, and increased MEG-based resting-state functional connectivity seems to be a common feature in MRI-negative epilepsy syndromes.     

Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study

Background  

Temperature management is used with increased frequency as a tool to mitigate neurological injury. Although frequently used, little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit (ICU). In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury.     

Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy

OBJECTIVES: Adipocytokines, secreted by adipose tissue, may regulate fat metabolism, lipid and glucose homeostasis and insulin sensitivity. We analysed the relations between circulating concentrations of adiponectin, leptin, interleukin-6, tumor necrosis factor alpha and its soluble receptors sTNFR1 and R2, lipodystrophic phenotypes and metabolic alterations in patients under highly active antiretroviral therapy (HAART). METHODS: We studied 131 consecutive HIV-infected males under protease inhibitor (PI)-based HAART, with body mass index < 27 kg/m2 and C-reactive protein (CRP) < 10 mg/l. Patients were classified in four groups according to clinical examination: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). In addition to adipocytokines, we measured plasma fasting levels of triglycerides, cholesterol, cardiovascular risk markers (high-sensitivity CRP and apolipoproteins B/A1 ratio), fasted and 2 h post-glucose loading glycemia and insulinemia and calculated the quantitative insulin sensitivity check index. RESULTS: The patients were HIV-infected and PI-treated for a mean of 8.2 and 1.6 years respectively; 74% presented lipodystrophy, 38% altered glucose tolerance and 42% hypertriglyceridemia. Insulin sensitivity correlated positively with adiponectin and negatively with leptin and interleukin-6. Adiponectin, but not leptin, negatively correlated with all metabolic parameters. Insulin resistance, metabolic defects and cardiovascular risk markers were strongly negatively correlated with the adiponectin/leptin ratio (A/L), and positively with sTNFR1. LA patients had a longer duration of infection but ML patients presented the most severe metabolic alterations, insulin resistance and A/L decrease. CONCLUSIONS: These results suggest that adiponectin and the TNFalpha system are related to lipodystrophy, insulin resistance and metabolic alterations in patients under PI-based HAART. A/L and sTNFR1 could predict insulin sensitivity and potential cardiovascular risk in these patients.     

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group

Introduction

As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection.

Methods

Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study''s objective was to identify pre-operative predictors of early death (<12 months) after a resection.

Results

The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24–85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136–7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038–10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis.

Conclusion

The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.