European Association for Endoscopic Surgery (EAES) consensus on Indocyanine Green (ICG) fluorescence-guided surgery.

BACKGROUND: In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community. METHODS: An expert panel of surgeons has been selected and invited to participate to this project. Systematic reviews of the PubMed, Embase and Cochrane libraries were performed to identify evidence on potential benefits of ICG fluorescence-guided surgery on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by the panel; they were then submitted to all EAES members through a two-rounds online survey and results presented at the EAES annual congress, Barcelona, November 2021. RESULTS: A total of 18,273 abstracts were screened with 117 articles included. 22 statements and 16 recommendations were generated and approved. In some areas, such as the use of ICG fluorescence-guided surgery during laparoscopic cholecystectomy, the perfusion assessment in colorectal surgery and the search for the sentinel lymph nodes in gynaecological malignancies, the large number of evidences in literature has allowed us to strongly recommend the use of ICG for a better anatomical definition and a reduction in post-operative complications. CONCLUSIONS: Overall, from the systematic literature review performed by the experts panel and the survey extended to all EAES members, ICG fluorescence-guided surgery could be considered a safe and effective technology. Future robust clinical research is required to specifically validate multiple organ-specific applications and the potential benefits of this technique on clinical outcomes.

Imaging-based predictors of permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Cardiac conduction abnormalities requiring permanent pacemaker (PPM) implantation are major complications of transcatheter aortic valve replacement (TAVR). We aimed to investigate whether the relationship between prosthetic valve size and cardiac-gated computed tomography (CT)-based aortic root complex measurements can aid in recognizing patients at risk for PPM implantation post-TAVR. METHODS: We included 83 of 114 consecutive patients who underwent TAVR with the Edwards Sapien valve (Edwards Lifesciences, Irving, CA, USA) at our institution. We excluded patients with preexisting PPM, patients who required conversion to an open surgical procedure, and patients without CT data. We assessed the significance of various potential predictors of PPM placement post-TAVR. RESULTS: Following TAVR, eight patients (9.6%) required PPM. Prosthetic valve to sinus of Valsalva (SOV) index was significantly higher in those patients requiring a PPM post-TAVR (84.1 ± 9.3 vs 76.8 ± 7.1, P  =  0.009). CONCLUSIONS: The prosthetic valve size to diameter of SOV index was identified as a novel predictor of PPM implantation after TAVR.

Cardiobacterium hominis endocarditis incidentally diagnosed following an aortic valve replacement surgery.

Background: Cardiobacterum hominis (C. hominis) is the part of the HACEK group (Haemophilus spp, Actinobacillus spp, C. hominis, Eikenella, and Kingella spp) that accounts for the majority of the Gram-negative infective endocarditis cases. Historically, the fastidious characteristics of these microorganisms proved challenging to many clinicians. Advances in microbiological identification of culture-negative endocarditis; however, may be the reason for the rising incidence of these infections. Here, we report an incidentally diagnosed C. hominis endocarditis following an aortic valve replacement. Case report: A healthy 54-year-old gentleman presented after several months of generalized weakness and exertional intolerance. He was found to have a bicuspid aortic valve with regurgitation and underwent aortic valve replacement surgery. Intraoperatively, the patient was found to have a large perforation of the fused leaflet associated with abnormal pink tissue in the aortic valve area. The aortic valve tissue was cultured. Gram-negative rods were isolated 48 h later and were ultimately identified as C. hominis. He was successfully treated with 6 weeks of intravenous ceftriaxone with sterile blood cultures throughout the hospital stay. In retrospect, the patient's valve failure was likely secondary to subacute endocarditis from C. hominis complicated by leaflet perforation. Conclusion: C. hominis is a rare cause of infective endocarditis with an excellent prognosis when timely diagnosed and managed. By reporting this case, we wish to raise awareness of potential asymptomatic infection, particularly amongst patients with underlying native valve abnormalities, new leaflet perforation, and valve insufficiency.

A novel approach to measuring skin elasticity in systemic sclerosis: results from a pilot study.

OBJECTIVES: Systemic sclerosis (SSc) is characterized by progressive fibrosis of various organs, and causes hard, tethered, and inelastic skin. The modified Rodnan score is used to quantify skin involvement, but this method is subjective and user dependent. The aim of this study was to test the ability of a new skin torsion device to measure skin elasticity in patients with SSc. METHODS: The study included 16 female SSc patients and 58 healthy controls. Skin elasticity was assessed on the forearms and backs of the hands using a new hand-held device that gently rotates the skin for 15 s to a maximum of 40 deg, and measures the speed of rotation and the angle of rotation at 15 s. Total and localized modified Rodnan scores were also documented. RESULTS: Measurements produced by the skin torsion device had good intra-subject reproducibility, particularly in the control group. The SSc patients had significantly lower skin elasticity than an age-matched subgroup of control subjects, as determined by the median speed of rotation of the device in the hands (1.91 vs. 2.60 deg/s, p < 0.0001) and forearms (1.84 vs. 2.46 deg/s, p < 0.0001), and the rotation at 15 s in the hands (28.6 vs. 39.0 deg, p < 0.0001) and forearms (27.6 vs. 36.9 deg, p < 0.0001). The presence of SSc disease was the only independent predictor of skin elasticity. CONCLUSIONS: This pilot study has shown the potential value of a new skin torsion device to assess skin involvement in patients with SSc.

Glucose transport and metabolism in cultured human skin fibroblasts.

Human skin fibroblast cultures, seeded at 10(5) cells/5 cm plate and allowed to grow to confluence at approx. 10(6) cells/5 cm plate, utilized a glycolytic mode of metabolism where the ratio of glucose utilized to lactate produced wa 0.62 +/- 0.05 (Zielke, R.H., Ozand, P.T., Tyldon, J.I., Sevdalian, D.A. and Cornblath, M. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 4110-4114) (mean +/- S.E.). When the glucose in the medium was exhausted, the lactate produced during the highly glycolytic phase was then reutilized. In monolayer cultures that had been washed with phosphate-buffered saline, rates of glucose utilization were measured at 0.25 and 2 mM glucose by monitoring the appearance of 3H2O from [5-3H]glucose. Rate of utilization for each concentration of glucose decreased markedly as the cultures became more confluent. This decrease also correlated with a reduced ability to transport glucose as measured by 2-deoxy-[3H]glucose uptake in washed monolayer cultures. In washed confluent culture of fibroblasts, glucose utilization was markedly decreased by the presence of pyruvate and lactate but not by glutamine. The respiratory inhibitors, rotenone and antimycin, did not increase the rate of glucose utilization except when added in combination with pyruvate. We conclude that cultured skin fibroblasts possess a highly glycolytic mode of metabolism but that this mode can become more oxidative in the presence of sufficient quantities of pyruvate and lactate.

Psychophysiologic effects of early lead exposure.

In several separate experiments neonatal rats were intubated daily with 9, 27 or 81 mg lead acetate/kg of body weight throughout their 3-week postnatal period of development. Based on average body weights, the total daily lead intake was 0.156, 0.454 or 1.384 mg lead per animal, respectively (in addition to normal lead intake from the environment). Subtle and specific behavioral changes, involving an inability to attenuate inappropriate behavior in a two-way shuttle or a habit-reversal operant task, occurred in offspring following exposure to a minimum of 0.454 mg lead per day. The specificity of this central dysfunction was such that motor activity was normal, stress responsiveness remained unaffected and simple learning ability was comparable to that of controls. The only indication of a central neurochemical modification accompanying this behavioral defect was a tendency for telencephalic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities to be depressed, suggesting a possible involvement of the cholinergic system. Steady-state levels of brain monoamines were unaltered. The experimental weanlings displayed an inhibition of blood delta-amino levulinic acid dehydratase (ALAD) activity, a parallel reduction in regional brain ALAD activity, a moderate reduction in hematocrit and hemoglobin and an increase in kidney weight. This latter effect occurred even at the lowest level of lead intake, 0.156 mg lead per day.

Neurobehavioral dysfunctions associated with dietary iron overload.

Excessive dietary Fe is known to be toxic, but the extent of neurobiological involvement is not clear. In the present study male weanling rats were fed diets containing Fe at 35 (control), 350, 3500, or 20000 ppm for 12 wk. An Fe-deficient group (4 ppm) was included for comparison. Rats were tested for behavioral and body weight changes at various times after initiation of diets, and liver and brain nonheme Fe were measured at term. Excess dietary Fe, primarily at 20000 ppm, significantly decreased activity, habituation, reflex startle, and conditioned avoidance response performance, and enhanced prepulse modulation of startle. Body weights were also markedly decreased. Fe-deficient animals showed similar behavioral effects but more moderate body weight changes. Liver nonheme Fe varied directly with dietary levels. Whole-brain nonheme Fe was significantly reduced in Fe-deficient animals but increased only at the 20000-ppm level. Homeostatic mechanisms appear to regulate whole-brain Fe more effectively under conditions of dietary Fe overload than under conditions of Fe deficiency. The behavioral changes associated with dietary Fe overload may represent secondary consequences of systemic toxicity.

Development and validation of a bioanalytical method for the determination of the cholecystokinin type-1 (CCK(1)) receptor antagonist dexloxiglumide in human plasma.

A sensitive bioanalytical method for the measurement of dexloxiglumide, a new selective and potent cholecystokinin type-1 (CCK(1)) receptor antagonist, in plasma, is reported. The method is based on reversed-phase liquid chromatography with ultraviolet absorption detection. Samples are extracted under acidic conditions into an organic solvent, and following evaporation, reconstitution and centrifugation stages, the supernatant is injected on to an ODS column with detection at 244 nm. The method has been validated over the concentration range 0.2-20 microgram/ml, 0.2 microgram/ml being the lower limit of quantification. The overall precision and accuracy (expressed as relative error) of the method was less than 6.1 and 2.3%, respectively. Dexloxigulmide was shown to be stable in plasma when stored at -20 degrees C for at least 200 days. The method is suitable for studying the pharmacokinetics of dexloxiglumide in man.

Neurobehavioral effects of the calcium ionophore A23187.

The divalent cationic ionophore A23187 (calimycin) facilitates the transport of calcium ions across biological membranes, resulting in an increase of cytosolic calcium. A23187 has been used extensively in vitro to activate calcium-dependent neurocellular processes. Because of its potential usefulness as a neurotoxicological probe, our laboratory conducted a series of studies to characterize the neurofunctional consequences of A23187 in the intact organism. In addition to approximating the LD50, the effects of acute parenteral administration of A23187 on conditioned avoidance, nociceptive shock threshold, open-field activity, consummatory behavior, body temperature and neuromotor function, including general activity, coordination, balance and grip strength, were assessed in the rodent. The LD50 of A23187, administered intraperitoneally to adult male rats, was 9.2 mg/kg. The predominant overt signs of toxicity included lethargy, limb weakness and apnea. Lower doses, from 0.5 to 0.03 mg/kg, produced a variety of more subtle neurobehavioral effects, including a selective depression of motor activity, a moderate elevation of shock threshold, altered conditioned avoidance behavior and hypothermia.

A novel conjugate as a major metabolite of bromperidol in man.

The major urine metabolites of the neuroleptic drug, bromperidol, after oral doses to rats and dogs are p-fluorophenylacetic acid and its glycine conjugate resulting from oxidative N-dealkylation. While the same metabolites were also detected in human urine, also present was a major unknown component representing 50% of the total urine metabolites, which apparently was not formed by rats and dogs to any extent. Mass spectroscopic investigations a substituent attached to the tertiary hydroxyl group. The mass spectrum of the metabolite after trifluoroacetylation was consistent with an O-glucofuranosiduronolactone conjugate of bromperidol.

High performance liquid chromatographic determination of dothiepin and northiaden in human plasma and serum.

A method has been developed for the separation and measurement of dothiepin and the N-demethyl metabolites, northiaden, in human plasma or serum by high performance liquid chromatography. The method uses a structurally-related drug, amitriptyline, as an internal standard and provides a limit of detection of about 10 ng/ml for each component. At a concentration of 20 ng/ml, northiaden and dothiepin could be measured with +/-11% and +/- 6% of the mean respectively and at 200 ng/ml within +/-3% and 1% of the mean. The method has been applied to the analysis of serum from patients undergoing dothiepin therapy.

Dose-proportional pharmacokinetics of cefepime in rats.

Cefepime (BMY-28142) is a new parenteral cephalosporin antibiotic with excellent activity against a broad-spectrum of clinically important pathogens resistant to other new cephalosporins. A single bolus dose of 10, 20 or 40 mg/kg cefepime was given i.v. to male and female Sprague-Dawley rats from which blood and urine samples were collected. For statistical reasons, pharmacokinetic parameters (AUC, Kel) were derived by fitting an exponential curve to the plasma concentrations; subsequently, contrasts were made between the different doses for AUC and Kel and, in addition, plasma concentrations observed after the first sampling time (Cmax). Cmax and AUC appeared to be linearly related to the administered dose in both males and females. The dose increased in the ratio 1:2:4 and mean Cmax in male and female rats increased in the ratio 1:2.3:4.1 and 1:2.3:4.4 respectively; similarly, AUC increased in the ratio 1:2.2:4.3 and 1:2.0:4.2 respectively. Deviations from linearity and proportionality were not significant (P0.05). The systemic clearance of cefepime in rats was 2.3 ml/min. The volume of distribution was about 60 ml and cefepime appears to be selectively distributed into the extracellular water. Plasma concentrations declined monoexponentially with a mean half-life of 15-20 min which did not significantly change with increasing doses. The renal clearance of cefepime was 1.8 ml/min and approximately 80% of the dose was excreted in the urine unchanged; renal excretion of cefepime is the major route of elimination in rats. The elimination and distribution characteristics of cefepime in rats were similar to those observed in man.

Lack of association between the Tlr4 (Lpsd/Lpsd) genotype and increased susceptibility to Escherichia coli bladder infections in female C3H/HeJ mice.

UNLABELLED: Toll-like receptor 4 is thought to have a primary role in host defense against Escherichia coli bladder colonization, based on mouse models of urinary tract infection using C3H/HeJ female mice. This strain carries a point mutation in the Tlr4 gene, which renders the mice unresponsive to lipopolysaccharide (LPS) and thus limits the bladder inflammatory response and infection resolution. The importance of Tlr4 as the sole genetic determinant of resistance or susceptibility can be questioned, however, by the observation that C3H/HeOuJ female mice with a functional Tlr4 do not effectively resolve E. coli bladder infections. The present study further examined this inconsistency by investigating the association of Tlr4 Lps(d) and Lps(n) alleles with bladder infection susceptibility by using genetic crosses of C3H/HeJ mice with Tlr4 (Lps(n)/Lps(n)) or (Lps(n)/Lps(d)) mice. Heterozygous offspring of C3H/HeJ (Lps(d)/Lps(d)) × BALB/cAnN (Lps(n)/Lps(n)) mice successfully resolved bladder infections induced by a uropathogenic E. coli strain, while heterozygous mice from a C3H/HeJ (Lps(d)/Lps(d)) × C3H/HeOuJ (Lps(n)/Lps(n)) cross had severe infections. A backcross of C3H/HeJ (Lps(d)/Lps(d)) with (BALB/cAnN × C3H/HeJ)F(1) (Lps(n)/Lps(d)) produced mice that were either resistant or susceptible to E. coli bladder infections and had Lps(d)/Lps(d) or Lps(n)/Lps(d) Tlr4 genotypes. The Lps(d)/Lps(d) or Lps(n)/Lps(d) genotypes were present in individual mice with unresolved bladder infections, and the Lps(d)/Lps(d) genotype was found in infection-resistant mice. These results indicate that at least one gene other than Tlr4 strongly influences susceptibility to E. coli bladder infections in C3H/HeJ mice. IMPORTANCE: We have previously demonstrated that mouse strains with either a functional or nonfunctional Tlr4 were not able to resolve induced Escherichia coli bladder infections and that a chromosomal site distinct from Tlr4 was associated with an inability to resolve bladder infections in C3H/HeJ mice. The present study has further investigated the relevance of Tlr4 in bladder infection resolution by defining the Tlr4 alleles present in offspring of genetic crosses of C3H/HeJ mice with infection-resistant and -susceptible inbred strains. The results of these experiments showed that mice with a normal Tlr4 on different genetic backgrounds were not able to clear E. coli bladder infections and that animals with a defective Tlr4 could successfully resolve infections. These results strongly imply the presence of a gene other than in Tlr4 as an important genetic determinant of infection resistance/susceptibility in C3H/HeJ and other inbred mouse strains used in mouse models of infectious diseases.