Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study.

PURPOSE: Craniopharyngiomas (CPGs) are aggressive brain tumors responsible of severe morbidity in children. The best treatment strategies are under debate. Our study evaluates surgical, pituitary, and hypothalamic outcomes of a tailored staged-surgical approach compared to a single-stage radical approach in children with CPGs. METHODS: Multicenter retrospective study enrolling 96 children treated for CPGs in the period 2010-2022. The surgical management was selected after a multidisciplinary evaluation. Primary endpoint includes the inter-group comparison of preservation/improvement of hypothalamic-pituitary function, the extent of resection, and progression-free survival (PFS). Secondary endpoints include overall survival (OS), morbidity, and quality of life (QoL). RESULTS: Gross Total Resection (GTR) was reached in 46.1% of cases in the single-stage surgery group (82 patients, age at surgery 9 ± 4.7 years) and 33.3% after the last operation in the staged surgery group (14 patients age 7.64 ± 4.57 years at first surgery and 9.36 ± 4.7 years at the last surgery). The PFS was significantly higher in patients addressed to staged- compared to single-stage surgery (93.75% vs 70.7% at 5 years, respectively, p = 0.03). The recurrence rate was slightly higher in the single-stage surgery group. No significant differences emerged in the endocrinological, visual, hypothalamic outcome, OS, and QoL comparing the two groups. CONCLUSIONS: In pediatric CPGs' surgical radicality and timing of intervention should be tailored considering both anatomical extension and hypothalamic-pituitary function. In selected patients, a staged approach offers a safer and more effective disease control, preserving psychophysical development.

Genomic characteristics of Staphylococcus aureus strains associated with high within-herd prevalence of intramammary infections in dairy cows.

Staphylococcus aureus is one of the most important causes of mastitis in dairy cattle. Based on previous research, Staph. aureus genotypes with different pathogenic and contagious properties can cause intramammary infection (IMI) and coexist in the same herd. Our study aimed to compare Staph. aureus strains from herds that differed in IMI prevalence using different molecular approaches such as ribosomal spacer (RS)-PCR, multilocus sequence typing (MLST), spa typing, ribotyping, pulsed-field gel electrophoresis (PFGE), and multiplex PCR. For this purpose, 31 dairy herds with Staph. aureus IMI were selected, and 16 of these were chosen for a comparison study: the 8 high-prevalence (HP) herds had Staph. aureus IMI prevalence >28% and the 8 low-prevalence (LP) herds had an IMI prevalence <4%. A total of 650 isolates of Staph. aureus from mammary quarters of all positive cows were genotyped with RS-PCR, a technique based on amplification of a portion of the intergenic spacer 16S-23S rRNA, and a subset of 54 strains was also analyzed by multiplex PCR, ribotyping, PFGE, MLST, and spa typing. The RS-PCR analysis revealed 12 different profiles. Staphylococcus aureus strains isolated from 5 out of 8 HP herds showed a profile identical to the genotype B (GTB), described in previous studies as being strongly associated with high within-herd prevalence of Staph. aureus mastitis and the presence of the genes coding for enterotoxins sea, sed, and sej, a long x-region of spa gene, and 3 lukE fragments. Moreover, all strains isolated in the HP herds possessed genes coding for staphylococcal enterotoxins. In LP herds, a limited number of strains of 6 genotypes, different from those isolated in HP herds, were identified and GTB was not found. Within these genotypes, 4 strains were positive for the mecA gene. Preliminary results and comparison with other genotyping methods confirmed that genotyping by RS-PCR is an accurate, rapid, and inexpensive tool for future field studies on Staph. aureus mastitis strains and generates clinically relevant results.

Metabolism of triglyceride-rich lipoproteins and transfer of lipids to high-density lipoproteins (HDL) in vegan and omnivore subjects.

BACKGROUND AND AIMS: Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein. METHODS AND RESULTS: 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with (14)C-cholesterol oleate and (3)H-triolein: fractional clearance rates (FCR, in min(-1)) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p < 0,05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal (0.024 ± 0.014, 0.030 ± 0.016, N.S.). Cholesteryl ester transfer to HDL was lower in vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p < 0,05). Free-cholesterol, triglyceride and phospholipid transfer were equal, as well as HDL size. CONCLUSION: Remnant removal from circulation, estimated by cholesteryl oleate FCR was faster in vegans, but the lipolysis process, estimated by triglyceride FCR was equal. Increased removal of atherogenic remnants and diminution of cholesteryl ester transfer may favor atherosclerosis prevention by vegan diet.

Technical note: Identification of Prototheca species from bovine milk samples by PCR-single strand conformation polymorphism.

We report the development of a PCR-single strand conformation polymorphism (SSCP) method to identify Prototheca spp. responsible for bovine mastitis: P. zopfii and P. blaschkeae. The method was set up using reference strains belonging to P. zopfii genotype 1, P. zopfii genotype 2, and P. blaschkeae as target species and P. stagnora, and P. ulmea as negative controls. The assay was applied on 50 isolates of Prototheca spp. isolated from bovine mastitic milk or bulk-tank milk samples, and all isolates were identified as P. zopfii genotype 2. We conclude that the described PCR-SSCP approach is accurate, inexpensive, and highly suitable for the identification of P. zopfii genotype 2 on field isolates but also directly on milk, if preceded by a specific DNA extraction method.

Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels. METHODS: Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 microg m(-2) once every 3 weeks. The primary aim of the study was progression-free survival (PFS). RESULTS: No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months. CONCLUSION: NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest.

Extended Endoscopic Endonasal Approach for Suprasellar Craniopharyngioma.

Objectives We illustrate a suprasellar craniopharyngiomas treated with an extended endoscopic endonasal approach (EEEA). Design Case report of a 43-year-old male affected by cerebral lesion located in suprasellar region involving the third ventricle and compressing the neurovascular structures, causing an anterosuperior dislocation of the chiasma. There is a complete disruption of the pituitary stalk that can explain the clinical finding of partial anterior hypopituitarism and hyperprolactinemia. The lesion is characterized by a solid and cystic component. Considering the absence of lateral extension and the suprasellar location of the lesion, an EEEA is preferred. Setting University Hospital "Ospedale di Circolo," Department of Neurosurgery, Varese, Italy. Participants Neurosurgical and ENT Skull Base Team. Main Outcome Measures A bilateral parasagittal approach is performed using a four-hand technique. The first step of the surgery is the preparation of the Hadad's flap. The approach is extended to the planum sphenoidalis to expose the suprasellar region. The lesion is completely removed employing also an ultrasound aspirator. Skull base reconstruction is performed with three-layer technique: graft of fat tissue, fascia lata, and nasoseptal flap. Results No postoperative complications occurred. In the post-op, the patient presents a panhypopituitarism and an improvement in neurological status. The visual deficit remains stable. Post-op magnetic resonance imaging at 1 year documents the complete absence of pathological contrast enhancement. Conclusions EEEA is a feasible approach in treating craniopharyngioma with suprasellar extension. The advantages include optimal visualization, good resection rate, and absence of brain retraction. The link to the video can be found at: https://youtu.be/IYm-8P1jbBo .

Analysis of 10B antitumoral compounds by means of flow-injection into ESI-MS/MS.

Boron neutron capture therapy (BNCT) is a promising binary treatment for cancer. BNCT is based on the ability of the nonradioactive isotope (10)B to capture, with a very high probability, thermal neutrons. This nuclear reaction results in two particles (an alpha and a lithium nucleus). The particles have a high biological effectiveness, which is limited in tissue to approximately the diameter of one cell. If the reaction can be limited to a tumor cell, the physical characteristic opens up the possibility to selectively destroy cancer cells, while sparing the surrounding healthy tissue. Quality control of (10)B-containing compounds and their distribution at present are very important, and different analytical methods have been developed, such as time-of-flight secondary ion mass spectrometry (TOF-SIMS), electron energy loss spectrometry (EELS), prompt gamma analysis and inductively coupled plasma-optical emission spectrometry (ICP-OES). These methods allow the analyses of (10)B, but it is not possible to characterize the specific molecular compounds containing (10)B. For this reason, we propose a fast and quantitative method that permits the determination of closo-undecahydro-1-mercaptododecaborate (BSH) and (10)boron-phenylalanine (BPA) and their eventual metabolites. In particular, (10)B-containing compounds are detected by means of flow-injection electrospray tandem mass spectrometry (FI/ESI-MS/MS). This approach allows the identification of Boron compounds, BSH and BPA, using tandem mass spectrometry, and quantitative analysis is also possible (c.v. +/-4.7%; n = 5; linear range 10-10,000 ng/ml). Furthermore, (10)B-containing compounds were detected in actual biological sample (urine and plasma, diluted 10,000- and 1,000-fold, respectively) injecting a small volume (1 microl) of diluted samples.

Treatment of proteinuric patients with a vegetarian soy diet and fish oil.

Our aim was to determine whether a longer period of treatment with a vegetarian soy diet with addition of fish oil supplements would accentuate the beneficial effects on hyperlipidemia and proteinuria of nephrotic patients we found in a previous study. After an 8-week baseline period on free diet, patients were randomly allocated either on soy diet alone (SD) or to SD plus 5 g/day of fish oil (SD + FO) orally for two months. Then they crossed over to the other treatment for two additional months. They finally resumed eating the free diet for 3 months. We selected 20 outpatients with chronic glomerulonephritis, proteinuria in the nephrotic range, fasting serum cholesterol > 250 mg/dl, mean serum creatinine concentrations 1.75 +/- 0.23 mg/dl. Serum lipid profile, urinary protein loss and nutritional parameters were monitored. With the soy diet, we obtained a significant decrease both of hyperlipidemia and of proteinuria. The effect of the soy diet on proteinuria increased over the 4 months. The addition of a moderate amount (5 g/day) of fish oil in a randomized cross-over design had no further beneficial effect. Stability of serum albumin, transferrin and the body mass index documented good nutritional status. In conclusion, the dietary manipulation with our vegetarian soy diet confirmed the beneficial effects on hyperlipidemia and proteinuria of nephrotic patients. Such effects persisted and even ameliorated after 4 months of diet. The addition of moderate oral supplements of fish oil did not potentiate the beneficial effect.

Platelet and endothelial response with trapidil in patients with peripheral obliterative arteriopathy.

The activity of trapidil, an antiaggregating agent with PDGF antagonist properties, was investigated in order to verify its possible modulating effect in the endothelial and platelet activation. PDGF, t-PA, PAI-1 and ET-1 plasma levels were measured before and after a 2 month treatment period with trapidil 200 mg tablets bid or placebo in 30 patients affected by POA in Fontaine stage II. PDGF and PAI-1 significantly (p < 0.05) increased in the placebo group, and PDGF also in the comparison between treatments (p < 0.05). Aggregation data demonstrate an absence of Ca++ antagonist action of trapidil. The results of this study suggest that trapidil can interfere with the combined vascular and platelet response in atherogenesis.

Platelet-derived growth factor (PDGF) in patients with different degrees of chronic arterial obstructive disease.

Platelet activation and platelet-derived growth factor (PDGF) play a pivotal role in the pathogenesis of atherosclerosis. Evidence has been accumulating that in the evolution of chronic arterial obstructive disease (CAOD) platelets are also crucially important. The aim of the present study was, therefore, to assess plasma levels of PDGF in patients with different degrees of CAOD according to Fontaine. Twenty patients (17 men, 3 women, mean age sixty-eight +/- seven years) with intermittent claudication (Fontaine stage II) entered the study and their PDGF levels were assessed by radioimmunoassay. Ten additional patients (7 men, 3 women, mean age seventy-three +/- seven years) with more severe CAOD (leg pain at rest/skin ulcers) were also studied. Ten healthy subjects (6 men, 4 women, mean age fifty-four +/- six years) comprised the control group. Patients in stage II were reinvestigated after sixty days of a "training" procedure. Patients with both intermittent claudication and more severe disease had higher levels of PDGF than controls (controls 165.9 +/- 119.1 pg/mL; Fontaine stage II 403.5 +/- 218.4; Fontaine stage III/IV 578.1 +/- 637.2: ANOVA P = 0.04) with no difference between the two groups of patients. After the training period, PDGF levels were significantly higher than at baseline (863.7 +/- 819.6 pg/mL vs 403.5 +/- 218.4) but without significant improvement of physical performance. The elevation of PDGF levels in blood from CAOD patients could be the result of marked platelet activation due to interaction with a widely damaged peripheral vasculature. The same was not true for coronary heart disease, in which normal values of PDGF in venous blood were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Spread of risk across financial markets: better to invest in the peripheries.

Risk is not uniformly spread across financial markets and this fact can be exploited to reduce investment risk contributing to improve global financial stability. We discuss how, by extracting the dependency structure of financial equities, a network approach can be used to build a well-diversified portfolio that effectively reduces investment risk. We find that investments in stocks that occupy peripheral, poorly connected regions in financial filtered networks, namely Minimum Spanning Trees and Planar Maximally Filtered Graphs, are most successful in diversifying, improving the ratio between returns' average and standard deviation, reducing the likelihood of negative returns, while keeping profits in line with the general market average even for small baskets of stocks. On the contrary, investments in subsets of central, highly connected stocks are characterized by greater risk and worse performance. This methodology has the added advantage of visualizing portfolio choices directly over the graphic layout of the network.

Physical exercise after knee arthroplasty: a systematic review of controlled trials.

Total knee arthroplasty (TKA) is the gold standard treatment for end-stage knee osteoarthritis. Most patients report successful long-term outcomes and reduced pain after TKA, but recovery is variable and the majority of patients continue to demonstrate lower extremity muscle weakness and functional deficits compared to age-matched control subjects. Given the potential positive influence of postoperative rehabilitation and the lack of established standards for prescribing exercise paradigms after TKA, the purpose of this study was to systematically review randomized, controlled studies to determine the effectiveness of postoperative outpatient care on short- and long-term functional recovery. Nineteen studies were identified as highly relevant for the review and four categories of postoperative intervention were discussed: 1) strengthening exercises; 2) aquatic therapy; 3) balance training; and 4) clinical environment. Optimal outpatient physical therapy protocols should include: strengthening and intensive functional exercises given through land-based or aquatic programs, the intensity of which is increased based on patient progress. Due to the highly individualized characteristics of these types of exercises, outpatient physical therapy performed in a clinic under the supervision of a trained physical therapist may provide the best long-term outcomes after the surgery. Supervised or remotely supervised therapy may be effective at reducing some of the impairments following TKA, but several studies without direct oversight produced poor results. Most studies did not accurately describe the "usual care" or control groups and information about the dose, frequency, intensity and duration of the rehabilitation protocols were lacking from several studies.

Distribution of embutramide and mebezonium iodide in a suicide after tanax injection.

Tanax is a veterinary formulation for euthanasia comprising embutramide, mebezonium iodide and tetracaine. A 37-year-old female was found dead on her bed, with three empty used syringes and a bottle of Tanax beside her body. Three needle puncture marks were observed on the body. The aim of this study was to evaluate the distribution of embutramide and mebezonium iodide in different biological matrices (femoral and cardiac blood, liver, muscle and vitreous humor) using a chromatographic method for the simultaneous determination of the two drugs. A direct and sensitive liquid chromatography-tandem mass spectrometry method was developed in multiple reaction monitoring mode with positive ionization. Lidocaine was used as an internal standard. Limits of detection and quantitation of 0.01 and 0.05 mg/L, respectively, were reached for both compounds. Embutramide levels ranged from 2.74 mg/L in vitreous humor to 5.06 mg/L in femoral blood, while mebezonium iodide was found at widely differing concentrations (ranging from 2.80 mg/kg in muscle to 24.80 mg/kg in liver). The chromatographic method developed for this study provides a very simple and sensitive means for the simultaneous determination of embutramide and mebezonium iodide, the emetic concentrations of which were consistent with suicides reported in the literature.

Observation of a localization transition in quasiperiodic photonic lattices.

We report the observation of the signature of a localization phase transition for light in one-dimensional quasiperiodic photonic lattices, by directly measuring wave transport inside the lattice. Below the predicted transition point an initially narrow wave packet expands as it propagates, while above the transition expansion is fully suppressed. In addition, we measure the effect of focusing nonlinear interaction on the propagation and find it increases the width of the localized wave packets.

Effect of nonlinearity on adiabatic evolution of light.

We investigate the effect of nonlinearity in a system described by an adiabatically evolving Hamiltonian. Experiments are conducted in a three-core waveguide structure that is adiabatically varying with distance, in analogy to the stimulated Raman adiabatic passage process in atomic physics. In the linear regime, the system exhibits an adiabatic power transfer between two waveguides which are not directly coupled, with negligible power recorded in the intermediate coupling waveguide. In the presence of nonlinearity the adiabatic light passage is found to critically depend on the excitation power. We show how this effect is related to the destruction of the dark state formed in this configuration.

Determining global population distribution: methods, applications and data.

Evaluating the total numbers of people at risk from infectious disease in the world requires not just tabular population data, but data that are spatially explicit and global in extent at a moderate resolution. This review describes the basic methods for constructing estimates of global population distribution with attention to recent advances in improving both spatial and temporal resolution. To evaluate the optimal resolution for the study of disease, the native resolution of the data inputs as well as that of the resulting outputs are discussed. Assumptions used to produce different population data sets are also described, with their implications for the study of infectious disease. Lastly, the application of these population data sets in studies to assess disease distribution and health impacts is reviewed. The data described in this review are distributed in the accompanying DVD.

Phosphodiesterase type 5 inhibithors in older males.

Although erectile dysfunction (ED) in older subjects needs a holistic approach, the pathophysiology consists mainly in chronic ischemia with deterioration of cavernous smooth muscles followed by development of corporeal fibrosis. Therefore, phosphodiesterase type 5 (PDE5) inhibition, enhancing vasodilatation in corpora cavernosa, represents a first-line therapy for ED. PDE5 is in fact the major cGMP hydrolizing enzyme in penile corpus cavernosum. The mechanisms of action, the pharmacokinetics and the contraindications of selective PDE5 inhibitors, are described in details. Furthermore, attention is focused on the interaction of PDE5 inhibitors on hypothalamus-pituitary gonadol (HPG) function. Finally, considering that androgens may influence sexual behavior by modifying the central nervous system neurotransmitter targeted system, the potentiation of PDE5 inhibitors with testosterone supplementation may be considered to improve erectile function and quality of life in older males.

New achievement and novel therapeutic applications of PDE5 inhibithors in older males.

Erectile dysfunction (ED) increases in prevalence and severity because of aging processes and related organic, iatrogenic and social problems. Decline of testosterone (T) levels is observed with age and also in illnesses with a common basis of endothelial damage. The T deficiency may lead to decreased energy, mood depression, reduction of sexual desire, but no correlation has been reported between T level and severity of ED, which is mainly a neurovascular disease. In facts, inhibition of phosphodiesterase type 5 (PDE5) isoenzyme with sildenafil, tadalafil and vardenafil enhances vasodilatation in the corpus cavernosum and subsequent penile erection. Absolute pharmacological potency of PDE5 inhibitors is similar and non-selectivity defines the side-effects profile, while their elimination half-life explains not only the different duration of action, but also short and long-term tolerability. Efficacy of PDE5 inhibitors in younger patients is greater in respect to older subjects because of associated pathologies and the decline in hypothalamic-pituitary-gonadal function. T is essential in erectile function, controlling the expression and activity of PDE5 and therefore, androgen supplementation improves therapeutic response to PDE5 inhibitors in hypogonadal subjects. Since sexual behavior is a complex interplay of physical, psychological, and social factors, the possible effect of these drugs on androgen levels and brain function need to be deeply investigated. The ubiquitarious distribution of PDE5 and the availability of selective inhibitory molecules foster newer studies in the treatment of heart failure, pulmonary hypertension, inflammation, and depression. This new progress is certainly contributing to a better medical approach to sexuality and quality of life in aging people.