Dental plaque quantitation by light induced fluorescence technology in exclusive Electronic Nicotine Delivery Systems (ENDS) users.

OBJECTIVES: In comparison to conventional combustible cigarettes, Electronic Nicotine Delivery Systems (ENDS) including both e-cigarettes (ECs) and heated tobacco products (HTPs) significantly reduce exposure to toxic chemical emissions. However, their impact on dental plaque remains unclear. This study measures dental plaque in ENDS (ECs and HTPs) users using quantitative light-induced fluorescence (QLF) technology, comparing them with current, former, and never smokers. METHODS: This cross-sectional study compared dental plaque measurements using QLF technology (Q-ray cam™ Pro) among current smokers (≥10 cigarettes/day), former smokers (quit ≥6 months), never smokers, and exclusive ENDS users (quit ≥6 months). Dental plaque measurements were expressed as ΔR30 (total area of mature dental plaque) and ΔR120 (greater plaque thickness/maturation-calculus). The Simple Oral Hygiene (SOH) score was calculated by the QLF proprietary software. Statistical analyses including ANCOVA was performed by R version (4.2.3) with p < 0.05. RESULTS: A total 30 smokers, 24 former smokers, 29 never smokers, and 53 ENDS users were included. Current smokers had significantly higher ΔR30 and ΔR120 values compared to other groups (p < 0.001). ENDS users showed plaque levels similar to never and former smokers (p > 0.05) but significantly lower than current smokers (p < 0.01). Although ENDS users showed a lower SOH score than smokers, this difference was not statistically significant. Daily toothbrushing and mouthwash usage were significant covariates. CONCLUSION: ENDS users exhibited reduced accumulation of dental plaque and calculus compared with current smokers. CLINICAL SIGNIFICANCE: Exclusive ENDS use could less impact dental plaque accumulation compared to cigarette smoking. Further research is needed to confirm these findings and fully understand ENDS impact on dental plaque formation.

The professional background of a referring physician predicts the diagnostic yield of small bowel capsule endoscopy in suspected small bowel bleeding.

Background and study aims The diagnostic yield of small-bowel capsule endoscopy (SBCE) in suspected small bowel bleeding (SSBB) is highly variable. Different reimbursement systems and equipment costs also limit SBCE use in clinical practice. Thus, minimizing non-diagnostic procedures is advisable. This study aimed to assess the SBCE diagnostic yield and identify factors predicting diagnostic findings in a cohort of patients with SSBB. Patients and methods In this retrospective cohort study, we analyzed the medical records of patients who consecutively underwent SBCE for SSBB over 9 years. By logistic regression, we identified covariates predicting diagnostic findings at SBCE. Finally, we performed a post-hoc cost analysis based on previous gastroenterologist or endoscopist consultations versus direct SBCE ordering by other specialists. Results The final analysis included 584 patients. Most SBCEs were ordered by a gastroenterologist or endoscopist (74%). The number of SBCEs without any finding was significantly lower in the gastroenterologist/endoscopist group P <0.001). The SBCE diagnostic yield ordered by a gastroenterologist or endoscopist was significantly higher than that by other specialists (63% vs 52%, odds ratio [OR] 1.57; 95% confidence interval [CI] 1.07-2.26, P =0.019). At multivariate analysis, older age (OR 1.7, 95%CI 1.2-2.4, P =0.005), anemia (OR 4.9, 95%CI 1.9-12, P =0.001), small bowel transit time (OR 1, 95%CI 1-1.02, P =0.039), and referring physician (OR 1.8, 95%CI 1.1-2.7, P =0.003) independently predicted diagnostic findings. Implementing prior gastroenterologist or endoscopist referral vs direct SBCE ordering would reduce medical expenditures by 16%. Conclusions The professional background of referring physicians significantly improves the diagnostic yield of SBCE and contributes to controlling public health costs.

Awake laparoscopic cholecystectomy: A case report and review of literature.

BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the most widely practiced surgical procedures in abdominal surgery. Patients undergo LC during general anaesthesia; however, in recent years, several studies have suggested the ability to perform LC in patients who are awake. We report a case of awake LC and a literature review. CASE SUMMARY: A 69-year-old patient with severe pulmonary disease affected by cholelithiasis was scheduled for LC under regional anaesthesia. We first performed peridural anaesthesia at the T8-T9 level and then spinal anaesthesia at the T12-L1 level. The procedure was managed in total comfort for both the patient and the surgeon. The intra-abdominal pressure was 8 mmHg. The patient remained stable throughout the procedure, and the postoperative course was uneventful. CONCLUSION: Evidence has warranted the safe use of spinal and epidural anaesthesia, with minimal side effects easily managed with medications. Regional anaesthesia in selected patients may provide some advantages over general anaesthesia, such as no airway manipulation, maintenance of spontaneous breathing, effective postoperative analgesia, less nausea and vomiting, and early recovery. However, this technique for LC is not widely used in Europe; this is the first case reported in Italy in the literature. Regional anaesthesia is feasible and safe in performing some types of laparoscopic procedures. Further studies should be carried out to introduce this type of anaesthesia in routine clinical practice.

Autoimmune liver diseases and SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.

CeO2-rGO Composites for Photocatalytic H2 Evolution by Glycerol Photoreforming.

The interaction between CeO2-GO or CeO2-rGO and gold as co-catalysts were here investigated for solar H2 production by photoreforming of glycerol. The materials were prepared by a solar photoreduction/deposition method, where in addition to the activation of CeO2 the excited electrons were able to reduce the gold precursor to metallic gold and the GO into rGO. The presence of gold was fundamental to boost the H2 production, whereas the GO or the rGO extended the visible-light activity of cerium oxide (as confirmed by UV-DRS). Furthermore, the strong interaction between CeO2 and Au (verified by XPS and TEM) led to good stability of the CeO2-rGO-Au sample with the evolved H2 that increased during five consecutive runs of glycerol photoreforming. This catalytic behaviour was ascribed to the progressive reduction of GO into rGO, as shown by Raman measurements of the photocatalytic runs. The good charge carrier separation obtained with the CeO2-rGO-Au system allowed the simultaneous production of H2 and reduction of GO in the course of the photoreforming reaction. These peculiar features exhibited by these unconventional photocatalysts are promising to propose new solar-light-driven photocatalysts for green hydrogen production.

Progression Free Survival, Overall Survival, and Relapse Rate in Endometrioid Ovarian Cancer and Synchronous Endometrial-Ovarian Endometrioid Cancer (SEO-EC): Results from a Large Retrospective Analysis.

Background and Objectives: We aimed to evaluate Progression Free Survival (PFS), Overall Survival (OS), and relapse rate in women affected by endometrioid ovarian cancer and synchronous endometrial-ovarian endometrioid cancer (SEO-EC). As secondary outcome, we assessed whether systematic pelvic and para-aortic lymphadenectomy could be considered a determinant of relapse rate in this population. Materials and Methods: We performed a retrospective analysis of women with diagnosis of endometrioid ovarian cancer or SEO-EC between January 2010 to September 2020, and calculated PFS, OS and relapse rate. Results: In almost all the patients (97.6%) who underwent systematic pelvic and para-aortic lymphadenectomy, there were no lymph node metastases confirmed by histology. We did not find a significant difference (p = 0.6570) for the rate of relapse in the group of women who underwent systematic pelvic and para-aortic lymphadenectomy (4/42; 9.5%) compared with the group of women who did not undergo the same procedure (1/21; 4.8%). During a median follow-up was 23 months, both PFS and OS were excellent. Conclusions: Women affected by early-stage low-grade endometrioid cancer and SEO-EC without apparent lymph node involvement at pre-operative imaging showed a very low rate of lymph node metastasis and similar relapse rate with or without lymphadenectomy.

Fosfomycin Pharmacokinetic Profile in Plasma and Urine and Quantitative Estimation in Prostate and Seminal Vesicles after One and Two Consecutive Doses of Oral Fosfomycin Trometamol in Healthy Male Volunteers.

The present Phase I study investigated, for the first time, fosfomycin pharmacokinetics in humans after two 3 g doses of fosfomycin trometamol administered 27 h apart, according to the dose regimen recommended for the prophylactic indication for transrectal prostate biopsy in adult men. Plasma, urine and seminal plasma concentrations were measured after one and two consecutive doses in 24 healthy men, representative of the target population of the prophylactic indication. Prostate and seminal vesicle concentrations were estimated based on seminal plasma concentrations using a one-step regression method. The exposure to fosfomycin was very similar in rate (Cmax, tmax) after one and two doses. The AUC showed a minimal increment. On average, the apparent volume of distribution was high (>100 L), and the mean clearance had an intermediate value. The total amount and dose fraction of fosfomycin excreted in urine showed a small increment after two doses. The renal clearance was about 5 L/h. The fosfomycin concentration in the prostate and seminal vesicles showed that the antibiotic increased on average after two consecutive doses. This result confirmed the ability of fosfomycin to distribute into the prostate and into seminal vesicles after one single dose and that a two consecutive dose regimen increases the antibiotic availability inside these peripheral tissues.

One-Pot Synthesis of TiO2-rGO Photocatalysts for the Degradation of Groundwater Pollutants.

A non-conventional approach to prepare titanium dioxide-reduced graphene oxide (TiO2-rGO) nanocomposites based on solar photoreduction is here presented. The standard hydro-solvothermal synthesis of the TiO2-rGO composites requires high temperatures and several steps, whereas the proposed one-pot preparation allows one to obtain the photocatalysts with a simple and green procedure, by exploiting the photocatalytic properties of titania activated by the solar irradiation. The TiO2-rGO catalysts were tested in the solar photodegradation of a widely adopted toxic herbicide (2,4-Dichlorophenoxyacetic acid, 2,4-D), obtaining the 97% of degradation after 3 h of irradiation. The as-prepared TiO2-rGO composites were more active compared to the same photocatalysts prepared through the conventional thermal route. The structural, optical, and textural properties of the composites, determined by Raman, Photoluminescence, Fourier Transform InfraRed (FTIR), UV-vis diffuse reflectance (DRS) spectroscopies, and N2 absorption-desorption measurements, showed as the solar irradiation favors the reduction of graphene oxide with higher efficiency compared to the thermal-driven synthesis. Furthermore, the possible toxicity of the as-synthesized composites was measured exposing nauplii of microcrustacean Artemia sp. to solutions containing TiO2-rGO. The good results in the 2,4-D degradation process and the easiness of the TiO2-rGO synthesis allow to consider the proposed approach a promising strategy to obtain performing photocatalysts.

Pharmacokinetics and Safety of Rifamycin SV after Single and Multiple Doses of MMX® Modified Release Tablets in Healthy Male and Female Volunteers.

The primary objective of this single- and multiple-dose pharmacokinetic study was the investigation of rifamycin SV's pharmacokinetic profile in plasma and urine. All the 18 enrolled healthy men and post-menopausal women received modified release tablets containing 600 mg of the oral non-absorbable antibiotic, rifamycin SV, according to a multiple dose regimen: one tablet three times a day (daily intake: 1800 mg) for 14 consecutive days. Blood sampling and urine collection were performed up to 24 h post-dose after the first dose on Days 1 and 7. On average, on Day 1, Cmax,0-24 was 5.79 ± 4.24 ng/mL and was attained in a median time of 9 h. On Day 7, all the subjects had quantifiable levels of rifamycin SV in plasma at each sampling time. After a peak concentration attained 2 h post-dose (mean ± SD concentration: 10.94 ± 16.41 ng/mL), rifamycin SV decreased in plasma to levels similar to those of Day 1. The amounts of rifamycin SV excreted in urine paralleled the plasma concentration at the corresponding times. On Day 1, the total amount excreted in urine was 0.0013%, and was 0.0029% on Day 7. The study results confirmed those of the previous Phase I study: the systemic absorption of rifamycin SV was also proved negligible after 7 days of the 600 mg t.i.d. dose regimen of the newly formulated tablets, currently under development for the treatment of several small and large intestinal pathologies, including diarrhea-predominant irritable bowel syndrome, hepatic encephalopathy, and others. Registered at ClinicalTrials.gov with the identifier NCT02969252, last updated on 26JAN18.

Pharmacokinetics and Safety of Single and Multiple Doses of Oral N-Acetylcysteine in Healthy Chinese and Caucasian Volunteers: An Open-Label, Phase I Clinical Study.

INTRODUCTION: Few studies have evaluated whether the pharmacokinetics of N-acetyl-cysteine (NAC) are different in Chinese and Caucasian individuals. METHODS: This single- and multiple-dose, single-centre, open-label, phase I clinical study was conducted in healthy adult volunteers. All participants received oral NAC 600-mg uncoated tablets, which were administered first as a single dose and, following a 48-h wash-out period, twice daily for 3 days. Blood and urine were collected after single- and multiple-dose NAC administration. Adverse event (AE) data were collected throughout the study. RESULTS: Fifteen Chinese and 15 Caucasian (mostly Italian) individuals (males 66.7%, mean age 36.8 years) participated in the study. Pharmacokinetic characteristics of NAC were similar in the two cohorts. Following both single- and multiple-dose administration, plasma concentration of NAC increased rapidly, reaching a peak at approximately 1.0 h. Maximum plasma concentration and extent of exposure were higher after multiple doses than after a single dose. The accumulation ratio was relatively consistent in both Chinese (mean ± standard deviation 1.5 ± 0.4) and Caucasian (1.4 ± 0.2) participants. The half-life was 15.4 h in Chinese and 18.7 h in Caucasian participants, and the fraction of NAC excreted in urine in the 36 h following administration was 3.7% in Chinese and 3.8% in Caucasian participants. Two Caucasian participants had a total of 3 AEs (headache, presyncope and dysmenorrhoea). No AEs occurred in Chinese participants. CONCLUSIONS: The pharmacokinetic characteristics of NAC are similar in healthy Chinese and Caucasian individuals after single and repeated administration. NAC has a favourable tolerability profile.

Prognostic factors and surgical treatment in vulvar carcinoma: Single center experience.

AIM: Vulvar carcinoma represents 3-5% of all female genital cancers; the main surgical treatment is radical vulvectomy and inguinal lymphadenectomy. The aim of this study is to analyze prognostic factors in the patients underwent to primary surgery for vulvar carcinoma. METHODS: One hundred and eighteen cases of vulvar carcinoma underwent surgery between 2006 and 2016 at Operative Unit of Gynecology and Obstetrics of Cannizzaro Hospital (Catania, Italy) were retrospective analyzed. Risk factors for relapse (age, tumor size, FIGO stage, type of surgery, lymphadenectomy, margins status, metastatic nodes and radiotherapy) were evaluated by logistic regression. Univariate analysis of prognostic factors (age, tumor size, FIGO stage, metastatic inguinal nodes and type of surgery) was obtained by Cox proportional hazard model. Overall survival was calculated by Kaplan-Meier curves either for the entire population and for comparison between positive and negative variables (margin status, nodes and radiotherapy) with log-rank test to determine significance. Statistical significance was reached for P < 0.05. RESULTS: Type of surgery (radical local excision vs. radical vulvectomy) and positive inguinal nodes were identified as risk factors for relapse. Positive inguinal nodes and positive margins were identified as prognostic factors either for overall survival and disease specific survival; tumor size greater than 4 cm was identified as prognostic factors for overall survival. Overall survival was 38.4% and it was significantly higher in the patients with negative margins and nodes. CONCLUSIONS: Nodes status, resection margins, age and type of surgery represent prognostic factors have to be considered for adjuvant treatment in the patients affected from vulvar carcinoma.

The Role of Membrane Capacitance in Cardiac Impulse Conduction: An Optogenetic Study With Non-excitable Cells Coupled to Cardiomyocytes.

Non-excitable cells (NECs) such as cardiac myofibroblasts that are electrotonically coupled to cardiomyocytes affect conduction velocity (θ) by representing a capacitive load (CL: increased membrane to be charged) and a resistive load (RL: partial depolarization of coupled cardiomyocytes). In this study, we untangled the relative contributions of both loading modalities to NEC-dependent arrhythmogenic conduction slowing. Discrimination between CL and RL was achieved by reversibly removing the RL component by light activation of the halorhodopsin-based hyperpolarizing membrane voltage actuator eNpHR3.0-eYFP (enhanced yellow fluorescent protein) expressed in communication-competent fibroblast-like NIH3T3 cells (3T3 HR cells) that served as a model of coupled NECs. Experiments were conducted with strands of neonatal rat ventricular cardiomyocytes coated at increasing densities with 3T3 HR cells. Impulse conduction along preparations stimulated at 2.5 Hz was assessed with multielectrode arrays. The relative density of 3T3 HR cells was determined by dividing the area showing eYFP fluorescence by the area covered with cardiomyocytes [coverage factor (CF)]. Compared to cardiomyocytes, 3T3 HR cells exhibited a depolarized membrane potential (-34 mV) that was shifted to -104 mV during activation of halorhodopsin. Without illumination, 3T3 HR cells slowed θ along the preparations from ∼330 mm/s (control cardiomyocyte strands) to ∼100 mm/s (CF = ∼0.6). Illumination of the preparation increased the electrogram amplitudes and induced partial recovery of θ at CF > 0.3. Computer simulations demonstrated that the θ deficit observed during illumination was attributable in full to the CL represented by coupled 3T3 HR cells with θ showing a power-law relationship to capacitance with an exponent of -0.78 (simulations) and -0.99 (experiments). The relative contribution of CL and RL to conduction slowing changed as a function of CF with CL dominating at CF ≤ ∼0.3, both mechanisms being equally important at CF = ∼0.5, and RL dominating over CL at CF > 0.5. The finding that RL did not affect θ at CFs ≤ 0.3 is explained by the circumstance that, at the respective moderate levels of cardiomyocyte depolarization, supernormal conduction stabilized propagation. The findings provide experimental estimates for the dependence of θ on membrane capacitance in general and suggest that the myocardium can absorb moderate numbers of electrotonically coupled NECs without showing substantial alterations of θ.

Children Learn to Read: How Visual Analysis and Mental Imagery Contribute to the Reading Performances at Different Stages of Reading Acquisition.

Reading in alphabetic orthography requires analysis and recognition of specific attributes of visual stimuli, and generation, reactivation, and use of mental images of letters and words. This study evaluated the role of visual analysis and mental imagery in reading performances of students at different stages of reading acquisition. Reading "comprehension," "accuracy," and "speed," were analyzed. Participants were 90 children who attended primary school. Children were assessed in the first and third grade. The results highlighted that mental imagery and visual analysis influenced reading acquisition. These abilities are differently involved in the three dimensions of reading skill. The issues of this study have practical and educational applications. The early assessment of visual analysis and mental imagery skills and specific training on these abilities could contribute to facilitate reading acquisition. Strategies of intervention centered on visual imagery could increase reading performances in typically developing children and children at risk of learning difficulties.

Ultrasound examination with color power Doppler to assess the early response of apical periodontitis to the endodontic treatment.

OBJECTIVES: The purpose of this study was to assess the possibility to detect early vascular changes in apical periodontitis (AP) using ultrasound examination with color power Doppler (US-CPD) and to establish a correlation between the early response of AP to treatment and its potential healing. MATERIALS AND METHODS: Twenty-one apical lesions were visualized with US-CPD before endodontic treatment, 1 week after the first access to endodontic system and 4 weeks after root canal obturation. A differential diagnosis between cystic lesions (CLs) and granulomatous lesions (GLs) was attempted. The vascular modifications were then correlated with long-term radiographic follow-up using Fisher's exact test. RESULTS: The decrease or disappearance of vascular flow observed in AP 4 weeks after root canal obturation was significantly related to a healing trend (p = 0.0206) of the lesions. Combining the data with preoperative US-CPD diagnosis showed a reproducibility for GLs only (p = 0.0022). CONCLUSIONS: This study showed the possibility to detect early vascular changes in AP using US-CPD, correlating them with a healing trend after endodontic treatment. Future investigations should be conducted and more attention should be dedicated to the potential of this alternative and biologically safe imaging technique. CLINICAL RELEVANCE: US-CPD in endodontics may be a helpful tool to identify healing processes after endodontic treatment and to understand the behavior of different forms of AP.

A 10-year evaluation on adolescents with anxiety disorders: are they at risk of bipolarity?

OBJECTIVE: Anxiety disorders are the most frequent disorders comorbid with bipolar disorder (BD) often preceding the BD onset. The presence of comorbid anxiety in patients diagnosed with BD is associated with worsening of their BD symptoms, increased risky behaviour, decreased response to pharmacological treatment and deterioration in their quality of life and global functioning. The aim of this study was to investigate if anxiety disorders in adolescence could be considered as predictors of BD. METHODS: Adolescents with a primary anxiety disorder were recruited consecutively from the Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin. Subjects were evaluated for Axis I psychiatric disorders, family history and global functioning, and followed up on average 10 years later. RESULTS: A total of 29 patients (59.2%) were male and the mean age at the onset of anxiety disorder was 16.3 (±0.8). Ten years following recruitment, 11 (22.4%) patients fulfilled the criteria for BD. Of them, 10 (90.9%) had a family history of BD and four (36.4%) presented a comorbid substance use disorder. CONCLUSIONS: Our study shows that both family history of BD and substance use disorder, in adolescent patients with a primary anxiety disorder, should be considered as potential predictors of BD onset.

Pharmacokinetics and Pharmacodynamics of Follicle-Stimulating Hormone in Healthy Women Receiving Single and Multiple Doses of Highly Purified Human Menotrophin and Urofollitrophin.

BACKGROUND AND OBJECTIVE: Highly purified human menotrophin and urofollitrophin preparations obtained from human urine via a novel patented purification method have been tested over a timeframe of 14 years in the studies presented in this article. The objective of the studies was to investigate the pharmacokinetics and the pharmacodynamics of follicle-stimulating hormone (FSH) after single subcutaneous and intramuscular doses and multiple subcutaneous doses of the tested preparations in healthy fertile pituitary-suppressed women. DESIGNS: We performed five open, randomised, crossover, single-dose bioequivalence and/or bioavailability studies and one open, multiple-dose, pharmacokinetics and pharmacodynamics study. STUDY SUBJECTS AND TREATMENTS: The six studies included 121 healthy fertile women taking their usual combined oral contraceptives for 3 months before the study: Study 1: 300 international units (IU) of highly purified menotrophin as single subcutaneous and intramuscular doses. Study 2: 300 IU of highly purified menotrophin (test formulation vs. comparator) as single subcutaneous doses. Study 3: 300 IU of highly purified urofollitrophin (hp-FSH) (test formulation vs. comparator) as single subcutaneous doses. Study 4: 300 IU (2 × 150 IU vs. 4 × 75 IU) of hp-FSH as single subcutaneous doses. Study 5: 225 and 445 IU of hp-FSH as single subcutaneous doses. Study 6: daily 225 IU of hp-FSH as subcutaneous doses for 5 consecutive days. MAIN OUTCOME MEASURES: The main outcome measures were the FSH pharmacokinetic parameters, estradiol concentrations, and the number and size of the follicles. RESULTS: FSH after single subcutaneous and intramuscular injections of menotrophin or urofollitrophin attained a systemic peak (maximum) concentration (C max) that was on average consistent throughout the first four studies and ranged from 4.98 to 7.50 IU/L. The area under the plasma concentration-time curve (AUC) from administration to the last observed concentration time t (AUCt) ranged from 409.71 to 486.16 IU/L·h and the elimination half-life (t ½) ranged from 39.02 to 53.63 h. After multiple doses of urofollitrophin (225 IU) for 5 days, FSH attained a mean C max of 14.93 ± 2.92 IU/L and had an AUC during the time interval τ between two consecutive doses at steady state (AUCτ) of 322.59 ± 57.92 IU/L·h, which was similar to the mean AUCt after a single subcutaneous dose of 225 IU of urofollitrophin in study 5 (306.82 ± 68.37 IU/L·h). CONCLUSIONS: In our studies, the intramuscular and subcutaneous routes of menotrophin were equivalent; both menotrophin and urofollitrophin were bioequivalent to their marketed reference; FSH kinetic parameters following injection of urofollitrophin were dose proportional and independent from the administered concentration; and multiple doses of FSH increased estradiol levels and enhanced growth of follicles with a good dose-response correlation. Local tolerability was excellent throughout the six studies.

The Buccal Fat Pad for Closure of Oroantral Communication.

The buccal fat pad (BFP) is a well-established tool in oral and maxillofacial surgery and its use has proved of value for the closure of oroantral communications. Oroantral communication may be a common complication after sequestrectomy in "bisphosphonate-related osteonecrosis of the jaws."The authors report a clinical case of a 70-year-old female patient in bisphosphonate therapy presented with right maxillary sinusitis and oroantral communication after implants insertion.The BFP was used to close the defect. The patient had an uneventful postoperative healing without dehiscence, infection, and necrosis.The authors postulate that the primary closure of the site with BFP may ensure a sufficient blood supply and adequate protection for an effective bone-healing response to occur.

Recombinant filgrastim (BK0023) pharmacodynamics and pharmacokinetics after single and multiple escalating doses in an equivalence study in healthy men.

BACKGROUND AND OBJECTIVES: The new filgrastim formulation, BK0023, whose synthesis method is patented, was tested in a phase I clinical study that was aimed at investigating the pharmacodynamic and pharmacokinetic equivalence and the safety of BK0023 in healthy male subjects. METHODS: Single and multiple escalating doses were administered to healthy male volunteers according to a double-blind, randomised, two-way crossover design. Thirty-two subjects received subcutaneous filgrastim 2.5 µg/kg/day for 7 consecutive days in each period, 36 subjects received 5 µg/kg/day for 7 days in each period, and 22 subjects received 10 µg/kg/day for 5 days. Absolute neutrophil count (ANC) and CD34+ cell count were measured in whole blood as primary and secondary pharmacodynamic parameters. Filgrastim concentrations were measured in serum to calculate the primary pharmacokinetic parameters. RESULTS: The maximum ANC and the area under the curve of the ANC after the first dose and to the end of treatment satisfied the equivalence criterion (95 % confidence intervals within 85-115 or 85-117 % in case of log-transformation). At all three dose regimens, BK0023 was also bioequivalent to the reference product in terms of pharmacokinetic profile of serum filgrastim. The frequency of the treatment-emergent adverse events did not differ significantly between treatments, with the most frequent untoward effects being back and bone pain. CONCLUSIONS: Equivalence could be established using both the baseline-adjusted values and the original unadjusted values. The tested formulation at all three dose regimens was also bioequivalent to the reference product in terms of pharmacokinetic profile.

Laparoscopic Reversal of Hartmann's Procedure: State of the Art 20 Years after the First Reported Case.

Introduction. Aim of the present work is to review the literature to point out the role of laparoscopic reversal of Hartmann procedure. Material and Methods. Number of patients, age, sex, etiology, Hinchey classification, interval between procedure and reversal, position of the first trocars, mean operative time (min), number and causes of conversion, length of stay, mortality, complications, and quality of life were considered. Results. 238 males (52.4%) and 216 females (47.6%) between 38 and 67 years were analyzed. The etiology was diverticulitis in 292 patients (72.1%), carcinoma in 43 patients (10.6%), and other in 70 patients (17.3%). Only 7 articles (22.6%) reported Hinchey classification. The interval between initial procedure and reversal was between 50 and 330 days. The initial trocar was open positioned in 182 patients (43.2%) through umbilical incision, in 177 patients (41.9%) in right upper quadrant, and in 63 patients (14.9%) in colostomy site. The operative time was between 69 and 285 minutes. A total of 83 patients (12.1%) were converted and the causes were reported in 67.4%. The length of stay was between 3 and 12 days. 5 patients (0.7%) died. The complications concern 112 cases (16.4%). Conclusion. The laparoscopic Hartmann's reversal is safer and achieves faster positive results.

Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®.

BACKGROUND: Filgrastim or methionyl-granulocyte colony-stimulating factor (Met-G-CSF), is a recombinant therapeutic protein widely used to treat severe neutropenia caused by myelosuppressive drugs in patients with nonmyeloid malignancies. In addition to its role in the regulation of granulopoiesis, treatment with G-CSF is considered the standard approach to mobilize CD34 positive (CD34+) mononuclear cells for reconstituting hemopoietic ability for bone marrow transplantation. An intended biosimilar filgrastim (coded BK0023) was produced in GMP conditions by E.coli fermentation according to an original recombinant process and showed physico-chemical properties and purity profile similar to Neupogen®, a commercial preparation of filgrastim. The aim of the present study was to demonstrate the comparability of BK0023 to Neupogen® in terms of both in vitro biological activities and in vivo toxicology, pharmacokinetics and pharmacodynamics. METHODS: Cell proliferation and radioligand binding assays were conducted in NFS-60 cells to compare the biological activity and functional interaction with the G-CSF receptor in vitro, while preclinical in vivo studies, including pharmacokinetics and pharmacodynamics after repeated dose were performed in normal and neutropenic rats. A phase I study was carried out in healthy male volunteers treated by multiple-dose subcutaneous administration of BK0023 and Neupogen® to evaluate their pharmacodynamic effects as well as their pharmacokinetic and safety profile and to demonstrate their pharmacodynamic equivalence and pharmacokinetic bioequivalence. RESULTS: The results reported in this work demonstrate that BK0023 is comparable in terms of biological activity, efficacy and safety to Neupogen®. CONCLUSIONS: BK0023 has the same pharmacokinetic profile, efficacy and safety as the reference commercial filgrastim Neupogen® and therefore could be further developed to become a convenient option to treat neutropenia in oncological patients.