Medium-Long-Term Radiographic and Clinical Outcomes after Surgical Treatment of Intra-Articular Tibial Pilon Fractures by Three Different Techniques

The goal of this retrospective, observational, case series study was to evaluate the medium-long-term clinical and radiographic results of the three most common surgical osteosynthesis techniques used for the treatment of articular tibial pilon fractures: ORIF, MIPO, and EF. Materials and Methods. A consecutive series of patients with articular pilon fractures who underwent surgery at our institution were enrolled in this study. Fractures were classified according to the M\ufcller AO classification system. Overall outcomes took the following into account: radiographic quality of reduction, evaluated using Ovadia and Beals\u2019 criteria; clinical assessment, evaluated using the AOFAS questionnaire; and general health, evaluated with the SF36-v2 Health Survey. Results. A total of 94 articular pilon fractures (34 type 43-B and 60 43-C) were evaluated with a mean follow-up of 56.34 months (range 33\u2013101). The techniques used were ORIF, MIPO, and EF in 63 (67%), 17 (18.9%), and 14 cases (14.1%), respectively. According to Ovadia and Beals\u2019 criteria, good, fair, and poor results were reported in 61 (64.89%), 26 (27.66%), and 7 (7.45%) cases, respectively. The mean AOFAS score was 82.41 for MIPO, 79.83 for ORIF, and 50.57 for EF, respectively. Thirty-nine patients (41.49%) presented early and/or late complications. Conclusion. Satisfactory outcomes using the three different techniques were reported. In particular, the radiographic outcomes were inversely proportional to the fracture comminutions and statistically different between internal and external osteosynthesis, but comparable between ORIF and MIPO techniques. On the other hand, the clinical outcomes were closely related to the soft tissue conditions and the anatomical reconstruction of the joint

Population Pharmacokinetic and Pharmacodynamic Analysis for Maximizing the Effectiveness of Ceftobiprole in the Treatment of Severe Methicillin-Resistant Staphylococcal Infections

Ceftobiprole is a fifth-generation cephalosporin used for different Gram-positive bacterial infections. A population pharmacokinetic analysis was conducted in real-life clinical patients to assess the adequacy of current dosages. Population pharmacokinetics was conducted using non-linear mixed effect modeling. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) of free trough or steady-state concentration over MIC (fCtrough/MIC or fCss/MIC) >= 1 or >= 4 associated with both the standard and intensified dosing regimens adjusted for renal function. Cumulative fraction of response (CFR) against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were also calculated. A total of 132 patients with 503 concentrations were included. Most of them (107/132, 81.1%) had hospital- or community-acquired pneumonia, endocarditis, and bacteremia. A three-compartment model adequately fitted ceftobiprole concentration-time data. Estimated glomerular filtration rate significantly affected drug clearance. Monte Carlo simulations showed that the optimal target of fCtrough/MIC or fCss/MIC >= 4 is achieved only with the use of the standard dosages administered by continuous infusion (CI) against MRSA infections in patients with preserved renal function. Intensified dosages administered by CI are needed in patients with impaired renal function and/or augmented renal clearance against MRSA and in patients with preserved renal functions against MRSE

An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking

Response to multiple microenvironmental cues and resilience to mechanical stress are essential features of trafficking leukocytes. Here, we describe unexpected role of titin (TTN), the largest protein encoded by the human genome, in the regulation of mechanisms of lymphocyte trafficking. Human T and B lymphocytes express five TTN isoforms, exhibiting cell-specific expression, distinct localization to plasma membrane microdomains, and different distribution to cytosolic versus nuclear compartments. In T lymphocytes, the LTTN1 isoform governs the morphogenesis of plasma membrane microvilli independently of ERM protein phosphorylation status, thus allowing selectin-mediated capturing and rolling adhesions. Likewise, LTTN1 controls chemokine-triggered integrin activation. Accordingly, LTTN1 mediates rho and rap small GTPases activation, but not actin polymerization. In contrast, chemotaxis is facilitated by LTTN1 degradation. Finally, LTTN1 controls resilience to passive cell deformation and ensures T lymphocyte survival in the blood stream. LTTN1 is, thus, a critical and versatile housekeeping regulator of T lymphocyte trafficking

Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES). a multicentre, open-label, randomised trial

Background: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. Methods: We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365. Findings: Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. Interpretation: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. Funding: Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy

Aromatic substitution by free benzyl cations from the nuclear decay of multi-tritiated toluene. Competitive benzylation of benzene and toluene in the gas phase and in solution.

Benzyl cations, free of counter ions, have been generated from the nuclear decay of tritium atoms contained exclusively in the side-chain of multi-labelled toluene and allowed to react in competition experiments with benzene and toluene. The aromatic substitution was studied in both the gaseous and liquid phase, employing pure aromatics or aromatics dissolved in n-hexane, carbon tetrachloride and nitromethane as the reaction medium. In the gaseous systems, at 20 Torr total pressure, High meta substitution of toluene indicates extensive isomerization of the excited intermediates, while the increase of the kT/kB value in the Presence of NH3 suggests that selective transalkylation competes with proton transfer to ammonia from the benzyl cation adducts with benzene, but not with toluene. High positional and low substrate selectivities were measured in solution, the decrease in kT/kB (from 2·8 to 1·7) in the different solvents being accompanied by an increase in the o/2p ratio. Competition experiments between benzene and methanol indicate that the reaction is not diffusion controlled. The influence of the reaction medium on the substrate selectivity is explained by postulating the formation of a cation–solvent adduct, where the solvent molecule undergoes displacement by the substrate. Positional selectivity would be controlled in a subsequent step

Laparo-endoscopic single site cholecystectomy versus standard laparoscopic cholecystectomy: Results of a pilot randomized trial

BACKGROUND: In recent years, new devices providing multiple channels have made the performance of laparoscopic cholecystectomy through a single access site not only feasible but much easier. The potential benefits of laparoendoscopic single-site (LESS) cholecystectomy may include scarless surgery, reduced postoperative pain, reduced postoperative length of stay, and improved postoperative quality of life. There are no comparative data between LESS cholecystectomy and standard laparoscopic cholecystectomy (LC) available at present with which to quantify these benefits. METHODS: This study was a prospective, randomized, dual-institutional pilot trial comparing LESS cholecystectomy with standard LC. The primary end point was postoperative quality of life, measured as length of hospital stay, postoperative pain, cosmetic results, and SF-36 questionnaire scores. Secondary end points included operative time, conversion to standard LC, difficulty of exposure, difficulty of dissection, and complication rate. RESULTS: No significant differences in postoperative lengths of stay were found in the two groups. Postoperative pain evaluation using a visual analogue scale showed significantly better outcomes in the standard LC arm on the same day of surgery (P = .041). No differences in postoperative pain were found at the next visual analogue scale evaluation or in the postoperative administration of pain-relieving medications. Cosmetic satisfaction was significantly higher in the LESS group at 1-month follow-up (mean, 94.5 ± 9.4% vs 86 ± 22.3%; median, 100% vs 90%; P = .025). Among the 8 scales of the SF-36 assessing patients' physical and mental health, scores on the Role Emotional scale were significantly better in the LESS group (mean, 80.05 ± 29.42 vs 68.33 ± 25.31; median, 100 vs 66.67; P < .0001). CONCLUSIONS: In this pilot trial, LESS cholecystectomy resulted in similar lengths of stay and improved cosmetic results and SF-36 Role Emotional scores but performed less well on pain immediately after surgery. A larger multicenter trial is needed to confirm and further investigate these results

Laparo-endoscopic single site cholecystectomy versus standard laparoscopic cholecystectomy: Results of a pilot randomized trial

BACKGROUND: In recent years, new devices providing multiple channels have made the performance of laparoscopic cholecystectomy through a single access site not only feasible but much easier. The potential benefits of laparoendoscopic single-site (LESS) cholecystectomy may include scarless surgery, reduced postoperative pain, reduced postoperative length of stay, and improved postoperative quality of life. There are no comparative data between LESS cholecystectomy and standard laparoscopic cholecystectomy (LC) available at present with which to quantify these benefits. METHODS: This study was a prospective, randomized, dual-institutional pilot trial comparing LESS cholecystectomy with standard LC. The primary end point was postoperative quality of life, measured as length of hospital stay, postoperative pain, cosmetic results, and SF-36 questionnaire scores. Secondary end points included operative time, conversion to standard LC, difficulty of exposure, difficulty of dissection, and complication rate. RESULTS: No significant differences in postoperative lengths of stay were found in the two groups. Postoperative pain evaluation using a visual analogue scale showed significantly better outcomes in the standard LC arm on the same day of surgery (P = .041). No differences in postoperative pain were found at the next visual analogue scale evaluation or in the postoperative administration of pain-relieving medications. Cosmetic satisfaction was significantly higher in the LESS group at 1-month follow-up (mean, 94.5 ± 9.4% vs 86 ± 22.3%; median, 100% vs 90%; P = .025). Among the 8 scales of the SF-36 assessing patients' physical and mental health, scores on the Role Emotional scale were significantly better in the LESS group (mean, 80.05 ± 29.42 vs 68.33 ± 25.31; median, 100 vs 66.67; P < .0001). CONCLUSIONS: In this pilot trial, LESS cholecystectomy resulted in similar lengths of stay and improved cosmetic results and SF-36 Role Emotional scores but performed less well on pain immediately after surgery. A larger multicenter trial is needed to confirm and further investigate these results

Laparoscopic total gastrectomy in gastric cancer: Our experience in 92 cases

INTRODUCTION: Laparoscopic total gastrectomy (LTG) is seldom used for gastric cancer because the complex vascularization and lymphatic drainage makes lymphadenectomy and esophagojejunal anastomosis difficult and requires special skills. Our aim was to demonstrate the feasibility and accuracy of LTG in gastric cancer with D2 lymphadenectomy. MATERIAL AND METHODS: Eighty-eight LTG and four laparoscopic remnant gastrectomies (LRGs) were performed over >12 years. The median patient age was 64 years, and the male/female ratio was 1.49/1. Eighty-seven patients had a D2 and only five patients had a D1 lymphadenectomy. We propose the retrospective analysis of intra- and perioperative mortality and morbidity. RESULTS: In only four of 96 cases approached by laparoscopy, a conversion to laparotomy was needed. There were two (2.17%) perioperative deaths in 92 procedures and few complications. Histological data show 79 advanced gastric cancers (AGC), 11 early gastric cancers (EGC), and two gastric diffused lymphomas. The five-year Kaplan-Meier overall survival in patients with EGC and AGC was 100% and 58%, respectively. CONCLUSIONS: The results demonstrate the feasibility of an oncologically correct minimally invasive total gastrectomy. We would like to promote comparisons among different institutions to achieve better standardization of indications and techniques for a laparoscopic approach to gastric cancer