BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

Age-Related Variations of Muscle Mass,Strength, and Physical Performance in Community-Dwellers: Results From the Milan EXPO Survey

Objectives

Declining muscle mass and function are hallmarks of the aging process. The preservation of muscle trophism may protect against various negative health outcomes. Age- and sex-specific curves of muscle mass, strength, and function, using data from a large sample of community-dwelling people, are necessary.

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Nutritional Status after Roux-En-Y (Rygb) and One Anastomosis Gastric Bypass (Oagb) at 6-Month Follow-Up: A Comparative Study

Introduction: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are two effective bariatric surgical procedures with positive outcomes in terms of weight loss, comorbidities remission, and adverse events profiles. OAGB seems to carry a higher risk of malnutrition, but existing data are controversial. The aim of this study is to objectively evaluate and compare malnutrition in patients undergoing RYGB and OAGB. Methods: Retrospective monocentric study of obese patients undergoing RYGB or OAGB between the 15 September 2020 and the 31 May 2021. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score and compared between groups. The primary outcome was the mean CONUT score at 6 months. The secondary outcomes included the incidence of malnutrition, comorbidities, including hypertension, insulin resistance and type II diabetes mellitus, and weight loss. Results: 78 patients were included: 30 underwent RYGB and 48 underwent OAGB. At 6-Month Follow-Up there was no difference between groups in the mean CONUT score nor in incidence of malnutrition. In both groups, the nutritional status significantly worsened 6 months after surgery (preoperative and postoperative score of 0.48 ± 0.9 and 1.38 ± 1.5; p = 0.0066 for RYGB and of 0.86 ± 1.5 and 1.45 ± 1.3; p = 0.0422 for OAGB). Type II Diabetes mellitus (DMII) and hypertension remission were significant in the OAGB group with a 100% relative remission in the DMII-OAGB group (p = 0.0265), and a 67% relative remission in the hypertension-OAGB group (p = 0.0031). Conclusions: No difference in nutritional status has been detected between patients undergoing RYGB or OAGB at the 6-Month Follow-Up. Both procedures may have significant mal-absorptive effects leading to decline in nutritional status. OAGB may be more efficacious in inducing DMII and hypertension remission. Larger prospective studies dedicated specifically to nutritional status after gastric bypass are needed to confirm the impact of different bypass procedures on nutritional status.     

Quantitative real time PCR assays for the detection of Leishmania (Viannia) braziliensis in animals and humans

American cutaneous leishmaniasis (ACL) caused by Leishmania (Viannia) braziliensis is a neglected disease of humans in the New World that may also cause irreversible skin and eventually mucocutaneous lesions. This parasite can also infect dogs and represents a diagnostic challenge for veterinarians. Methods currently available for the diagnosis of ACL have a low sensitivity and may be time-consuming, representing a limit for treatment expedition of ACL. Quantitative real time PCR assays (qPCR) for the detection of L. (V.) braziliensis in canine blood samples were developed herein, and the detection limit and specificity of different molecular targets (kDNA and rDNA) evaluated. Of the protocols assessed, two qPCR assays, one targeting the kDNA and other the SSU rDNA of L. (V.) braziliensis, performed better, with detection limits of 100 fg and 10 pg, respectively. These assays were also used to test skin samples from humans with suspected ACL. The results indicate that the qPCR protocols developed represent an advance for the diagnosis of ACL in dogs and humans from this region, and provide a rapid and non-invasive diagnosis of the infection by L. (V.) braziliensis. Considering the quantitative nature of the assays, they will also be useful for monitoring treatment efficacy and preventing relapses in human patients in Brazil, although further studies are needed to critically evaluate the specificity of the qPCRs for their capacity to distinguish different Leishmania species and subspecies (represented by zymodemes) in other countries. Finally, molecular assays established may represent new tools for future basic and applied research focused on species identification, host–parasite associations, and infection dynamics in host and vector populations.     

Neural coding of nociceptive stimuli—from rat spinal neurones to human perception

Translational studies are key to furthering our understanding of nociceptive signalling and bridging the gaps between molecules and pathways to the patients. This requires use of appropriate preclinical models that accurately depict outcome measures used in humans. Whereas behavioural animal studies classically involve reports related to nociceptive thresholds of, for example, withdrawal, electrophysiological recordings of spinal neurones that receive convergent input from primary afferents permits investigation of suprathreshold events and exploration of the full-range coding of different stimuli. We explored the central processing of nociceptive inputs in a novel parallel investigation between rats and humans. Using radiant laser pulses, we first compared the electrophysiological responses of deep wide dynamic range and superficial nociceptive-specific neurones in the rat dorsal horn with human psychophysics and cortical responses. Secondly, we explored the effects of spatial summation using laser pulses of identical energy and different size. We observed 3 main findings. Firstly, both rodent and human data confirmed that neodymium–yttrium aluminium perovskite laser stimulation is a nociceptive-selective stimulus that never activates Aβ afferents. Secondly, graded laser stimulation elicited similarly graded electrophysiological and behavioural responses in both species. Thirdly, there was a significant degree of spatial summation of laser nociceptive input. The remarkable similarity in rodent and human coding indicates that responses of rat dorsal horn neurones can translate to human nociceptive processing. These findings suggest that recordings of spinal neuronal activity elicited by laser stimuli could be a valuable predictive measure of human pain perception.     

Laparoscopic appendectomy for acute and recurrent appendicitis: retrospective analysis of a single-group 5-year experience

BACKGROUND AND PURPOSE: Twenty years after the first report of laparoscopic appendectomy (LA), its role in the treatment of appendicitis is still under debate. We report herein a retrospective analysis of our cases of LA in the last 5 years, during which we adopted a policy of an almost uniform laparoscopic approach on a rather selected population composed mainly of women with acute or recurrent lower quadrant abdominal pain. PATIENTS AND METHODS: Laparoscopic appendectomy was performed on 33 male and 98 female patients. The mean age at operation was 25.7+/-11.4 years (range 11-59 years). Acute appendicitis with localized or diffuse peritonitis was present in 34 cases. In the remaining 97 patients, the operation was performed for acute or recurring symptoms of lower quadrant abdominal pain. RESULTS: There were no conversions to open surgery. The operating time was 45+/-17 minutes (range 30-110 minutes). The pathology examination of the removed appendices showed acute appendicitis in 34 cases and chronic inflammation in the remaining 97 patients. In one case, histology revealed a coexisting mucinous carcinoid that extended to the perivisceral fat, and a completion right hemicolectomy was performed. Complications were minor in most cases. Reoperation for deep abdominal abscess or hematoma was required in three cases. The mean hospital stay was 2.59+/-1.58 days (range 24 hours-11 days). CONCLUSION: In our hands, LA has proven to be safe and effective. The laparoscopic operation has significant advantages in terms of lower invasiveness and better diagnostic capability. It is especially useful in women of child-bearing age, in whom it may be considered the procedure of choice.     

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.     

Determinants of surgical morbidity in gastric cancer treatment

BACKGROUND: The occurrence of early surgical complications after gastrectomy as a treatment for gastric cancer has been reported to have a negative impact on longterm survival. The aim of this study was to identify treatment-related factors that can predict morbidity and mortality in patients undergoing operations for gastric cancer. STUDY DESIGN: The charts of 388 patients who underwent different operations for gastric cancer at A Gemelli General Hospital, Catholic University of Rome, Italy, between January 1992 and April 2007, were reviewed. Patients were grouped according to the type of surgical treatment performed. The study end points were postoperative morbidity, mortality, and the length of hospital stay after surgery. RESULTS: Overall morbidity and mortality rates were 16.2% (63 patients) and 2.3% (9 patients), respectively. Overall morbidity rates were higher in patients more than 64 years of age, when a gastric tumor was resected along with the spleen, and when an extended lymphadenectomy was performed. Patients older than 64 years had longer postoperative hospital stays, and Roux-en-Y gastrojejunostomy was predictive of a shorter stay. Mortality was not influenced by any surgically related factors. CONCLUSIONS: Age, splenectomy, and extended lymphadenectomy were independently associated with the development of complications after gastric cancer operations. After subtotal gastrectomy, Roux-en-Y gastrojejunostomy was associated with a shorter postoperative length of stay than conventional Billroth I and Billroth II reconstructions.     

Seven-year performance of the Edwards Prima Plus stentless valve with the intact non-coronary sinus technique

OBJECTIVES: Late results after stentless aortic valve replacement (AVR) may be jeopardized by progressive aortic dilatation. To define functional outcome using the intact non-coronary sinus technique, all patients operated using the stentless Edwards Prima Plus xenograft were assessed. METHODS: Between January 2000 and August 2007, 154 patients, aged 71 +/- 9 years, underwent stentless AVR using a technique, which replaces the non-coronary sinus and stabilizes two of three commissures. Indication was aortic valve stenosis (AS) in 103 (67%) patients: 33 (21%) had bicuspid valve and four endocarditis. Ninety-six (62%) patients were in NYHA III-IV, and 13 (8%) had LVEF <30%. Associated procedures were required in 59 (38%) patients (CABG, 34; ascending aorta, 22; others 3). Study endpoints were survival, freedom from valve-related events, clinical status, and graft function. RESULTS: There were two hospital and two late deaths during a 48 +/- 19 months (1-92) follow-up (97 +/- 3% survival at seven years). Seven-year freedom from structural failure, nonstructural failure, and endocarditis was 99 +/- 1%, 97 +/- 3%, and 98 +/- 2%. Follow-up NYHA (96 vs ten patients in class III-IV, p = 0.001), and cardiac function (13 vs one patient with LVEF <30%, p = 0.02) were improved. Xenograft performance was satisfactory: 0-2 + aortic insufficiency (AI) in 147 (98%) patients, mean trans-prosthetic pressure gradient 8 +/- 4 (0-25 mmHg). Aortic root diameters were comparable to postoperative values (sinus of Valsalva, 36 +/- 8 vs 35 +/- 9 mm, p = ns; sinotubular junction, 32 +/- 7 vs 34 +/- 8 mm, p = ns). CONCLUSIONS: Stentless AVR with non-coronary sinus replacement affords excellent late outcome and low rate of valve-related events, even in complex patients (bicuspid valve, LV failure, and endocarditis). Aortic root dimensions remain stable over time allowing rewarding xenograft function.