HIV cure: global overview of bNAbs’ patents and related scientific publications

Introduction: This article provides a global overview of patent deposits for broadly neutralizing antibodies (bNAbs), which have emerged as a key strategy for HIV cure and future HIV vaccines. Scientific and technological barriers to the discovery of an effective HIV vaccine in the last 40 years have raised concerns on the potential for relevant advances in this area. Nevertheless, recent breakthrough studies have identified novel immune pathways for new innovative HIV vaccine and HIV cure strategies.

Areas covered: In our patent study, we have identified in a global scale, in the last decade, a sharp increase in the number of bNAbs’ patent deposits related to HIV prevention and treatment strategies, reaching 90 bNAbs in 2017, protected by 184 different patent deposits. Refining our patent search to the different stages of bNAbs’ development has also allowed us to identify 12 of them already at clinical stage of research (VRC01, 10E8, 3BNC117, 10-1074, 2G12, 2F5, KD-247, 4E10, PG9, PGDM1400, PGT121, and VRC07). We describe these recent breakthroughs and discuss the prospects and limitations of these novel strategies.

Expert opinion: Our results indicate the intellectual property outcomes of a scientific revolution in this field, expressing innovative modifications in antibodies to increase their potency and half-life, which have resulted in extremely potent antibodies that could provide novel preventive and therapeutic HIV strategies.     

Incidence and Risk Factors for Hepatitis C Virus Infection among Illicit Drug Users in Italy

So far, only three small outdated studies have investigated hepatitis C virus (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus, during 2007–2010, we conducted a prospective cohort study among DUs attending 17 Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV-uninfected DUs were prospectively followed by interview and anti-HCV antibody and RNA testing every 6 months. Incidence was calculated using the person-years method. Infection predictors were assessed by time-dependent Cox analysis. Participants were mostly male (83.4%), under opioid substitution therapy (OST) (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of 224 DUs initially under OST interrupted treatment during the follow-up. Overall HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals (CI), 3.63–9.38]. The incidence did not significantly differ according the participants’ sociodemographic characteristics or the degree of urbanization of the towns involved in the study. The incidence was higher for DUs under than for those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p = 0.55). However, all these differences were non-significant. At last follow-up visit, a significant decrease in frequency of sharing equipment for preparation/using drugs (by injection or not) was observed by analyzing either the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted independently associated with sharing drug preparation/use equipment, backloading, having a HCV-positive sexual partner, or household and (marginally) intravenous injection. In this study, HCV incidence was non-negligible and OST seemed to lack effectiveness in reducing it. In Italy, implementation of combined harm reduction interventions and antiviral treatment of chronically infected DUs would be needed.     

Simple bone cyst: possible misdiagnosis in periapical pathology

Simple bone cysts are non-neoplastic bone lesions, classified as intraosseous pseudocysts without epithelial lining, that can be empty or filled by fluid and display uncommon clinical and radiographic features. This article presents an unusual case of a simple bone cyst with clinical and radiographic features similar to chronic apical periodontitis. A general dentist referred an 18-year-old man for endodontic treatment after the patient complained of pain in the mandibular right second molar, which displayed a significant bony radiolucency. Chronic periapical lesion was excluded after detailed clinical and radiographic examinations. During surgical exploration, an empty bone cavity was observed and curetted before wound closure. One year later, complete healing was observed.     

Results obtained with level II oncoplastic surgery spanning 20 years of breast cancer treatment: Do we really need further demonstration of reliability?

Oncoplastic surgery (OPS) has demonstrated its superiority above traditional breast conserving surgery, but is still struggling to consolidate its role in breast cancer therapeutic protocols mainly because of contrasting scientific evidences and reduced follow‐up results available. The objective of our contribution is to analyze results obtained with 381 patients consecutively treated in our Multidisciplinary Breast Center by means of level II OPS between January 1998 and January 2018 for unilateral, primary breast cancer. Surgical endpoints were mean specimen weight and volume, mean diameter of main lesion (MLD), rates of positive margins (PMR), re‐excision (RR), conversion to mastectomy (CMR), complications (CR) and oncological endpoints as overall survival (OS), disease‐free survival (DFS), and local recurrence rate (LR). About 29.1% were treated for multifocal/multicentric disease, and 29.1% previously underwent neo‐adjuvant chemotherapy (NACT). Regarding surgical techniques, 53.0% of patients received “inverted T” and 30.1% “J” mammoplasties, whereas 13.6% underwent “round block,” 2.3% “Grisotti,” and 1% “batwing” techniques. Regarding surgical outcomes, mean specimen weight was 215 g (50‐2157) and volume 345 mm³ (21‐7980). MLD 23 mm, PMR 7.6%, RR 3.6%, CMR 1.6%, and CR 5.8%. With a mean follow‐up of 118 months, oncological outcomes were: OS 93.7%, DFS 82.3%, LR 4.4%. In conclusion, our analysis confirmed level II OPS reliability even for longer follow‐up timing and in difficult situations as multifocal disease or after NACT.     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

A multidisciplinary rehabilitation programme improves disability,kinesiophobia and walking ability in subjects with chronic low back pain: results of a randomised controlled pilot study

Purpose

To evaluate the effect of a multidisciplinary rehabilitation programme on disability, kinesiophobia, catastrophizing, pain, quality of life and gait disturbances in patients with chronic low back pain (CLBP).

Methods

This was a parallel-group, randomised, superiority-controlled pilot study in which 20 patients were randomly assigned to a programme consisting of motor training (spinal stabilising exercises plus usual-care) and cognitive–behavioural therapy (experimental group, 10 subjects) or usual-care alone (control group, 10 subjects). Before treatment, 8 weeks later (post-treatment), and 3 months after the end of treatment, the Oswestry Disability Index, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, a pain numerical rating scale, and the Short-Form Health Survey were assessed. Spatio-temporal gait parameters were also measured by means of an electronic walking mat. A linear mixed model for repeated measures was used for each outcome measure.

Results

The programme had significant group (p = 0.027), time (p < 0.001), and time-by-group interaction (p < 0.001) effects on disability, with the experimental group showing an improvement after training of about 61 % (25 % in the control group). The analyses of kinesiophobia, catastrophizing, and the quality of life also revealed significant time, group, and time-by-group interaction effects in favour of the experimental group, and there was a significant effect of time on pain. Both groups showed a general improvement in gait parameters, with the experimental group increasing cadence significantly more.

Conclusion

The multidisciplinary rehabilitation programme including cognitive–behavioural therapy was superior to the exercise programme in reducing disability, kinesiophobia, catastrophizing, and enhancing the quality of life and gait cadence of patients with CLBP.     

Management of Facial Nerve in Surgical Treatment of Previously Untreated Fisch Class C Tympanojugular Paragangliomas: Long-Term Results

The aim of this study was to evaluate the long-term facial nerve outcome according to management of the facial nerve in patients undergoing surgery for Fisch class C tympanojugular paragangliomas. The study population consisted of 122 patients. The infratemporal type A approach was the most common surgical procedure. The facial nerve was left in place in 2 (1.6%) of the 122 patients, anteriorly rerouted in 97 (79.5%), anteriorly rerouted with segmental resection of the epineurium in 7 (5.7%), and sacrificed and reconstructed in 15 (12.3%). One patient underwent cross-face nerve grafting. At last follow-up, House-Brackmann grade I to II was achieved in 51.5% of patients who underwent anterior rerouting and in 28.5% of those who underwent anterior rerouting with resection of the epineurium. A House-Brackmann grade III was achieved in 73.3% of patients who underwent cable nerve graft interposition. The two patients in whom the facial nerve was left in place experienced grade I and grade III, respectively. The patient who underwent cross-face nerve grafting had grade III. Gross total resection was achieved in 105 cases (86%). Management of the facial nerve in tympanojugular paraganglioma surgery can be expected to ensure satisfactory facial function long-term outcome.     

Microleakage Analysis of Different Bulk-Filling Techniques for Class II Restorations: µ-CT,SEM and EDS Evaluations

This study aimed to compare two different bulk-filling techniques, evaluating the internal and external adaptation of class II resin-composite restorations, by analysing the gap formation using microcomputed tomography (µ-CT) and scanning electronic microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS). Two standardized mesio/disto-occlusal (MO/DO) cavities were prepared in eight extracted human third molars that were divided, according to the filling technique used, in the following two groups (n = 4): BG (Bulk&Go group) and BT (Bulk Traditional group). After universal bonding application, followed by the light curing, all teeth were restored using a bulk-fill composite. Specimens were scanned with µ-CT to evaluate 3D interfacial gaps. Acquired µ-CT data were analysed to quantify the gap formation. Complementary information to the µ-CT analysis were obtained by SEM. Thereafter, the chemical composition of tooth–restoration interface was analysed using EDS. The µ-CT analysis revealed gaps formation at the tooth–restoration interface for both the BG and BT groups, while within the restoration, only in the BT group there was evidence of microleakage formation. The scanning electron micrographs of both groups showed that the external marginal integrity of the restoration was preserved, while EDS showed the three different structures (tooth surface, adhesive layer and resin composite) of the tooth–restoration interface, highlighting the absence of gap formation. In both BG and BT, the two filling techniques did not show significant differences regarding the internal and external marginal adaptation of the restoration. To achieve a successful restoration, the clinician could be advised to restore a class II cavity using a single increment bulk-filling technique (BG), thus treating it as a class I cavity.