High tibial osteotomy in varus knees: indications and limits

Opening wedge high tibial osteotomy (OWHTO) is a surgical procedure that aims to correct the weight-bearing axis of the knee, moving the loads laterally from the medial compartment. Conventional indications for OWHTO are medial compartment osteoarthritis and varus malalignment of the knee; recently OWHTO has been used successfully in the treatment of double and triple varus. OWHTO, in contrast to closing wedge high tibial osteotomy, does not require fibular osteotomy or peroneal nerve dissection, or lead to disruption of the proximal tibiofibular joint and bone stock loss. For these reasons, interest in this procedure has grown in recent years. The aim of this study is to review the literature on OWHTO, considering indications and prognostic factors (body mass index, grade of osteoarthritis, instability, range of movement and age), outcomes at mid-term follow-up, and limits of the procedure (slope modifications, patellar height changes and difficulties in conversion to a total knee arthroplasty)

Virological response and resistance profile in highly treatment-experienced HIV-1-infected patients switching to dolutegravir plus boosted darunavir in clinical practice

Objectives: We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)-experienced HIV-1-infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time. Methods: Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch. Results: Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non-NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG + bDRV. In viraemic patients, the overall probability of VS by 12 months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24 months after therapy start. Patients with previous time under virological suppression ≤ 6 months showed a higher VR probability compared with others (37.5% vs. 6.7%, P < 0.002). Among 13 non-responding patients for whom a genotypic resistance test result at failure was available, only two (15.4%) accumulated further resistance in integrase (Y143C/H/R; S147G and N155H) and protease (V32I, L33F, I54L). Conclusions: In highly treatment-experienced patients, the use of dual therapy based on DTG + bDRV appears to be a very good regimen for switch therapy, with a high rate of virological control in both viraemic and virologically suppressed patients. Among non-responding patients, the selection of further resistance is a rare event

Anti-cancer activity of dose-fractioned mPE +/- bevacizumab regimen is paralleled by immune-modulation in advanced squamous NSLC patients

Background: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology. Methods: Retrospective analysis was carried out in a subset of 31 patients with squamous histology enrolled in the study between September 2007 and September 2015. All of the patients received chemotherapy with cisplatin (30 mg/sqm, days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE) and 14 of them also received bevacizumab 5 mg/kg on the day 3q21 (mPEBev regimen). Results: This treatment showed a disease control rate of 71% with a mean progression free survival (PFS) and overall survival (OS) of 13.6 and 17 months respectively. After 4 treatment courses, 6 patients showing a remarkable tumor shrinkage, underwent to radical surgery, attaining a significant advantage in term of survival (P=0.048). Kaplan-Meier and log-rank test identified the longest survival in patients presenting low baseline levels in neutrophil-to-lymphocyte ratio (NLR) (P=0.05), interleukin (IL) 17A (P=0.036), regulatory-T-cells (Tregs) (P=0.020), and activated CD83+ dendritic cells (DCs) (P=0.03). Conclusions: These results suggest that the mPE +/- bevacizumab regimen is feasible and should be tested in comparative trials in advanced squamous-NSCLC (sqNSCLC). Moreover, its immune-biological effects strongly suggest the investigation in sequential combinations with immune check-point inhibitors

Splenic trauma : WSES classification and guidelines for adult and pediatric patients

Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be different, children should always be treated in dedicated pediatric trauma centers. In fact, the vast majority of pediatric patients with blunt splenic trauma can be managed non-operatively. This paper presents the World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines.Peer reviewe

The open abdomen in trauma and non-trauma patients : WSES guidelines

Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a "planned second-look" laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-trauma patients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuries or critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consuming and represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only be considered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as the patient can physiologically tolerate it. All precautions to minimize complications should be implemented.Peer reviewe

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies