Clinical Anatomy of the Ligament of the Head of Femur

The ligament of the head of femur (LHF) has gained clinical attention recently and is reported to contribute to hip stability. This study explores its morphology and morphometry, information that may help inform surgical decision making. Gross anatomical dissections were undertaken on 229 embalmed hips from European (n = 105) and Thai (n = 124) adult cadavers to examine LHF anatomy. Ligament morphometry was statistically compared at different sites, between sexes and sides. The origin of ligamental arteries and absence of the ligament were documented. The LHF was pyramidal or quadrangular in shape. Sub‐synovial fibrous bands originated from the transverse acetabular ligament, edges of the acetabular notch, and acetabular floor; less frequently from the hip joint capsule. Distally, the ligament flattened and converged onto the fovea capitis. The ligament was 22.3 ± 4.4 mm long and was significantly wider (P = 0.001) and thicker (P = 0.0003) at the fovea, compared to its mid‐zone. Branches of the obturator artery entered the acetabular foramen inferomedially and penetrated the middle third of the LHF. Blood vessels ran within the LHF and appeared to enter the fovea. The ligament was absent in 2.8% of Thai hips and there were no significant sex or side differences in ligament dimensions. The morphology of the LHF is complex. While individual variation was apparent, blood vessels were seen in the distal ligament. Precise information on LHF morphometry and attachment sites will help inform appropriate graft dimensions and choice of fixation sites necessary for ligament reconstruction. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.     

Airway pressure release ventilation for in-vivo donor lung management and lung transplant outcomes

Background:Airway pressure release ventilation (APRV) can be used for cadaveric donor lung recruitment. APRV elevates PaO₂ in donor lungs; however, reported outcomes in recipients with APRV-managed donor lungs are limited. Methods:We retrospectively reviewed patients who underwent lung transplantation (LTx) from 2012 to 2013 and divided them into two groups based on mode of ventilation used during donor management and organ extraction (A: non-APRV; B: APRV). Kaplan-Meier method and multivariate Cox regression were used for analysis. Results:We found 126 LTx recipients (LTxRs); 9 were excluded for use of portable ventilation perfusion systems. Of the remaining 117 patients, 81 (69%) were in Group A; 36 (31%) were in Group B. Preoperative LTxR characteristics (age, sex, lung allocation score, end-stage lung disease type) were comparable between groups. Donors for Group B were older (P=0.03) and had higher body mass index (BMI) (P<0.001), higher incidence of death from chest trauma (P=0.008), longer ventilation duration after brain death (P<0.001), and higher pre-explant PaO₂/FiO₂ ratios (P<0.001). Post-LTx duration of mechanical ventilation, hospital stay, and median survival were similar in both groups. Risk of death was comparable between the two groups at the end of follow-up (HR =1.42; 95% CI: 0.57-3.56; P=0.45). Conclusions:APRV is a safe and effective pre-LTx donor lung management strategy. Short- and long-term survival outcomes were comparable in LTx recipients, irrespective of donor ventilation mode. APRV may help recruit lungs from older donors with higher BMI who die from chest trauma and have anticipated longer ventilation duration.     

Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies

Background Arginine depletion interferes with pyrimidine metabolism and DNA damage-repair pathways, and pairing arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG20) with platinum enhances cytotoxicity in vitro and in vivo in arginine auxotrophs.Methods This single-centre, Phase 1 trial was conducted using a 3 + 3 dose escalation designed to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of ADI-PEG20.Results We enrolled 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies. We observed no dose-limiting toxic effects or treatment-related mortality. Three percent of patients discontinued treatment because of toxicity. After treatment, 5% (5/99) of patients had partial responses, and 41% had stable disease. The median progression-free and overall survival durations were 3.62 and 8.06 months, respectively. Substantial arginine depletion and citrulline escalation persisted in most patients through weeks 24 and 8, respectively. Tumour responses were associated with anti-ADI-PEG20 antibody levels at weeks 8 and 16 (p = 0.031 and p = 0.0357, respectively).Conclusion Concurrently administered ADI-PEG20 and cisplatin had an acceptable safety profile and had shown antitumour activity against metastatic ASS1-deficient solid tumours. Further evaluation of this treatment combination is warranted.Subject terms: Cancer, Cancer therapy     

Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non–small-cell Lung Cancer: Analysis by Operability,Fractionation Regimen,Tumor Size,and Tumor Location

Background

Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non–small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients.

Therapeutic cooperation between auranofin,a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8^+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients.