The <Emphasis Type="Italic">i</Emphasis><Superscript>2</Superscript><Emphasis Type="Italic">Snake</Emphasis> Robotic Platform for Endoscopic Surgery

Endoscopic procedures have transformed minimally invasive surgery as they allow the examination and intervention on a patient’s anatomy through natural orifices, without the need for external incisions. However, the complexity of anatomical pathways and the limited dexterity of existing instruments, limit such procedures mainly to diagnosis and biopsies. This paper proposes a new robotic platform: the Intuitive imaging sensing navigated and kinematically enhanced (\(i^{2}Snake\)) robot that aims to improve the field of endoscopic surgery. The proposed robotic platform includes a snake-like robotic endoscope equipped with a camera, a light-source and two robotic instruments, supported with a robotic arm for global positioning and for insertion of the \(i^{2}Snake,\) and a master interface for master–slave teleoperation. The proposed robotic platform design focuses on ergonomics and intuitive control. The control workflow was first validated in simulation and then implemented on the robotic platform. The results are consistent with the simulation and show the clear clinical potential of the system. Limitations such as tendon backlash and elongation over time will be further investigated by means of combined hardware and software solutions. In conclusion, the proposed system contributes to the field of endoscopic surgical robots and could allow to perform more complex endoscopic surgical procedures while reducing patient trauma and recovery time.     

Students’ perspectives on research and assessment of a model template designed to guide beginners in research in a medical school in Cameroon

Background

Research activities for medical students and residents (trainees) are expected to serve as a foundation for the acquisition of basic research skills. Some medical schools therefore recommend research work as partial requirement for certification. However medical trainees have many difficulties concerning research, for which reason potential remedial strategies need to be constantly developed and tested. The views of medical trainees are assessed followed by their use and appraisal of a novel “self-help” tool designed for the purposes of this study with potential for improvement and a wider application.

Methods

This study was a cross-sectional survey of volunteering final-year medical students and residents of a medical school in Cameroon.

Results

This study surveyed the opinions of a total of 120 volunteers of which 82 (68%) were medical students. Three out of 82 (4%) medical students reported they had participated in research activities with a publication versus 10 out of 38 residents (26%). The reported difficulties in research for these trainees included referencing of material (84%), writing a research proposal (79%), searching for literature (73%) and knowledge of applicable statistical tests (72%) amongst others. All participants declared the “self-help” tool was simple to use, guided them to think and better understand their research focus.

Conclusion

Medical trainees require much assistance on research and some “self-help” tools such as the template used in this study might be a useful adjunct to didactic lectures.

     

The iron chelator deferasirox synergises with chemotherapy to treat triple‐negative breast cancers

To ensure their high proliferation rate, tumor cells have an iron metabolic disorder causing them to have increased iron needs, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of new therapeutic approaches is urgently needed for patients with triple‐negative tumors, which frequently relapse after chemotherapy and suffer from a lack of targeted therapies. In this study, we demonstrated that deferasirox (DFX) synergises with standard chemotherapeutic agents such as doxorubicin, cisplatin and carboplatin to inhibit cell proliferation and induce apoptosis and autophagy in triple‐negative breast cancer (TNBC) cells. Moreover, the combination of DFX with doxorubicin and cyclophosphamide delayed recurrences in breast cancer patient‐derived xenografts without increasing the side‐effects of chemotherapies alone or altering the global iron storage of mice. Antitumor synergy of DFX and doxorubicin seems to involve downregulation of the phosphoinositide 3‐kinase and nuclear factor‐κB pathways. Iron deprivation in combination with chemotherapy could thus help to improve the effectiveness of chemotherapy in TNBC patients without increasing toxicity. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Human papillomavirus genotype and viral load agreement between paired first-void urine and clinician-collected cervical samples

The performance and acceptability of first-void urine as specimen for the detection of HPV DNA in a Belgian referral population was evaluated using an optimized sample collection and processing protocol. One hundred ten first-void urine and cervical samples were collected from 25- to 64-year-old women who were referred for colposcopy (January–November 2016). Paired samples were analyzed by the Riatol qPCR HPV genotyping assay. Acceptability data were gathered through questionnaires (NCT02714127). A higher high-risk HPV DNA prevalence was observed in first-void urine (n?=?76/110) compared to cervical samples (n?=?73/110), with HPV31 and HPV16/31 being most prevalent correspondingly. For both any and high-risk HPV DNA, good agreement was observed between paired samples (Cohen’s Kappa of 0.660 (95% CI: 0.486–0.833) and 0.688 (95% CI: 0.542–0.835), respectively). In addition, significant positive correlations in HPV copies (per microliter of DNA extract) between paired samples were observed for HPV16 (r_s?=?0.670; FDR (false discovery rate)-adjusted p?=?0.006), HPV18 (r_s?=?0.893; FDR-adjusted p?=?0.031), HPV31 (r_s?=?0.527; FDR-adjusted p?=?0.031), HPV53 (r_s?=?0.691; FDR-adjusted p?=?0.017), and HPV68 (r_s?=?0.569; FDR-adjusted p?=?0.031). First-void urine sampling using a first-void urine collection device was preferred over a clinician-collected cervical sample. And mostly, first-void urine sampling at home was favored over collection at the clinic or the general practitioner’s office. First-void urine sampling is a highly preferred, non-invasive method that ensures good agreement in HPV DNA (copies) with reference cervical samples. It is particularly interesting as a screening technique to reach non-participants, and its clinical performance should be further evaluated.     

Rapid Push vs Pump-Infused Subcutaneous Immunoglobulin Treatment: a Randomized Crossover Study of Quality of Life in Primary Immunodeficiency Patients

Purpose

Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient’s life quality index (LQI).

Methods

This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%.

Results

Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p?=?0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump.

Conclusions

Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician’s armamentarium which is preferred by some patients and is cost-effective.

ClinicalTrials.gov Identifier

NCT02180763

Clinical Implications

Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week.

Capsule Summary

This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician’s armamentarium.

     

In vivo MRI for effective non‐invasive detection and follow‐up of an orthotopic mouse model of lung cancer

One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this study, we evaluated the potential of optimized lung MRI techniques as a completely non‐invasive approach for non‐small‐cell lung cancer (NSCLC) MRI in vivo detection and follow‐up in a mouse model of lung adenocarcinoma expressing the luciferase gene. Bioluminescent lung tumour cells were orthotopically implanted in immuno‐deficient mice. Ultra‐short echo‐time (UTE) MRI free‐breathing acquisitions were compared with standard gradient‐echo lung MRI (FLASH) using both respiratory‐gated and free‐breathing protocols. The MRI findings were validated against bioluminescence imaging (BLI) and gold‐standard histopathology analysis. Adenocarcinoma‐like pathological tissue was successfully identified in all the mice with gated‐FLASH and non‐gated UTE MRI, and good tumour co‐localization was found between MRI, BLI and histological analyses. An excellent or good correlation was found between the measured bioluminescent signal and the total tumour volumes quantified with UTE MRI or gated‐FLASH MRI, respectively. No significant correlation was found when the tumours were segmented on non‐gated MR FLASH images. MRI was shown to be a powerful imaging tool able to detect, quantify and longitudinally monitor the development of sub‐millimetric NSCLCs. To our knowledge, this is the first study which proves the feasibility of a completely non‐invasive MRI quantitative detection of lung adenocarcinoma in freely breathing mice. The absence of ionizing radiation and the high‐resolution of MRI, along with the complete non‐invasiveness and good reproducibility of the proposed non‐gated protocol, make this imaging tool ideal for direct translational applications. Copyright © 2014 John Wiley & Sons, Ltd.     

The small heat‐shock protein αB‐crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF‐β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB‐crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB‐crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad‐dependent pathway. We demonstrate here that αB‐crystallin is strongly expressed in fibrotic lung tissue from IPF patients and in vivo rodent models of pulmonary fibrosis. We also show that αB‐crystallin‐deficient mice are protected from bleomycin‐induced fibrosis. Similar protection from fibrosis was observed in αB‐crystallin KO mice after transient adenoviral‐mediated over‐expression of IL‐1β or TGF‐β1. We show in vitro in primary epithelial cells and fibroblasts that αB‐crystallin increases the nuclear localization of Smad4, thereby enhancing the TGF‐β1–Smad pathway and the consequent activation of TGF‐β1 downstream genes. αB‐crystallin over‐expression disrupts Smad4 mono‐ubiquitination by interacting with its E3–ubiquitin ligase, TIF1γ, thus limiting its nuclear export. Conversely, in the absence of αB‐crystallin, TIF1γ can freely interact with Smad4. Consequently, Smad4 mono‐ubiquitination and nuclear export are favoured and thus TGF‐β1–Smad4 pro‐fibrotic activity is inhibited. This study demonstrates that αB‐crystallin may be a key target for the development of specific drugs in the treatment of IPF or other fibrotic diseases. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.