Impact of the Gut Microbiome on Immune Checkpoint Inhibitor Efficacy—A Systematic Review

Background: Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice. Methods: We performed a systematic review in medline to determine (1) whether antibiotics affect ici efficacy, (2) whether baseline gm composition and ici efficacy show any correlations, (3) whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, and (4) whether gm manipulation can alleviate the iraes. Included publications had to be written in English or French and had to describe a quantifiable link between gm composition or its modification and the response to icis or the occurrence of iraes, or both. Results: Of 1451 articles published before December 2018, 13 publications met the inclusion criteria. Five full-text articles and two abstracts highlighted a negative effect of antibiotics on ici efficacy. The composition of the gm was associated with ici efficacy in five full-text articles and one abstract, and with iraes in two full-text articles. In 2 cases, fecal microbiota transplantation was reported to reduce immune colitis. Conclusions: If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy. No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of “responder-associated” bacteria to “non-responder-associated” bacteria seem to be correlated with better patient outcomes. Fecal microbiota transplantation is a promising technique for reducing ici-associated colitis

Comparative Cohort Study of Percutaneous Pedicle Screw Implantation without Versus with Navigation in Patients Undergoing Surgery for Degenerative Lumbar Disc Disease.

The major limitation of computer-based three-dimensional fluoroscopy is increased radiation exposure of patients and operating room staff. Combining spine navigation with intraoperative three-dimensional fluoroscopy (io3DF) can likely overcome this shortcoming, while increasing pedicle screw accuracy rate. We compared data from a cohort of patients undergoing lumbar percutaneous pedicle screw placement using io3DF alone or in combination with spine navigation. This study consisted of 168 patients who underwent percutaneous pedicle screw implantation between 2009 and 2016. The primary endpoint was to compare pedicle screw accuracy between the 2 groups. Secondary endpoints were to compare radiation exposure of patients and operating room staff, duration of surgery, and postoperative complications. In group 1, 438 screws were placed without navigation guidance; in group 2, 276 screws were placed with spine navigation. Mean patient age in both groups was 58.6 ± 14.1 years. The final pedicle accuracy rate was 97.9% in group 1 and 99.6% in group 2. Average radiation dose per patient was significantly larger in group 1 (571.9 mGym) than in group 2 (365.6 mGym) (P = 0.000088). Surgery duration and complication rate were not significantly different between the 2 groups (P > 0.05). io3DF with spine navigation minimized radiation exposure of patients and operating room staff and provided an excellent percutaneous pedicle screw accuracy rate with no permanent complications compared with io3DF alone. This setup is recommended, especially for patients with a complex degenerative spine condition

(In)Efficient Commuting And Migration Choices: Theory And Policy In An Urban Search Model

We develop a monocentric urban search-and-matching model in which workers can choose to commute or to migrate within the region. The equilibrium endogenously allocates the population into three categories: migrants (relocate from their hometown to the city), commuters (traveling to work in the city) and home stayers (remaining in their hometown). We prove that the market equilibrium is usually not optimal: a composition externality may generate under- or over-migration with respect to the central planner’s solution, which in all cases results in under-investment in job vacancies and therefore production. We calibrate the model to the Greater Paris area to reproduce several gradients observed in the data, suggesting over-migration. We show how policy interventions can help to reduce inefficiencies

Global management of brain metastasis from renal cell carcinoma.

During the last decade, major improvements have been made in the treatment of renal cell carcinoma (RCC) with the development and use of multiple tyrosine kinase inhibitors and immune checkpoint inhibitors. Brain metastases in RCC patients (BM-RCC) is associated with poor outcome and their management represents a challenge for clinicians. In most of case, brain metastases in this context require local intervention such as radiotherapy, stereotactic radiotherapy/stereotactic radiosurgery and whole brain radiation therapy. Despite efficacy in extracranial metastases, systemic therapies have modest antitumoral effect on cerebral lesions. In this review, we highlight the benefits and pitfalls of the available therapies in BM-RCC

Implications of the Organ-Specific Immune Environment for Immune Priming Effect of Radiotherapy in Metastatic Setting

With the development of immune checkpoint inhibitors (ICIs), the tumour immune microenvironment (TIME) has been increasingly considered to improve cancer management. The TIME of metastatic lesions is strongly influenced by the underlying immune contexture of the organ in which they are located. The metastatic location itself appears to be an important prognostic factor in predicting outcomes after ICI treatment in cancer patients. Patients with liver metastases are less likely to respond to ICIs than patients with metastases in other organs, likely due to variations in the metastatic TIME. Combining additional treatment modalities is an option to overcome this resistance. Radiotherapy (RT) and ICIs have been investigated together as an option to treat various metastatic cancers. RT can induce a local and systemic immune reaction, which can promote the patient’s response to ICIs. Here, we review the differential impact of the TIME according to metastatic location. We also explore how RT-induced TIME modifications could be modulated to improve outcomes of RT-ICI combinations

An Unusual Case of Ureteral Perforation in Minimally Invasive Pedicle Screw Instrumentation: Case Report and Review of the Literature.

BACKGROUND: Injury of the ureter is a potentially devastating complication most often reported in gynecologic, colorectal, or vascular pelvic surgery or endoscopic procedures for ureteric diseases. We report a rare case of ureteral rupture occurring as a complication of percutaneous pedicle screw placement. CASE DESCRIPTION: A 60-year-old man reported unbearable abdominal pain on the day after right L4-L5 transforaminal intervertebral fusion and percutaneous pedicle screw placement. A computer tomography workup showed contrast media extravasation outside the excretory system consistent with a left ureteral traumatic perforation. The patient underwent left nephrostomy and a double-J stent insertion and subsequently fully recovered. The ureter completely healed, enabling stent removal 5 months later. METHODS: PubMed and EMBASE were screened for ureteral injury caused by posterior lumbar surgery. RESULTS: We found 27 other reports with only 1 other case after minimally invasive transforaminal lumbar interbody. CONCLUSIONS: Complications of minimally invasive pedicle screw placement are often described as dural tear of neurologic impairment. This report shows that unexpected side effects are still possible and spine surgeons should be aware especially when performing minimally invasive procedures, in which, by definition, pedicles are concealed from direct visualization

Radiation therapy-induced left vocal cord paralysis following lung stereotactic body radiation therapy: A case report and review of the literature.

We report the case of a 50-year old women with an oncological history of metastatic breast carcinoma who underwent lung stereotactic body radiation therapy (SBRT) of 60Gy in 8 fractions for a left upper lobe metastatic lesion. Seven months later, she complains about hoarseness and weakness of voice. Tumoral relapse and other frequent etiologies were excluded. The diagnosis of radiation induced left recurrent laryngeal nerve paralysis causing left vocal cord paralysis (VCP) was made. The symptomatology did not improve till the disease progression and death of the patient 29 months after SBRT. VCP after lung SBRT is a rare adverse event that has not yet been well described in the medical literature

Cationic antimicrobial peptides and periodontal physiopathology: A systematic review

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Regression of a melanoma brain metastasis that had appeared after immune checkpoint inhibitor discontinuation: a hypothesis-generating case

We present the case of a 50-year-old woman previously treated with nivolumab-ipilimumab combination therapy for a metastatic melanoma. Despite premature discontinuation of these immune checkpoint inhibitors (ICIs) after 2 cycles due to severe immune-related hepatitis, the patient achieved a complete response. Nine months later, brain magnetic resonance imaging (MRI) showed progression of a single cerebral lesion, and the patient was referred for stereotactic radiosurgery. Unexpectedly, the brain MRI acquired one month later as part of radiosurgery planning showed a spontaneous regression of this lesion, allowing for radiosurgery cancellation. Follow-up imaging showed a sustained response, although the patient did not receive any other oncological treatment. We discuss here the potential immune mechanisms involved in this unusual course and the importance of better understanding the behaviour of tumours in the era of ICIs

Cone-beam computed tomography-guided online-adaptive radiotherapy for inoperable right colon cancer: First in human

We report the case of a medically inoperable patient with localised colon cancer. Due to symptomatic bleeding, definitive radiotherapy (5 daily fractions of 5 Gy) has been performed using cone-beam computed tomography-based online-adaptive radiotherapy (ART). Online-ART enables compensation of interfraction motion of abdominal organs by performing daily delineation of organs at risk (OARs) and target volumes. Daily treatment replanning maximised target volume coverage while lowering the dose to OARs. Intrafraction variation of the tumour was still significant and had to be incorporated in the planning target volume margin computation. After the treatment, the patient did not develop any acute radiotherapy-induced adverse events and had no further rectal bleeding either at the end of the radiotherapy or at oncological follow-up 4 months later. Online-ART for colon cancer is feasible and is a valuable alternative when surgery is not an option