Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.

Evaluation of External Trigeminal Nerve Stimulation to Prevent Cerebral Vasospasm after Subarachnoid Hemorrhage Due to Aneurysmal Rupture: A Randomized, Double-Blind Proof-of-Concept Pilot Trial (TRIVASOSTIM Study).

Cerebral vasospasm remains the most frequent and devastating complication after subarachnoid aneurysmal hemorrhage because of secondary cerebral ischemia and its sequelae. The underlying pathophysiology involves vasodilator peptide release (such as CGRP) and nitric oxide depletion at the level of the precapillary sphincters of the cerebral (internal carotid artery network) and dural (external carotid artery network) arteries, which are both innervated by craniofacial autonomic afferents and tightly connected to the trigeminal nerve and trigemino-cervical nucleus complex. We hypothesized that trigeminal nerve modulation could influence the cerebral flow of this vascular network through a sympatholytic effect and decrease the occurrence of vasospasm and its consequences. We conducted a prospective double-blind, randomized controlled pilot trial to compare the effect of 10 days of transcutaneous electrical trigeminal nerve stimulation vs. sham stimulation on cerebral infarction occurrence at 3 months. Sixty patients treated for aneurysmal SAH (World Federation of Neurosurgical Societies scale between 1 and 4) were included. We compared the radiological incidence of delayed cerebral ischemia (DCI) on magnetic resonance imaging (MRI) at 3 months in moderate and severe vasospasm patients receiving trigeminal nerve stimulation (TNS group) vs. sham stimulation (sham group). Our primary endpoint (the infarction rate at the 3-month follow-up) did not significantly differ between the two groups (p = 0.99). Vasospasm-related infarctions were present in seven patients (23%) in the TNS group and eight patients (27%) in the sham group. Ultimately, we were not able to show that TNS can decrease the rate of cerebral infarction secondary to vasospasm occurrence. As a result, it would be premature to promote trigeminal system neurostimulation in this context. This concept should be the subject of further research.

Lung Ultrasound to Assist ICU Admission Decision-Making Process of COVID-19 Patients With Acute Respiratory Failure.

There is only low-certainty evidence on the use of predictive models to assist COVID-19 patient's ICU admission decision-making process. Accumulative evidence suggests that lung ultrasound (LUS) assessment of COVID-19 patients allows accurate bedside evaluation of lung integrity, with the added advantage of repeatability, absence of radiation exposure, reduced risk of virus dissemination, and low cost. Our goal is to assess the performance of a quantified indicator resulting from LUS data compared with standard clinical practice model to predict critical respiratory illness in the 24 hours following hospital admission. DESIGN: Prospective cohort study. SETTING: Critical Care Unit from University Hospital Purpan (Toulouse, France) between July 2020 and March 2021. PATIENTS: Adult patients for COVID-19 who were in acute respiratory failure (ARF), defined as blood oxygen saturation as measured by pulse oximetry less than 90% while breathing room air or respiratory rate greater than or equal to 30 breaths/min at hospital admission. Linear multivariate models were used to identify factors associated with critical respiratory illness, defined as death or mild/severe acute respiratory distress syndrome (Pao2/Fio2 < 200) in the 24 hours after patient's hospital admission. INTERVENTION: LUS assessment. MEASUREMENTS AND MAIN RESULTS: One hundred and forty COVID-19 patients with ARF were studied. This cohort was split into two independent groups: learning sample (first 70 patients) and validation sample (last 70 patients). Interstitial lung water, thickening of the pleural line, and alveolar consolidation detection were strongly associated with patient's outcome. The LUS model predicted more accurately patient's outcomes than the standard clinical practice model (DeLong test: Testing: z score = 2.50, p value = 0.01; Validation: z score = 2.11, p value = 0.03). CONCLUSIONS: LUS assessment of COVID-19 patients with ARF at hospital admission allows a more accurate prediction of the risk of critical respiratory illness than standard clinical practice. These results hold the promise of improving ICU resource allocation process, particularly in the case of massive influx of patients or limited resources, both now and in future anticipated pandemics.

Influence of Deep Serratus Anterior Plane Block on Chronic Pain at 3 Months After Breast-Conserving Surgery: Prospective, Cohort Study.

OBJECTIVES: In 2015, we evaluated our practices regarding pain after breast-conserving surgery. Thereafter, we have adapted our practices by performing a systematic deep serratus plane block before the surgical incision. In 2019, we assessed the impact of these changes in terms of chronic pain. The main objective of this study was to evaluate the prevalence of chronic pain 3 months after this type of surgery. MATERIALS AND METHODS: All patients treated with breast-conserving surgery as outpatients were included in this prospective study between April and July 2019. After inducing general anesthesia, 20 mL of ropivacaine 3.75 mg/mL were injected under the serratus muscle. Morphine titration was performed in the recovery room according to pain scores. A pain and quality of life questionnaire was sent 3 months after surgery. A backward logistic regression model was applied to calculate the adjusted odds ratios. RESULTS: The final analysis involved 137 patients. Three months after surgery, 43 patients (31%) reported persistent pain related to the surgery. Maximum pain in the last 24 hours was moderate to severe in 60% of cases, 16 patients (35%) took painkillers. Morphine titration in the recovery room was required in 25 patients (18%). Younger age and the use of lidocaine to prevent after injection of propofol during general anesthesia induction appeared to be protective factors for the risk of pain at 3 months (secondary endpoints). DISCUSSION: No persistent pain at 3 months was reported in 69% of cases. Furthermore, the use of a deep serratus anterior plane block before the surgical incision has limited the need for morphine titration in the recovery room to <1 patient in 5. These evaluations of professional practices should be encouraged.

Evaluation of the impact of the COVID-19 lockdown on the quality of life of patients monitored for cancer who practice an adapted physical activity: rugby for health.

PURPOSE: The benefits of regular physical exercise on the tolerability of cancer treatments, quality of life and survival rates post-diagnosis have been demonstrated but all supervised physical activities have been interrupted due to the global health crisis and the need for lockdown to halt the spread of SARS-CoV-2. To reintroduce activities post-lockdown, we wanted to assess the impact of the COVID-19 lockdown on the quality of life and the psychological status of patients who practice an adapted physical activity such as rugby for health. METHODS: The evaluation was conducted in two phases: an initial self-questionnaire comprised of 42 questions sent to all participants to assess the impact of lockdown and a second assessment phase in the presence of the participants. We assessed anthropometric data, functional fitness parameters, quality of life and the psychosocial status of the subjects. The data were compared to pre-lockdown data as part of a standardised follow-up procedure for patients enrolled in the programme. RESULTS: 105/120 (87.5%) individuals responded to the rapid post-lockdown survey analysis. In 20% of the cases, the patients reported anxiety, pain, a decline in fitness and a significant impact on the tolerability of cancer treatments. Twenty-seven patients agreed to participate in the individual analysis. Following lockdown, there was a significant decrease in the intensity of physical activity (p = 8.223e-05). No post-lockdown changes were noted in the assessments that focus on the quality of life and the level of psychological distress. Conversely, there was a significant correlation between the total of high energy expended during lockdown and the quality of life (p = 0.03; rho = 0.2248) and the level of psychological distress post-lockdown (p = 0.05; rho = - 0.3772). CONCLUSION: Lockdown and reduced physical activity, particularly leisure activities, did not impact the overall health of the patients. However, there was a significant correlation with the level of physical activity since the higher the level of physical activity, the better the quality of life and the lower the level of psychological distress.

Accuracy of pulse pressure variations for fluid responsiveness prediction in mechanically ventilated patients with biphasic positive airway pressure mode.

The accuracy of pulse pressure variation (PPV) to predict fluid responsiveness using pressure-controlled (PC) instead of volume-controlled modes is under debate. To specifically address this issue, we designed a study to evaluate the accuracy of PPV to predict fluid responsiveness in severe septic patients who were mechanically ventilated with biphasic positive airway pressure (BIPAP) PC-ventilation mode. 45 patients with sepsis or septic shock and who were mechanically ventilated with BIPAP mode and a target tidal volume of 7-8 ml/kg were included. PPV was automatically assessed at baseline and after a standard fluid challenge (Ringer's lactate 500 ml). A 15% increase in stroke volume (SV) defined fluid responsiveness. The predictive value of PPV was evaluated through a receiver operating characteristic (ROC) curve analysis and "gray zone" statistical approach. 20 (44%) patients were considered fluid responders. We identified a significant relationship between PPV decrease after volume expansion and SV increase (spearman ρ = - 0.5, p < 0.001). The area under ROC curve for PPV was 0.71 (95%CI 0.56-0.87, p = 0.007). The best cut-off (based on Youden's index) was 8%, with a sensitivity of 80% and specificity of 60%. Using a gray zone approach, we identified that PPV values comprised between 5 and 15% do not allow a reliable fluid responsiveness prediction. In critically ill septic patients ventilated under BIPAP mode, PPV appears to be an accurate method for fluid responsiveness prediction. However, PPV values comprised between 5 and 15% constitute a gray zone that does not allow a reliable fluid responsiveness prediction.

Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy.

INTRODUCTION: Salvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence. MATERIAL AND METHODS: From January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 - Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy. RESULTS: After a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of > or = to 3 was found. CONCLUSIONS: Our series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials.

Obturator nerve block does not provide analgesic benefits in total hip arthroplasty under multimodal analgesic regimen: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Although regional analgesia is considered an important component of optimal pain management, use of peripheral nerve blocks for total hip arthroplasty remains controversial. Since the obturator nerve innervates the anteromedial part of the joint capsule, we hypothesized that an obturator nerve block would decrease the opioid consumption after total hip arthroplasty. METHODS: In this single center, prospective, triple blinded study, we randomly allocated 60 patients undergoing total hip arthroplasty under opioid-sparing total intravenous general anesthesia to a preoperative obturator nerve block or a sham block (placebo group) using 20 mL of ropivacaine 0.2% or saline, respectively. All patients received a multimodal analgesic regimen with non-opioid analgesics including periarticular local infiltration analgesia. The primary outcome was the intravenous opioid consumption in the post-anesthesia care unit. RESULTS: Median (IQR) intravenous oxycodone consumption in the post-anesthesia care unit was 4 (2, 7.5) mg in the obturator nerve block group and 3 (0, 4) mg in the placebo group (p=0.05). There were no differences in pain scores between groups in the first 24 hours except at arrival on the surgical ward with significant higher pain scores in the placebo group (p=0.03). The ability to stand up and walk within 24 hours was comparable between groups as was the time to first walk (180 (90, 720) vs 240 (120, 780) min for the obturator nerve block and placebo groups, respectively; p=0.62). CONCLUSIONS: Obturator nerve block did not improve postoperative opioid consumption after total hip arthroplasty performed under general anesthesia with a multimodal analgesic regimen. TRIAL REGISTRATION NUMBER: NCT04085640.

Correlation between toxicity and dosimetric parameters for adjuvant intensity modulated radiation therapy of breast cancer: a prospective study.

ORCID: 0000-0001-6019-7309. In the treatment of breast cancer, intensity-modulated radiation therapy (IMRT) reportedly reduces the high-dose irradiation of at-risk organs and decreases the frequency of adverse events (AEs). Comparisons with conventional radiotherapy have shown that IMRT is associated with lower frequencies of acute and late-onset AEs. Here, we extended a prospective, observational, single-center study of the safety of IMRT to a second investigating center. Patients scheduled for adjuvant IMRT after partial or total mastectomy were given a dose of 50 Gy (25 fractions of 2 Gy over 5 weeks), with a simultaneous integrated boost in patients having undergone conservative surgery. 300 patients were included in the study, and 288 were analyzed. The median follow-up period was 2.1 years. The 2-year disease-free survival rate [95% CI] was 93.4% [89.2-96.0%]. Most AEs were mild. The most common AEs were skin-related-mainly radiodermatitis [in 266 patients (92.4%)] and hyperpigmentation (in 178 (61.8%)). 35% and 6% of the patients presented with grade 2 acute skin and esophageal toxicity, respectively. Only 4 patients presented with a grade 3 event (radiodermatitis). Smoking (odds ratio) [95% CI] = 2.10 [1.14-3.87]; p = 0.017), no prior chemotherapy (0.52 [0.27-0.98]; p = 0.044), and D98% for subclavicular skin (1.030 [1.001-1.061]; p = 0.045) were associated with grade ≥ 2 acute AEs. In a univariate analysis, the mean dose, (p < 0.0001), D2% (p < 0.0001), D50% (p = 0.037), D95% (p = 0.0005), D98% (p = 0.0007), V30Gy (p < 0.0001), and V45Gy (p = 0.0001) were significantly associated with grade ≥ 1 acute esophageal AEs. In a multivariate analysis, D95% for the skin (p < 0.001), D98% for the subclavicular skin and low D95% for the internal mammary lymph nodes were associated with grade ≥ 1 medium-term AEs. The safety profile of adjuvant IMRT after partial or total mastectomy is influenced by dosimetric parameters. TRIAL REGISTRATION: ClinicalTrials.gov NCT02281149.

Machine learning methods to improve bedside fluid responsiveness prediction in severe sepsis or septic shock: an observational study.

BACKGROUND: Passive leg raising (PLR) predicts fluid responsiveness in critical illness, although restrictions in mobilising patients often preclude this haemodynamic challenge being used. We investigated whether machine learning applied on transthoracic echocardiography (TTE) data might be used as a tool for predicting fluid responsiveness in critically ill patients. METHODS: We studied, 100 critically ill patients (mean age: 62 yr [standard deviation: 14]) with severe sepsis or septic shock prospectively over 24 months. Transthoracic echocardiography measurements were performed at baseline, after PLR, and before and after a standardised fluid challenge in learning and test populations (n=50 patients each). A 15% increase in stroke volume defined fluid responsiveness. The machine learning methods used were classification and regression tree (CART), partial least-squares regression (PLS), neural network (NNET), and linear discriminant analysis (LDA). Each method was applied offline to determine whether fluid responsiveness may be predicted from left and right cardiac ventricular physiological changes detected by cardiac ultrasound. Predictive values for fluid responsiveness were compared by receiver operating characteristics (area under the curve [AUC]; mean [95% confidence intervals]). RESULTS: In the learning sample, the AUC values were PLR 0.76 (0.62-0.89), CART 0.83 (0.73-0.94), PLS 0.97 (0.93-1), NNET 0.93 (0.85-1), and LDA 0.90 (0.81-0.98). In the test sample, the AUC values were PLR 0.77 (0.64-0.91), CART 0.68 (0.54-0.81), PLS 0.83 (0.71-0.96), NNET 0.83 (0.71-0.94), and LDA 0.85 (0.74-0.96) respectively. The PLS model identified inferior vena cava collapsibility, velocity-time integral, S-wave, E/Ea ratio, and E-wave as key echocardiographic parameters. CONCLUSIONS: Machine learning generated several models for predicting fluid responsiveness that were comparable with the haemodynamic response to PLR.

Total knee arthroplasty under quadruple nerve block with ropivacaine 0.32%: effect of addition of intravenous dexmedetomidine to intravenous dexamethasone on analgesic duration.

BACKGROUND AND OBJECTIVES: Peripheral nerve blocks reduce postoperative pain and enhance recovery after total knee arthroplasty (TKA). This study aims to assess the benefits of addition of intravenous dexmedetomidine (DexM) to intravenous dexamethasone on the analgesic duration of quadruple nerve blocks. METHODS: This double-blind, randomized, controlled trial prospectively enrolled 90 patients scheduled for TKA under quadruple nerve blocks (sciatic, femoral, obturator, and lateral femoral cutaneous nerves blocks) with 70 mL, 0.32% ropivacaine. All patients received systemic dexamethasone 10 mg. Patients were randomized to receive DexM (2 µg/kg, intravenous) or placebo (1:1 ratio). The primary endpoint was the duration of analgesia defined as the time to first request for rescue analgesia (oxycodone). RESULTS: Kaplan-Meier curves for the first analgesic request were similar between groups (log-rank test; p=0.27). Median (IQR) duration of analgesia was similar between placebo (1575 min (1211-1952)) and DexM (1470 min (1263-1700)) groups (p=0.56). Cumulative consumption of oxycodone at the 48th hour was 20 mg (10-30) and 30 mg (20-40) in placebo and DexM groups, respectively (p=0.14). The day after surgery, 93% and 89% of patients were able to walk in placebo and DexM groups, respectively (p=0.46). Intravenous DexM was associated with bradycardia, hypotension and longer recovery room stay (p<0.05 for all comparisons). CONCLUSIONS: In a multimodal analgesic regimen, addition of systemic DexM (2 µg/kg) to systemic dexamethasone does not prolong the analgesic duration of quadruple nerve block with ropivacaine 0.32% after TKA. TRIAL REGISTRATION NUMBER: NCT03834129.

How Should we Use Multicolumn Spinal Cord Stimulation to Optimize Back Pain Spatial Neural Targeting? A Prospective, Multicenter, Randomized, Double-Blind, Controlled Trial (ESTIMET Study).

BACKGROUND: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP). OBJECTIVE: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead. MATERIALS AND METHODS: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up. RESULTS: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p < 0.0001). CONCLUSION: The ESTIMET study confirms the significant benefit experienced on chronic BP by patients implanted with multicolumn SCS, independently from multicolumn lead programming. These good clinical outcomes might result from the specific architecture of the multicolumn lead, giving the opportunity to select initially the best column on a multicolumn grid and to optimize neural targeting with low-energy requirements. However, involving more columns than one does not appear necessary, once initial spatial targeting of the "sweet spot" has been achieved. Our findings suggest that this spatial concept could also be transposed to cylindrical leads, which have drastically improved their capability to shape the electrical field, and might be combined with temporal resolution using SCS new modalities.

Japanese Acupuncture: A Complementary Approach to the Meridian Balance Method.

The association of acupuncture points requires realization of synergistic combinations to be as effective as possible while avoiding possible aggravations. To this end, the meridian balance method is an effective tool. It is based on the 6 systems of Richard T.-F. Tan, MD, which derive from 6 principles of traditional knowledge: (1) Chinese meridian-name sharing; (2) branching meridians (Bie-Jing); (3) interior-exterior pairs (Biao-Li); (4) Chinese clock opposite; (5) Chinese clock neighbor; and (6) the same meridian. However, the results seem to unstable over time, and, therefore, synergies with "root" treatment based on Japanese meridian therapy could help stabilize the therapeutic effects of the meridian balance method. Japanese meridian therapy uses pulse diagnosis to identify 4 basic primary patterns: (1) Liver Deficiency, generally treated with a combination of acupuncture points LR8-KI10; (2) Kidney Deficiency, treated with LU 5-KI 7; (3) Spleen Deficiency, treated with PC 7-SP 3; and (4) Lung Deficiency, treated with SP 3-LU 9. After reviewing the main principles of Japanese acupuncture, a nondogmatic approach coupling Japanese meridian therapy with Dr. Tan's balance method is proposed in order to use the best of each of the 2 methods in an integrative approach.

New Insights into Expression of Hormonal Receptors by Meningiomas.

OBJECTIVE: Meningiomas have a female predilection, which is even stronger for spinal than for intracranial meningiomas. The relationship between meningiomas and endogenous or exogenous sex hormones such as cyproterone acetate (CPA) is well documented, yet their underlying mechanism remains unknown. Clarification of the expression profile of hormonal receptors by meningiomas would help us to better understand their hormonal susceptibility. METHODS: We used tissue microarray and immunohistochemistry to determine the receptor status of the 3 main sex hormones: androgen (AR), estrogen, and progesterone (PR) in 30 intracranial meningiomas, 30 spinal meningiomas, and 30 meningiomas developed on CPA. RESULTS: AR status was positive in 73% of meningiomas in the intracranial group, 87% of meningiomas in the CPA group, and in all meningiomas in the spinal group. Estrogen status was positive in only 7% of meningiomas in the intracranial group and in only 3% of meningiomas in the CPA group but in 30% of meningiomas in the spinal group. PR status was positive in 90% of meningiomas in the intracranial group, in 97% of meningiomas in the CPA group, and in 87% of meningiomas in the spinal group. These specific hormonal receptor statuses based on immunoreactive score were reflected on staining intensities. Furthermore, AR and PR expression was correlated in each group. CONCLUSIONS: Our study shows that intracranial meningiomas, spinal meningiomas, and meningiomas developed on CPA express specific hormonal receptor patterns. This result invites the scientific community to review the potential role of AR in the unbalanced sex ratio of meningiomas.

Prospective Study of Intensity-Modulated Radiation Therapy for Locally Advanced Breast Cancer.

The objective of this study was to evaluate the acute and medium-term toxicities, the quality of life, and aesthetic results of patients with breast cancer (BC) treated with tomotherapy. This was a prospective study, including patients with BC treated by tomotherapy. Radiation therapy delivered 50 Gy in 25 fractions to the breast or chest wall and to lymph node areas, with a simultaneous integrated boost at a dose of 60 Gy at the tumor bed in cases of breast conservative surgery. We included 288 patients, 168 and 120 treated with breast-conserving surgery and mastectomy respectively. Two hundred sixty patients (90.3%) received lymph node irradiation. Median follow-up was 25 months (6-48). Acute dermatitis was observed in 278 patients (96.5%), mostly grade 1 (59.7%). The aesthetic aspect of the breast at one year was reported as "good" or "excellent" in 84.6% of patients. The patients' quality of life improved over time, especially those treated with chemotherapy. The two-year overall survival and disease-free survival were 97.8% (95% confidence interval (CI): 94.1-99.2%), and 93.4% (95% CI: 89.2-96.0%) respectively. Tomotherapy for locally advanced BC has acceptable toxicity, supporting its use in this indication; however, longer follow-up is needed to assess long-term outcomes.

Outcomes of pre-operative brachytherapy followed by hysterectomy for early cervical cancer.

OBJECTIVE: The standard of care for early cervical cancer is radical hysterectomy; however, consideration of pre-operative brachytherapy has been explored. We report our experience using pre-operative brachytherapy plus Wertheim-type hysterectomy to treat early stage cervical cancer. METHODS: This single-center study evaluated consecutive patients with histologically proven node-negative early stage cervical cancer (International Federation of Gynecology and Obstetrics 2009 stage IB1-IIB) that was treated using pre-operative brachytherapy and hysterectomy. Pre-brachytherapy staging was performed using magnetic resonance imaging (MRI) and pelvic lymph node assessment was performed using lymphadenectomy. The tumor and cervical tissues were treated using brachytherapy (total dose 60 Gy) followed by Wertheim-type hysterectomy. The study included patients from January 2000 to December 2013. RESULTS: A total of 80 patients completed a median follow-up of 6.7 years (range 5.4-8.5). The surgical specimens revealed a pathological complete response for 61 patients (76%). Patients with incomplete responses generally had less than 1 cm residual tumor at the cervix, and only one patient had lymphovascular space involvement. The estimated 5-year rates were 88% for overall survival (95% CI 78% to 94%) and 82% for disease-free survival (95% CI 71% to 89%). Toxicities were generally mild-to-moderate, including 26 cases (33%) of grade 2 late toxicity and 10 cases (13%) of grade 3 late toxicity. Univariate analyses revealed that poor disease-free survival was associated with overweight status (≥25 kg/m2, HR 3.05, 95% CI 1.20 to 7.76, p=0.019) and MRI tumor size >3 cm (HR 3.05, 95% CI 1.23 to 7.51, p=0.016). CONCLUSIONS: Pre-operative brachytherapy followed by Wertheim-type hysterectomy may be safe and effective for early stage cervical cancer, although poorer outcomes were associated with overweight status and MRI tumor size >3 cm.

Histomolecular characterization of intracranial meningiomas developed in patients exposed to high-dose cyproterone acetate: an antiandrogen treatment.

BACKGROUND: Meningiomas are the most common primary intracranial tumors in adults. The relationship between meningiomas and exogenous sex hormones such as cyproterone acetate (CPA) is well documented, yet the underlying mechanisms remain unknown. Defining the histomolecular status of meningiomas developed on CPA would help us to better understand the oncogenesis of these tumors. METHODS: We identified 30 patients operated for a meningioma after long-term high-dose CPA therapy and with a history of CPA discontinuation before establishing the indication for surgical intervention. We used array-comparative genomic hybridization (to characterize copy number changes in those 30 meningiomas and subsequently performed next-generation sequencing with the National Institute of Cancer (INCa) solid tumor panel, which is a targeted panel of clinically actionable genes. We also examined grade, type, and clinical features. RESULTS: We identified AKT1 mutations or PIK3CA mutations in 33.3% of CPA meningiomas. AKT1 and PIK3CA mutations were mutually exclusive. Enrichment in oncogenic PIK3CA mutations in the CPA cohort was detected. CPA meningiomas showed chromosomal stability and were located mainly in the skull base. Ninety percent of CPA meningiomas were low-grade meningiomas and 63.4% were meningotheliomas. Half of our CPA cohort had microcystic components. CONCLUSION: Our study shows that low-grade meningothelial meningiomas of the skull base are predominant in CPA meningiomas. We identified PIK3CA/AKT1 pathway as a hypothetical actor in onco-pharmacological interaction between meningiomas and CPA. This signaling pathway could be an interesting target for precision medicine trials in meningioma patients who have been subjected to CPA. Our results could invite the scientific community to review the current classification of meningiomas and to evolve toward more specific histomolecular classification.

Perineural Versus Systemic Dexamethasone in Front-Foot Surgery Under Ankle Block: A Randomized Double-Blind Study.

BACKGROUND AND OBJECTIVES: Among the different adjuvants, dexamethasone is one of the most accepted to prolong the effect of local anesthetics. This study aims to determine the superiority of perineural over systemic dexamethasone administration after a single-shot ankle block in metatarsal osteotomy. METHODS: We performed a prospective, double-blind, randomized study. A total of 100 patients presenting for metatarsal osteotomy with an ankle block were randomized into 2 groups: 30 mL ropivacaine 0.375% + perineural dexamethasone 4 mg (1 mL) + 2.5 mL of systemic saline solution (PNDex group, n = 50) and 30 mL ropivacaine 0.375% + 1 mL of perineural saline solution + intravenous dexamethasone 10 mg (2.5 mL) (IVDex group, n = 50). The primary end point was the duration of analgesia defined as the time between the performance of the ankle block and the first administration of rescue analgesia with tramadol. RESULTS: Time period to first rescue analgesia with tramadol was similar in the IVDex group and the PNDex group. Data are expressed as mean (SD) or median (range). Duration of analgesia was 23.2 (9.5) hours in the IVDex group and 19 (8.2) hours in the PNDex group (P = 0.4). Consumption of tramadol during the first 48 hours was 0 mg (0-150 mg) in the IVDex group versus 0 mg (0-250 mg) in the PNDex group (P = 0.59). Four (8%) and 12 (24%) patients reported nausea or vomiting in the IVDex group and the PNDex group, respectively (P = 0.03). CONCLUSIONS: In front-foot surgery, perineural and systemic administrations of dexamethasone are equivalent for postoperative pain relief when used as an adjuvant to ropivacaine ankle block. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier NCT02904538.