Data Monitoring Committees and clinical trials: From scientific justification to organisation.

Clinical trials often last several months or even several years. As the trial progresses, it can be tempting to find out whether the data obtained already answers the question posed at the start of the trial in order to stop inclusions or monitoring earlier. However, knowing and taking into account interim results can sometimes compromise the integrity of the results, which is counterproductive. To minimise this risk and ensure that the treatments are assessed reliably, safety and/or efficacy criteria are monitored during the study by a Data Monitoring Committee. After receiving the results confidentially, the Data Monitoring Committee assesses the benefit/risk ratio of the study treatment and recommends that the trial be continued, modified or terminated. Data Monitoring Committee members issuing these recommendations have an important responsibility: a hasty decision to end the trial may lead to inconclusive results unable to answer the initial question and, inversely, delaying the decision to end the trial may expose the subjects to potentially ineffective or even harmful interventions. The Data Monitoring Committee's task is therefore particularly complex. With this in mind, the round table discussion at the Giens workshops was a chance to review the scientific justification for creating Data Monitoring Committees and to recall the need for their members to receive comprehensive training on the complexities of multiple analyses, confidentiality requirements applying to the results and the need for them to be aware that recommendations to end a trial must be based on data that is robust enough to assess the benefit/risk ratio of the treatment studied.

Single Dose Steroid Injection After Loss of Signal (LOS) During Thyroid Surgery is Effective to Recover Electric Signal Avoiding Vocal Cord Palsy and the Need of Staged Thyroidectomy: Prospective Evaluation on 702 Patients.

BACKGROUND: Steroids are often used for the management of vocal cord palsy after thyroid surgery. There are no reports in the current literature of their intraoperative use, immediately after a loss of signal during neuromonitoring (LOS). We evaluate the impact of a single dose of 4 mg of dexamethasone on laryngeal nerve function, administrated at the time of a LOS during a nerve-monitored thyroidectomy. METHODS: A prospective not randomized study was performed, dividing patients in two groups, when a LOS was detected. LOS was defined as an electromyographic signal (EMG) inferior to 100 µV when stimulating the inferior laryngeal nerve, according to international guidelines. In group 1 (G1), surgeon waits for signal's recovery up to 20 min. Absence of a detectable signal after 20 min was predictive of vocal cord palsy; if it affected the first side of surgery the procedure was interrupted to avoid the risk of bilateral nerve palsy. In group 2 (G2), 4 mg of dexamethasone were injected within 10 min from a detected LOS, waiting 10 min for its effects. An EMG value > to 200 µV within 20' after steroid administration was predictive of full recovery and normal post-operatory vocal cord function. Vocal cords motility was checked at postoperative day 1 in all patients by an experienced ENT. RESULTS: Between January 2017 and December 2018, 702 patients underwent thyroid surgery under intermittent intraoperative nerve monitoring by two expert surgeons. A LOS was found in 22 patients in G1 and 16 in G2. Four patients in G1 spontaneously recovered electric signal (18.2%), while in G2 a signal was recovered in 14/16 patients (87.5%) (p < 0.001). This immediate effect was monitored by EMG, showing the increase in potentials at 10, 15 and 20 min after injection. ENT evaluation found vocal cord palsy, respectively, in 18/22 and 1/16 patients (G1 vs G2, p < 0.001). One of the patients in G2 who recovered electric signal presented transient palsy, fully recovered at 2 months, while the two patients who had a signal < 200 µV did not present postoperative cord palsy. In G1, 10/18 palsy were definitive. No permanent palsies were presents in G2. CONCLUSION: A single 4 mg iv dexamethasone injection within 10 min form a LOS during thyroid surgery exerts a therapeutic action, measurable by EMG modifications. It avoids vocal nerve palsy and the need of a staged thyroidectomy. It may also protect from permanent cord palsy, but the mechanism is unknown.

Does the risk of compressive hematoma after thyroidectomy authorize 1-day surgery?

BACKGROUND: Compressive hematoma after thyroidectomy is a rare complication (1%) but can potentially be severe. The aim of this study was to search for risk factors, in particular the use of anticoagulants or antiplatelet medication, and to see if the delay of hematoma formation would require 1-day surgery performed in a careful manner. MATERIALS AND METHODS: Retrospective review of 6,830 patients undergoing thyroidectomy in a single institution (1991 to 2006) identified 70 patients with hematomas requiring reoperation. Case controls (210 patients) were matched for age, gender, year of operation, type of thyroid disease, and type of operation. The notion of anticoagulant or antiplatelet medication was particularly studied. The delay of hematoma formation and the cause of bleeding were studied in univariate analysis by a chi-squared test and a Fischer's test. RESULTS: In univariate analysis, the formation of hematoma is not related to age, gender, type of thyroid disease, or type of bleeding. The pre or intraoperatory administration of anticoagulant or antiplatelet medication did not influence hematoma formation. Thirty-seven hematomas (53%) presented within 6 h postoperatively, 26 (37%) between 7 and 24 h and seven (10%) beyond 24 h. CONCLUSION: Patients undergoing anticoagulant or antiplatelet treatment are not a high-risk population for hematoma formation. Forty-seven percent of the patients presented postoperative hematomas beyond 6 h postoperatively, leading to the conclusion that 1-day surgery is not safe.

Trimetazidine reduces renal dysfunction by limiting the cold ischemia/reperfusion injury in autotransplanted pig kidneys.

Ischemia/reperfusion injury leads to delayed graft function, which is a major problem in kidney transplantation. This study investigated the effects of adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was removed and cold-flushed with Euro-Collins (EC), or University of Wisconsin (UW) solutions with or without 10(-6)M TMZ and stored for 48 h at 4 degrees C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Several parameters were analyzed over the 14 d after transplantation. The survival rate was 57% in pigs transplanted with kidneys cold-flushed with UW and 43% for those flushed with EC solution; it was 100% for pigs having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. The functions of the transplanted kidneys were also better preserved after cold flush with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher and the urinary excretion of trimethylamine-N-oxide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infiltrating mononuclear CD45+and CD3+ T cells. These results indicate that the tissue damage due to ischemia/reperfusion injury may be prevented, at least in part, by adding TMZ to preservation solutions.