COVID-19 infection has shown rapid growth worldwide, and different therapies have been proposed for treatment, in particular, the combination of immune response modulating drugs such as chloroquine and hydroxychloroquine (antimalarials) alone or in combination with azithromycin. Although the clinical evidence supporting their use is scarce, the off label use of these drugs has spread very quickly in face of the progression of the epidemic and the high mortality rate in susceptible populations. However, these medications can pathologically prolong the QT interval and lead to malignant ventricular arrhythmias such that organized guidance on QT evaluation and management strategies are important to reduce morbidity associated with the potential large-scale use.
Background
The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies.
Methods
GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1–10; 11–15; 16–20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values.
Discussion
HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years.
Trial registration
EudraCT number: 2019–004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).
Post-prandial hypotension is a common finding in this elderly population. We did not find distinctive conditions or markers that allow identification of subjects at risk for postprandial hypotension and its complications. This should prompt for routine screenings in specialized facilities to prevent complications.
Head-up tilt table testing (HUTT) is a useful tool for the diagnosis of unknown origin of syncope. A setback is its duration. This study tries to establish a specific parameter that, according to the heart rate elevation in the test's initial phase, allows a reliable prediction of its outcome. In a prospective study, every patient being under unknown syncope workup was included. A two-phase 20-minute tilt table test was performed. The initial phase was passive, and the second required pharmacological stimulation with isoproterenol. The basal and 5- and 10-minute heart rate values of the passive phase were measured and compared within the group and against negative tests. During a 1-year period, 115 HUTT were performed: 88 were positive and 27 negative. The negative HUTT patients had an increase in HR of 5.05 (+/- 13.5) beats/min at 5 minutes, and 5.79 (+/- 12.9) beats/min at 10 minutes (P = 0.2). Those with a positive HUTT had an increase of 9.05 (+/- 14.5) beats/min at 5 minutes, and of 10 (+/- 13.4) beats/min at 10 minutes (P < 0.001). There were no significant changes in HR when comparing positive to negative HUTT. There is no specific number that allows predication of outcome early in HUTT. Within the group, variations are important. Only a group tendency can be established, which strongly correlates with the results obtained during the test.
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