Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...

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Lead ions (Pb) possess characteristics similar to Ca. Because of this and its redox capabilities, lead causes different toxic effects. The neurotoxic effects have been well documented; however, the toxic effects on cardiac tissues remain allusive. We utilized isolated guinea pig hearts and measured the effects of Pb on their contractility and excitability. Acute exposure to extracellular Pb had a negative inotropic effect and increased diastolic tension. The speed of contraction and relaxation were affected, though the effects were more dramatic on the speed of contraction. Excitability was also altered. Heart beat frequency increased and later diminished after lead ion exposure. Pro-arrhytmic events, such as early after-depolarization and a reduction of the action potential plateau, were also observed. In isolated cardiomyocytes and tsA 201 cells, extracellular lead blocked currents through Cav1.2 channels, diminished their activation, and enhanced their fast inactivation, negatively affecting their gating currents. Thus, Pb was cardiotoxic and reduced cardiac contractility, making the heart prone to arrhythmias. This was due, in part, to Pb effects on the Cav1.2 channels; however, other channels, transporters or pathways may also be involved. Acute cardiotoxic effects were observed at Pb concentrations achievable during acute lead poisoning. The results suggest how Cav1.2 gating can be affected by divalent cations, such as Pb, and also suggest a more thorough evaluation of heart function in individuals affected by lead poisoning.

Her research interests include molecular evolution of human pathogens and their epidemiology.

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