How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Low Intensity and Frequency Pulsed Electromagnetic Fields Selectively Impair Breast Cancer Cell Viability

<div><p>Introduction</p><p>A common drawback of many anticancer therapies is non-specificity in action of killing. We investigated the potential of ultra-low intensity and frequency pulsed electromagnetic fields (PEMFs) to kill breast cancer cells. Our criteria to accept this technology as a potentially valid therapeutic approach were: <b>1</b>) cytotoxicity to breast cancer cells and; <b>2</b>) that the designed fields proved innocuous to healthy cell classes that would be exposed to the PEMFs during clinical treatment.</p><p>Methods</p><p>MCF7 breast cancer cells and their normal counterparts, MCF10 cells, were exposed to PEMFs and cytotoxic indices measured in order to design PEMF paradigms that best kill breast cancer cells. The PEMF parameters tested were: <b>1</b>) frequencies ranging from 20 to 50 Hz; <b>2</b>) intensities ranging from 2 mT to 5 mT and; <b>3</b>) exposure durations ranging from 30 to 90 minutes per day for up to three days to determine the optimum parameters for selective cancer cell killing.</p><p>Results</p><p>We observed a discrete window of vulnerability of MCF7 cells to PEMFs of 20 Hz frequency, 3 mT magnitude and exposure duration of 60 minutes per day. The cell damage accrued in response to PEMFs increased with time and gained significance after three days of consecutive daily exposure. By contrast, the PEMFs parameters determined to be most cytotoxic to breast cancer MCF-7 cells were not damaging to normal MCF-10 cells.</p><p>Conclusion</p><p>Based on our data it appears that PEMF-based anticancer strategies may represent a new therapeutic approach to treat breast cancer without affecting normal tissues in a manner that is non-invasive and can be potentially combined with existing anti-cancer treatments.</p></div

Are Mixed-Gender Committees Less Biased Toward Female and Male Candidates? An Investigation of Competence-, Morality-, and Sociability-Related Terms in Performance Appraisal

The present research investigated the spontaneous reference to the criteria of competence, morality, and sociability in descriptions made by professional committees evaluating female and male employees’ work performance. We examined whether professional committees used different criteria in their performance appraisal of male and female employees and how gender of committee members influences this outcome. The evidence showed that men were primarily evaluated on the basis of their competence, while women were evaluated on the basis of their performance in all the three (evaluative) criteria. Interestingly, using mixed compared with same gender committee members resulted in higher use of competence-related terms rather than sociability and morality ones, regardless of gender of employees. Overall, the evidence reveals that mixed-gender committees provide similar appraisals of male and female employees based on competence, suggesting that they might be an effective way to reduce gender bias in the performance appraisals

Design and synthesis of the first indole-based blockers of Panx-1 channel

Panx-1 is a membrane channel protein involved in some pathologies such as ischemic stroke, cancer and neuropathic pain, thus representing a promising therapeutic target. We present here a study aimed at obtaining the first class of selective Panx-1 blockers, a new topic for pharmaceutical chemistry, since all compounds used so far for the study of this channel have different primary targets. Among various scaffolds analyzed, the indole nucleous emerged, whose elaboration yielded interesting Panx-1 blockers, such as the potent 5-sulfamoyl derivatives 14c and 15b (I% = 100 at 50 μM). In vivo tests performed in the mouse model of oxaliplatin-induced neuropathy, demonstrated that the hypersensitivity was completely reverted by treatment with 15b (1 nmol, administered intrathecally), suggesting a relationship between this effect and the channel blocking ability. Finally, we decided to perform a virtual screening study on compounds 5b, 6l and 14c using a recently resolved cryo-EM structure of hPanx-1 channel, to try to relate the potency of our new inhibitors. [Display omitted] •Panx-1 is a membrane channel protein connecting the intra and extra cellular space.•The first class of selective Panx-1 blockers with a indole scaffold is described.•In vivo tests performed in the mouse model of oxaliplatin-induced neuropathy.•Molecular modeling using a cryo-EM structure of hPanx-1 channel was performed

Time course in the development of cell death in response to PEMF exposure.

<p>Histograms showing the total number of cells (dark grey) and the total number of dead cells (trypan blue positive, light grey) after 1, 2 or 3 days of daily PEMF exposure (<b>B</b>, <b>D</b>) or in unexposed (control) cultures (<b>A</b>, <b>C</b>). (<b>A</b>, <b>C</b>) Unexposed cultures exhibited a steady increase in bulk cell number during 3 days in culture. (<b>B</b>) Exposure to 3 mT PEMFs for 60 min/day abrogated the typical monotonic increase in total cell number (dark grey) observed in unexposed samples (<b>A</b>) concomitant with an increase in the amount of trypan blue positive cells (light grey) that increased in significance with consecutive daily exposures to PEMFs. The total number of cells in treated samples showed a 40% (+/– 6%) decrease relative to control, whereas trypan blue positive cells increased by 20% (+/– 13%), (total cells in control sample – total cell in treated sample)/total cells in control sample) and (dead cells in control sample – dead cell in treated sample)/dead cells in control sample), respectively. (<b>D</b>) Exposure to 3 mT PEMFs for 90 min/day slowed the increase in total cell number (dark grey) typical of control samples in combination with an increase in the amount of trypan blue positive cells (light grey) that increased in significance with consecutive daily exposures to PEMFs. The total amount of cells in treated sample showed a 20% (+/– 4%) decrease relative to control, whereas trypan blue positive cells increased by 36% (+/– 10%), (total cells in control sample – total cell in treated sample)/total cells in control sample) and (dead cells in control sample – dead cell in treated sample)/dead cells in control sample), respectively. All the values represent the averages of 4 independent experiments with 3 replicates/experiment (n = 12) for the 60-min/day time points and 2 replicates/experiments (n = 8) for 90-min/day time points. P-values, left to right: 0.3246, 0.02032, 0.00004 for 60min/day of exposure and 0.2595, 0.02953, 0.00015 for 90 min/day of exposure.</p

Trypan blue detection of dead cells after exposure to PEMFs for 3 consecutive days.

<p>(<b>A</b>) The percentage dead MCF-7 and MCF-10 cells after exposure to 2, 3 or 5 mT PEMFs at a frequency of 20 Hz for 60 minutes a day for three days. MCF7 breast cancer cell viability was significantly reduced by exposure to PEMFs relative to unexposed samples (controls) or MCF-10 cells (P-values, left to right: 0.02857, 0.00004, 0.02857). (<b>B</b>) Cells treated with PEMFs (3 mT at 20 Hz) for 30, 60 or 90 minutes per day for 3 consecutive days. The histogram depicts the percentage of dead cancer cells relative to unexposed (control) samples (((PEMFs exposed trypan blue positive cells - unexposed trypan blue positive cells)/unexposed trypan blue positive cells))/total cells). Sixty minutes exposures to 3 mT PEMFs significantly increased MCF7 cancer cell death, whereas shorter (30 minutes) or longer (90 minutes) exposure durations exerted smaller effects (P-values, left to right: 0.03175, 0.00004, 0.00015). Values represent the averages of at least 4 independent experiments (n = 4, 12, 4 for 2, 3 and 5 mT, respectively; n =  5, 12, 8 for 30, 60 and 90 minutes, respectively) for MCF7 cells (average ± SD). A total of 5 independent experiments (average ± SD) is provided for MCF-10 cells for all conditions. MCF10 were unresponsive to PEMFs (3 mT, 60 minutes per day for three days) (also see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072944#pone.0072944.s003" target="_blank">Figure S3</a>). 50 Hz PEMFs (3 mT for 60 minutes a day for three days) was less effective at killing MCF-7 cells (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072944#pone.0072944.s002" target="_blank">Figure S2</a>). The potential recovery of MCF-7 cancer cells following PEMF treatment is addressed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072944#pone.0072944.s006" target="_blank">Figure S6</a>.</p

MCF7 and MCF10 cell metabolic status analyzed by IFC at 9 MHz.

<p>(<b>A</b>) Dot plots generated from MCF7 cells after exposure to PEMFs of 2, 3 or 5 mTs and in control (non-exposed) samples and analyzed at a scan frequency of 9 MHz. Exposed samples exhibited a larger right-side population, particularly after exposure to 3 mT PEMFs. (<b>B</b>) Dot plots of MCF7 cells after exposure to 30, 60 or 90 minutes of PEMFs (3 mT, 20 Hz) per day for 3 days; the right-side population was preferentially enhanced in response to 60 minutes exposures. (<b>C</b>) Histograms depicting the percentage increase in the size of the right population normalized to controls after exposure to 2, 3 or 5 mT PEMFs for 60 minutes. Each value is the average of 4 independent experiments (1 replicate/experiment, n = 4) (± SD). P-values, left to right: 0.00879, 0.0017 and 0.07033. (<b>D</b>) Size of right population as a function of exposure duration and normalized to each respective control (unexposed) sample; the right-side population was preferentially enhanced in response to 60 minutes exposures. Each value is the average of 4 independent experiments (1 replicate/experiment, n = 4) (± SD). P-values, left to right: 0.6786, 0.0017 and 1. (<b>E</b>) Dot plots generated from MCF10 cells exposed to 3 mT PEMFs (20 Hz) for 60 minutes/day for three days and in control (unexposed) samples, revealing essentially no change in response to treatment. The dot plots shown were generated from cells of the same experimental date and are representative of cells responses observed in all of the independent experiments with identical conditions. Also see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072944#pone.0072944.s008" target="_blank">Figure S8</a>, for the spread of individual measurements.</p

Box plots depicting the increase in cell death after 1, 2 or 3 days of consecutive PEMF treatment.

<p>(<b>A</b>) 3 mT PEMFs for 60 min/day impaired MCF7 cancer cell viability sufficiently to cause a time-dependent accumulation of compromised cells over the time course of 1 to 3 days. The most significant degree of cell impairment was seen after 3 days (4 independent experiments with 3 replicates/experiment (n = 12)) (p-values, left to right: 0.3246, 0.02032, 0.00004) (also see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072944#pone-0072944-t001" target="_blank">Table 1</a> for the mean, high value, low value and average absolute deviation from median). (<b>B</b>) MCF7 cancer cells treated with 3 mT PEMFs for 90 min/day for 1, 2 or 3 days. Overall, 90 min/day of exposure produced less cytotoxicity than 60 min/day. Data were generated from 4 independent experiments with 2 replicates/experiment (n = 8) (p-values, left to right: 0.2595, 0.02953, 0.00015) (also see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072944#pone-0072944-t002" target="_blank">table 2</a> for the mean, high value, low value and average absolute deviation from median).</p