Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Autophagy and oxidative stress modulation mediate Bortezomib resistance in prostate cancer.

Proteasome inhibitors such as Bortezomib represent an established type of targeted treatment for several types of hematological malignancies, including multiple myeloma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma, based on the cancer cell's susceptibility to impairment of the proteasome-ubiquitin system. However, a major problem limiting their efficacy is the emergence of resistance. Their application to solid tumors is currently being studied, while simultaneously, a wide spectrum of hematological cancers, such as Myelodysplastic Syndromes show minimal or no response to Bortezomib treatment. In this study, we utilize the prostate cancer cell line DU-145 to establish a model of Bortezomib resistance, studying the underlying mechanisms. Evaluating the resulting resistant cell line, we observed restoration of proteasome chymotrypsin-like activity, regardless of drug presence, an induction of pro-survival pathways, and the substitution of the Ubiquitin-Proteasome System role in proteostasis by induction of autophagy. Finally, an estimation of the oxidative condition of the cells indicated that the resistant clones reduce the generation of reactive oxygen species induced by Bortezomib to levels even lower than those induced in non-resistant cells. Our findings highlight the role of autophagy and oxidative stress regulation in Bortezomib resistance and elucidate key proteins of signaling pathways as potential pharmaceutical targets, which could increase the efficiency of proteasome-targeting therapies, thus expanding the group of molecular targets for neoplastic disorders

Free-Floating Iris Pigmented Epithelial Cyst in the Anterior Chamber

An unusual case of a free-floating peripheral pigmented cyst in the anterior chamber is presented. A 30-year-old Caucasian male presented reporting a visual defect on his right eye in prone position over the past year. Slit-lamp examination revealed a small pigmented free-floating peripheral iris cyst at the 6 o’clock position in the anterior chamber. Ultrasound biomicroscopy revealed an unfixed epithelial pigmented cyst with an extremely thin wall and no internal reflectivity. Due to the lack of severity of visual disturbance of the patient, no surgical treatment was indicated. The patient is to be followed up annually and advised to return immediately in case of pain or any visual symptoms. Free-floating iris cysts in the anterior chamber are uncommon and remain stable in the majority of cases. Management includes only regular observation until any complications arise

Chemotactic assay of DU-145 naive and DU-145 RB60 cells using Boyden chambers.

Cells were transferred into a chamber containing serum-free medium with or without Bortezomib. The chambers were placed inside microplates’ wells containing medium supplemented with 20% FBS and left to migrate for 24 h. The DU-145 cells, when exposed to Bortezomib (20 nM), decreased their migration rate. Inhibition of migration was also observed when Bortezomib was added to the lower compartment, indicating a chemorepellent role. The DU-145 RB60 cells were also repelled by Bortezomib (60 nM), while the presence of the drug in the upper compartment induced migration towards the other side of the membrane, where Bortezomib was absent. (TIF)</p

Main cell function assays of naïve DU-145, DU-145 RB60, and DU-145 RB60U cells.

(A, B) Equal numbers of cells were seeded on 24-well plates, and after 24 h of attachment, various doses of Bortezomib (A) or Carfilzomib (B) were added. Following 72 h of incubation, the cells were fixed and subsequently stained with crystal violet. The proliferation rate of naïve DU-145, DU-145 RB60 resistant cells after 24 weeks of drug presence, DU-145 RB60U cells after 24 weeks of drug absence, and DU-145 RB60 cells after 48 weeks of drug presence (60 nM) was assessed by a spectrophotometrical determination of the crystal violet solution’s O.D. at 595 nm. The analysis was performed using the built-in tools provided with the GraphPad Prism 8 software. (C) Cells were transferred into a chamber containing serum-free medium with or without Bortezomib. The chambers were placed inside microplates’ wells containing medium supplemented with 20% FBS and left to migrate for 24 h. The cells crossing the porous filter were then fixed and stained, and after photographing, they were counted using the Cell Counter tool by ImageJ. (D) Cells were seeded on 6-well plates and left to form monolayers. After reaching the desired confluency, wounds were scratched, and the Bortezomib-free media were replaced with medium containing 10% FBS and Bortezomib. The naïve cells were assessed using 20 nM of Bortezomib, and the DU-145 RB60 cells were assessed under the influence of 60 nM Bortezomib. After replacement of the media, photographs were taken, and the wound closure rate was determined by capturing images at the specific time-points of 0, 24, 48, and 72 h. The photographs were analyzed using the ImageJ Manual Wound Healing Size tool and the subsequent analysis was performed using Microsoft Office Excel and GraphPad Prism 8.</p

Effects of Bortezomib on main cell cycle regulators and signaling pathways.

(A) Western blot analyses of key cell cycle proteins p21, p27, and p53 and the proliferation marker PCNA. The experiments were conducted after 24 h of Bortezomib incubation, following a 48 h Bortezomib deprivation of RB60 cells. The + corresponds to the low dose of 20 nM Bortezomib, and the ++ corresponds to the medium dose of 60 nM. The cells were lysed using ice-cold lysis buffer, and protein concentrations were determined using the Bradford assay. The same amounts of total protein were loaded on 12% SDS-PAGE gels, and the transfer was performed using the semidry system. (B) Immunocytochemical staining of naïve DU-145 cells with antibodies against p21 and DAPI to visualize DNA content to assess the localization of p21. Following treatment with 20 nM Bortezomib, the nuclear localization of p21 was verified, indicating the pro-apoptotic role of p21 rather than its pro-survival cytosolic presence. (C) The main pro-survival and proliferation pathways were assessed following the incubation of cells with Bortezomib. All experiments were conducted after 24 h of Bortezomib incubation following a 48-hour drug deprivation from the resistant clones, and the protein quantity was confirmed using the Bradford assay.</p

IC₅₀ Calculation of naïve DU-145, DU-145 RB60, and DU-145 RB60U cells.

The data from crystal violet assays were analyzed using GraphPad Prism 8, and the calculated IC50 values are presented here. The resistant cells exhibited a 5-fold increase in Bortezomib tolerance after 24 weeks of Bortezomib presence, which was augmented more following another 24 weeks of drug presence, reaching a more than 10-fold increase compared to the naïve clone. Additionally, to some extent, cross-resistance to Carfilzomib was observed; the DU-145 RB60 clone achieved 4-fold Carfilzomib resistance compared to the naïve clone after 24 weeks and an almost 6-fold change after another 24 weeks. The long-deprived clone maintained its acquired resistance to both inhibitors during the 24-week monitoring. Regarding resistance to doxorubicin, all three cell clones tested exhibited a similar response to doxorubicin, regardless of resistance to Bortezomib. The experiments were repeated in triplicate, and for the IC50 calculation, the built-in model from GraphPad Prism 8 was used.</p

Wound healing assay of DU-145 naïve and DU-145 RB60 cells.

Cells were seeded on 6-well plates and left to form monolayers. After reaching the desired confluency, wounds were scratched, and the Bortezomib-free media were replaced with medium containing 10% FBS and Bortezomib. The naïve cells were assessed using 20 nM of Bortezomib, and the DU-145 RB60 cells were assessed under the influence of 60 nM Bortezomib. Compared to the control group, the DU-145 naïve cells’ ability to heal wounds was heavily impaired by Bortezomib, while the same effect was not observed on the DU-145 RB60 cells. The resistant cells were able to completely heal the scratches after 72 h of incubation, and the same was achieved by the untreated naïve cells. (TIF)</p