Evolving Trends in the Management of Acute Appendicitis During COVID-19 Waves: The ACIE Appy II Study

Background In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide.


Introduction
COVID-19 pandemic has heavily impacted on surgical services and surgery [1,2]. Since the declaration of pandemic by WHO on the March 12, 2020, 435,626,514 confirmed cases and 5,952,215 deaths have been reported globally [3]. Healthcare systems shifted resources and personnel to manage the increasing number of COVID-19 patients, cancelling or postponing elective operations and outpatient clinics, reducing surgical beds as a tailored strategy to avoid unnecessary resource consumption and mitigate the risk of SARS-COV-2 infection in surgical patients [4]. In urgent surgical diseases, such as acute cholecystitis, acute diverticulitis and acute appendicitis (AA), national and international surgical societies recommended to improve non-operative management (NOM), whenever applicable, avoiding admission in the hospital and supporting alternative strategies such as phone and remote-follow-up [5][6][7][8].
In 2020, the ''Association of Italian Surgeons in Europe'' (Associazione Chirurghi Italiani in Europa, ACIE) explored the global attitudes in the management of AA on an international cohort of 709 surgeons in the Appy study [9], showing a statistically significant shift toward NOM during the first phase of the outbreak in comparison with the pre-pandemic period (23.7 and 5.3 percent vs. 6.6 and 2.4 percent, respectively, both P \ 0.001) with one-third of respondents moving toward open surgery in line with the initial recommendations/guidelines released in the early stages of the pandemic.
With the evolution of pandemic and a major knowledge of the disease, several strategies are now in place to mitigate the risk and might have produced an important effect in the management of AA, still the most common surgical abdominal emergency with a long-life risk of 8-9% [10].
In the present study (ACIE Appy II), we surveyed the same sample of surgeons to explore if any differences occurred in the management of AA in the last waves of pandemics during 2021.

Method
A follow-up internet-based survey based on a previous research project [9] from the ACIE study group was carried out to investigate the impact of the COVID-19 pandemic over the clinical decision for patients with AA, one year after the beginning of the pandemic. An online questionnaire was sent to all 709 participants of the ACIE Appy study by email (Appendix 2). The data sampling collected information from Surgical trainees or certified Surgeons across Europe, Asia, Africa, Oceania, North and South America. The purpose of the study was communicated beforehand to each participant, whose enrollment was voluntary as no incentives were offered to collaborate with the study.

Questionnaire development and composition
Based on the previously used strategy [9], the components and topics for the questionnaire were developed by the steering committee using web-based and remote discussion. The technical functionality of the electronic questionnaire was tested before sending the invitations. Names, locations, and baseline information were stored with the questionnaire. Once an agreement was reached, the questionnaire was completed using Google Form [The COVID-19 Appy-2 Study Form] survey software (Google LLC, Mountain View, California US).
The questionnaire included 5 Sections, with 36 closedended questions in total. The first three sections included general questions about the hospital organization and screening policies; personal protective equipment and personal attitudes about the management of AA. The fourth and fifth ones focused on the real-life analysis of patient presentation and management strategies of patients with AA one year after the beginning of the COVID-19 pandemic.
Uncomplicated appendicitis was defined as appendicitis without abscess, whereas complicated appendicitis included the presence of an intraabdominal abscess or free perforation with diffuse peritonitis. Non-operative management (NOM) was defined as conservative management with antibiotics; this could include percutaneous abscess drainage.
The list of alternatives for every single quantitative question included a percentage category as follows: ''B 25%'', ''26-50%'', ''51-75%'', ''76-100%''. The steering committee decided to use ranges of predetermined percentages in order to allow an easier aggregation and analysis of the information collected.
The estimated time to complete the survey was 8-10 min. The aim was to define the status of the management of AA one year after the beginning of the pandemic as compared with the pandemic period.

Study circulation
From August 15, 2021, the questionnaire was online and open to completion until September 30, 2021. The link was sent to all 709 ACIE Appy participants by email. Two other remainders were sent, always by email, to maximize the response rate.

Data handling and extraction
A member of the steering committee (MP) downloaded the questions and shared them with the other members for data analysis and discussion. Multiple entries from the same individual or members of the same surgical unit were manually searched and eliminated if contradictory findings were observed.

Statistical analysis
Descriptive data are presented as numbers and proportions for categorical variables. Contingency tables and the Chisquare test were used for the comparisons. Statistical analyses were performed in Stata version 16.0 (StataCorp), and nominal two-sided P \ 0.05 values were considered statistically significant.

Baseline information
Overall, in 2021, 476 answers (response rate 67.1%) were received from 59 Countries. Most respondents were from countries that were the most affected at the time of the first wave of the pandemic and collaborate with the previous survey. A total of 189 answers (39.7%) were returned from Italy and 64 (13.4%) from Spain, summing together about half of the answers received.

Hospital organization and screening policies
Baseline characteristics of included hospitals in 2021 were comparable to those included in the previous survey from 2020 with 91.8% hospitals attending COVID-19 patients and 8.1% not specifically treating COVID-19 patients ( Table 1). The screening policy in 2021 showed significant differences in comparison with 2020 with a higher percentage of systematic SARS-CoV-2 screening for all patients with AA (89.5% vs. 37.4%, P \ 0.001) ( Fig. 1) and not only to symptomatic subjects. Moreover, the number of patients screened exclusively with PCR and antigenic tests in 2021 was significantly higher in comparison with 2020 (74.1% vs. 26.3%, P \ 0.001) when 66.7% of patients were screened with a chest X-ray or computed tomography (CT) in addition to PCR or serological tests (Fig. 2).

Personal protective equipment (PPE)
The survey on changes in the use of PPE showed that in 2021, a higher number of surgeons started to use no specific personal protective devices (12.2% vs. 0% P \ 0.001), even in untested patients (2.9% vs. 0%, P \ 0.001) ( Table 2) in comparison with 2020. Conversely, in COVID-19 positive patients, specific personal   Personal attitude: operative versus non-operative management of acute appendicitis In patients with uncomplicated appendicitis (no right iliac fossa abscess), in 2021, a higher percentage of surgeons did not change their attitude in the management of these patients (55.7% vs. 42.5%, P \ 0.001) ( Table 3), whereas 13.9% still admitted changing their treatment strategy, especially in COVID-19 positive or untested patients (30.5%) (Fig. 3). The rate of subjects treated with NOM significantly decreased (14.3% vs. 23.7%, P \ 0.001), whereas there was a significant raise in the number of surgeons performing straightforward laparoscopic appendectomy (39.3% vs. 22.4%, P \ 0.001).
In case of appendicitis complicated by right iliac fossa abscess, once again, in 2021, a higher percentage of surgeons did not change their attitude in the management of these patients (67.9% vs. 47.4%, P \ 0.001). Additionally, similarly to uncomplicated appendicitis, the rate of subjects treated with NOM significantly decreased (20% vs. 32.7%, P \ 0.001), while surgeons tended to perform more straightforward laparoscopic appendectomy (64.9% vs. 33.5%, P \ 0.001).

Personal attitude: surgical approach
In 2021, surgeons tended to change less frequently their standard surgical approach (86.8% vs. 61.1%, P \ 0.001) from laparoscopic to open or vice versa than in 2020 (Table 4).
If a laparoscopic appendectomy was performed, a higher number of survey respondents in 2021 stated not to use specific smoke filter system (31.7% vs. 25.8%, P \ 0.001). However, when such kind of devices were used, they were more frequently represented by commercially available systems (64.6% vs. 56.3%, P \ 0.001) than homemade package.

Changes in patient presentation from 2020 to 2021 at participants Institutions
In 2021, there was a higher percentage of patients with AA that tested positive for SARS-CoV-2 before or after surgery (P \ 0.001) ( Table 5).
Respondents from 2021 tended to use less frequently a NOM and send patients home in uncomplicated appendicitis than those from 2020 (P \ 0.001 and P = 0.007, respectively). Conversely, more patients with complicated appendicitis were treated with conservative treatment with antibiotics ± percutaneous drainage (P = 0.002) (Fig. 4).

Discussion
Our study revealed some attitudinal changes in the management of AA in 2021 in comparison with the first waves of pandemic in 2020. Improvement of the knowledge of SARS-CoV-2 infection, a timely healthcare systems' response in term of screening and a wider availability of

Local policies and screening
Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic tests as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery, but this could reflect a systematic screening of patients admitted in the hospital, not possible for reduced availability of diagnostic tests in the first months of the pandemic, where half of the responders screened only patients suspected or with respiratory symptoms. Because COVID-19 patients undergoing surgery have an estimated mortality of 23.8% and a 51.2% of pulmonary complications [11], a patient with AA tested positive for SARS-CoV-2 may benefit from a NOM trial to avoid surgery.

Open versus laparoscopic appendicectomy
During the first wave of the pandemic, in the perspective of a short-term outbreak and due to the concern potential spreading of SARS-COV-2 particles by smoke plumes and pneumoperitoneum during laparoscopy, open surgery was initially suggested by some surgical societies and some authors [12][13][14][15]. The effect was evident in our previous study, with one third of responders moving toward an open approach. Although SARS-COV-2 RNA has been detected in the peritoneal fluid [16,17] and transmission is biologically plausible [18], no case of transmission by laparoscopy has been reported. Moreover, smoke plumes evacuation might be more challenging in open surgery and several homemade and commercial ultrafiltration systems are now available to err on the side of safety [19][20][21][22], although some of these systems may be time and costconsuming, especially in emergency surgery by an already stretched staff [23]. While 68.2% of responders use ultrafiltration system during laparoscopic appendicectomy systematically or in COVID-19 patients, one third of responders (31.7%) declare not to use ultrafiltration device during laparoscopy, and this percentage was higher than in previous study (31.7% vs. 25.8%). This may reveal a reduced perceived risk of transmission associated to minimally invasive surgery or a low estimate of these devices as crucial mitigation strategy in operative room. Laparoscopic appendicectomy is now unanimously recommended for its advantages, including shorter recovery time, better diagnostic accuracy and the possibility to be performed as ambulatory appendectomy [24][25][26] to reduce the risk of system overburden. In the light of the long-term pandemic, a 30% of recurrence in the NOM patients as reported by the CODA trial [27] may represents a further point in favor of laparoscopy, reducing costs and risk of SARS-CoV-2 exposure in patients attending emergency department [28]. In comparison with the previous survey, the proportion of centers performing 76-100% of appendicectomy by open approach declined significantly moving from 22.5 to 10.9%, a percentage similar to the declared 9.1% of pre-pandemic times [9].

Non-operative management (NOM)
The pandemic scenario has had a major impact on presentation rate and strategies of AA worldwide. A metaanalysis on this topic [29] showed a significatively increased use of conservative management of AA in all ages during the outbreak than before. Especially in the more troublesome times of pandemic, NOM remained a reasonable option in patients with AA, with fewer complications and shorter length of stay [30,31] although with a low effective rate than surgery [32]. In a recent metaanalysis on the role of NOM in the COVID-19 era including 2140 patients, 44.8% of patients had a trial of NOM, with a failure rate of 16.4% and a complication rate of 4.5% with no mortality [33].
Interestingly, only 10.5% of respondents used NOM in more than half (51-100%) of cases with uncomplicated AA, a twofold reduction in comparison with the 23.6% of the previous study. This change may reflect a shift toward the use of laparoscopic appendicectomy as the first option, due to its superiority in the definitive control of the disease [34,35], a better organization of the healthcare systems and less concern about the risk of viral spreading by minimally invasive surgery.

Appendicular abscess
A higher rate of complicated appendicitis during pandemic have been reported by several authors [36][37][38]. However, due to the decrease in the overall number of cases, this might be related to a prehospital selection bias: as many cases of uncomplicated AA probably settled outside the hospital by antibiotic or spontaneously [39] the rate of those decreased, while complicated AAs are admitted at the same number with an apparent increase in their rate. NOM may be an option in case of appendicular abscess with a failure rate of 7.4% and the need for percutaneous drain in 19.8%. However, laparoscopy shows the best outcomes in terms of readmission and reintervention [40]. Only 22.8% of responders applied NOM ± percutaneous drainage strategy in appendicular abscess versus the 38.1% from the previous study. These may reflect again an implementation of surgical system response to pandemic, despite the increasing number of AA treated, as the 84.1% of centers declares to treat 5-20 cases per month versus 49.9% in 2020.

Study limitations
This study presents some limitations. For a fair comparison, we used the same self-selected sample of the first study: the missed participation in the first survey by surgeons as their countries were marginally interested by the first COVID-19 waves did not consent their participation in the present study, introducing a selection bias. However, most of the respondents were from countries (Italy, Spain) heavily impacted by all pandemic waves, so that important data about the change in clinical decision-making in the management of acute appendicitis during the different phases of pandemic can be obtained. To keep pragmatic the design of the study, we did not investigate about SARS-CoV-2 vaccination among responders and patients treated, so that important information about the system response in 2021 was not captured. To our knowledge, this is the first survey re-evaluating for the second time the changes in the attitudes in the management of AA occurred in the COVID-19 pandemic worldwide.  Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons. org/licenses/by/4.0/.