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. 2024 Mar 18;19(3):e0297985. doi: 10.1371/journal.pone.0297985

Air enema reduction versus hydrostatic enema reduction for intussusceptions in children: A systematic review and meta-analysis

Lan Liu 1,#, Ling Zhang 1,#, Yifan Fang 1,#, Yingying Yang 1, Wen You 1, Jianxi Bai 1, Bing Zhang 1, Siqi Xie 1,*, Yuanyuan Fang 1,*
Editor: Ozlem Boybeyi-Turer2
PMCID: PMC10947698  PMID: 38498581

Abstract

Objectives

We conducted a comprehensive meta-analysis to compare the effectiveness and safety of fluoroscopy-guided air enema reduction (FGAR) and ultrasound-guided hydrostatic enema reduction (UGHR) for the treatment of intussusception in pediatric patients.

Methods

A systematic review and meta-analysis were conducted on retrospective studies obtained from various databases, including PUBMED, MEDLINE, Cochrane, Google Scholar, China National Knowledge Infrastructure (CNKI), WanFang, and VIP Database. The search included publications from January 1, 2003, to March 31, 2023, with the last search done on Jan 15, 2023.

Results

We included 49 randomized controlled studies and retrospective cohort studies involving a total of 9,391 patients, with 4,841 in the UGHR and 4,550 in the FGAR. Specifically, UGHR exhibited a significantly shorter time to reduction (WMD = -4.183, 95% CI = (-5.402, -2.964), P < 0.001), a higher rate of successful reduction (RR = 1.128, 95% CI = (1.099, 1.157), P < 0.001), and a reduced length of hospital stay (WMD = -1.215, 95% CI = (-1.58, -0.85), P < 0.001). Furthermore, UGHR repositioning was associated with a diminished overall complication rate (RR = 0.296, 95% CI = (0.225, 0.389), P < 0.001) and a lowered incidence of perforation (RR = 0.405, 95% CI = (0.244, 0.670), P < 0.001).

Conclusion

UGHR offers the benefits of being non-radioactive, achieving a shorter reduction time, demonstrating a higher success rate in repositioning in particular, resulting in a reduced length of postoperative hospital stay, and yielding a lower overall incidence of postoperative complications, including a reduced risk of associated perforations.

Introductions

Intussusception stands as the most prevalent etiology of intestinal obstruction in pediatric patients. A substantial majority, approximately 75–90%, exhibit no identifiable cause and are classified as idiopathic intussusception [1–4]. This condition primarily affects the small intestine, with infrequent occurrences in the large intestine [5]. Clinical presentation typically encompasses symptoms such as abdominal pain, vomiting, and hematochezia, although the classic triad of symptoms is encountered in less than 25% of cases [6,7]. Historically, fluoroscopy-guided air enema reduction (FGAR) has served as the primary therapeutic modality for intussusception. Its prominence stems from the demonstrated efficacy and safety of enema decompression established during the 1940s and 1950s. In recent years, ultrasound-guided hydrostatic enema reduction (UGHR) has gained traction as a non-invasive, radiation-free imaging technique [8–10]. The advent of UGHR in clinical practice traces its origins back to 1982 when Kim et al. [11] first reported successful reduction of ileocolonic intussusception using warm saline enema under real-time ultrasound guidance. This approach has progressively gained popularity and involves ultrasound confirmation of the intussusception’s location. A predetermined initial pressure is established, followed by ultrasound-guided injection of warm saline into the intestinal tract. Successful reduction is verified when saline flows into the intestinal tract from the ileocecal region, resulting in the manifestation of characteristic signs such as the “crab claw sign” and “honeycomb sign” [12]. Although numerous studies have indicated that UGHR has advantages such as a higher success rate of resetting, greater safety, and radiation-free procedures, these merits are considered worthy of implementation in clinical practice. However, some studies also suggest that FGAR, as a traditional treatment method, remains practical in clinical settings due to its simplicity, ease of execution, and shorter learning curve. Besides, despite the burgeoning utilization of UGHR, a notable gap persists in terms of comprehensive, large-scale systematic comparisons and analyses assessing the efficacy, safety, and long-term prognostic implications of FGAR versus UGHR. We conducted a comprehensive meta-analysis comparing the efficacy and safety of air enema reduction and hydrostatic enema reduction for the treatment of childhood intussusception. Through an extensive literature search and rigorous clinical data analysis, our study aims to present a more secure and dependable therapeutic alternative for children with intussusception, thereby furnishing clinicians with compelling diagnostic and treatment evidence.

Methods

Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [13] (S1 Checklist). We registered the study on PROSPERO, of which the registration number was CRD42023414518.

We conducted a systematic review of studies published in PUBMED, Google Scholar, MEDLINE, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database. The search has a limit on date from Jan 1, 2003 to Mar 31, 2023, with the last search done on Jan 15, 2023. No publication restrictions or study design filters were applied. We formulated the search strategy, inclusion criteria and exclusion criteria according to the PICOS principles: (1) Type of study: randomized or non-randomized controlled trial, with the language limited to Chinese and English; (2) Participants of the study: pediatric patients (aged <18 years) who underwent enemas due to intussusception; (3) Interventions adopted: fluoroscopic air enema or ultrasound-guided saline enemas were used; (4) The main outcome indicators: time to reset, success rate of reset, recurrence rate, and occurrence of postoperative complications; (5)The search strategy for those databases was as follows: ((enema [Title/Abstract]) AND (intussusceptions [Title/Abstract])), hydrostatic enema for intussusceptions, ((enema [Title/Abstract]) AND (intussusceptions [Title/Abstract])) AND (ultrasound [Title/Abstract]), Reference lists from related articles were also scanned to broaden the search. A hand search was performed in all six databases.

Inclusion criteria were applied as follows: (1) confirmation of intussusception diagnosis; (2) subjects aged below 18 years; (3) availability of relevant outcome measures, such as patient numbers, study design, clinical symptomatology, reset success rates, complications, and recurrence; (4) provision of suitable statistical estimates or counts; and (5) comparative investigations involving both fluoroscopy-guided air enema reduction and ultrasound-guided hydrostatic enema reduction.

Exclusion criteria were applied as follows: (1) case reports involving fewer than five cases; (2) subjects exceeding 18 years of age; (3) articles categorized as reviews or meta-analyses; (4) conference abstracts; (5) articles with insufficient data; (6) cases included that did not pertain to acute intussusception or were combined with secondary intussusception; and (7) studies lacking a direct comparison between fluoroscopy-guided air enema reduction and ultrasound-guided hydrostatic enema reduction.

The following data were extracted: the first author’s name, year of publication, study type, mean age, gender distribution, patient count, primary clinical symptoms, time required for reduction, reset pressure applied, reset success rate, duration of occult blood in stool, time until recovery of bowel function, length of hospital stay, recurrence rate, and complications.

The quality assessment of randomized controlled studies (RCTs) was conducted using the Cochrane Collaboration’s Risk of Bias tool [14]. Only studies with low or unclear risk of overall bias were included in the meta-analysis. Non-randomized studies underwent assessment with the Newcastle-Ottawa Scale (NOS) [15]. The NOS score, ranging from 0 to 9 stars, evaluates studies across three categories: selection, comparability, and outcome/exposure. Studies with a NOS score of ≥6 stars were deemed high quality and incorporated into our analysis. The literature retrieval and data collection were to be carried out by at least two researchers. They independently read the titles and abstracts of the literature, excluding those that were not relevant to the content of this study. Subsequently, they will carefully read the full texts according to inclusion and exclusion criteria, extracting relevant information. In case of disagreements, resolution will be sought through negotiation, or a third researcher may be consulted for assistance in making a judgment.

Statistical analysis was conducted by STATA version 16.0 and RevMan version 5.2. Relative risk (RR) was applied for dichotomous variables, and weighted mean difference (WMD) was applied for continuous variables. Some study outcomes were reported as medians with ranges or mid-quartiles with ranges. According to the methods introduced by Luo et al. [16] and Wan et al. [17], those data were converted to means with deviations, thus the results for each group are presented as the mean ± standard deviation (x± s). The I2 statistic was used to test the degrees of heterogeneity, the P-value of I2 < 0.05 was used to indicate high heterogeneity and vice versa. The random-effects model was applied to pool the high heterogeneity results and the fixed-effects model was used for low heterogeneity (P-value of I2 > 0.05; Table 2A and 2B). Begg’s Test and Egger’s Test were performed to assess the risk of bias (Table 3), while Begg’s funnel plots were applied. P < 0.05 was considered to be statistically significant in the text.

Table 2. Pooled proportions of clinical characteristics for dichotomous variables (A). Pooled proportions of clinical characteristics for continuous variables (B).

Outcome Number of studies Participates (n) Total number of cases (N) Statistical results Heterogeneity Analysis model
U F U F Statistic Value(95%CI) P value I2 (%) P value
Male 45 2839 2712 4447 4204 RR 0.994(0.964,1.026) 0.718 0.00 0.988 Fixed
Female 45 1608 1492 4447 4204 RR 1.010(0.955,1.069) 0.720 0.00 0.993 Fixed
Paroxysmal crying or Abdominal pain 18 1446 1322 1741 1616 RR 1.031(0.995,1.068) 0.096 32.30 0.098 Fixed
Vomiting 17 1335 1216 1718 1594 RR 0.969(0.928,1.011) 0.149 0.00 0.624 Fixed
Abdominal mass 13 590 692 820 935 RR 1.007(0.938,1.081) 0.852 0.00 0.594 Fixed
Bloody stool 17 622 632 1696 1571 RR 0.963(0.855,1.085) 0.536 55.80 0.003 Random
Success rate of reset 48 4518 3766 4722 4305 RR 1.128(1.099,1.157) <0.001※ 71.40 <0.001※ Random
Recurrence 25 186 293 3134 2680 RR 0.391(0.269,0.569) <0.001※ 51.50 0.002 Random
Total complications 20 58 195 1349 1225 RR 0.296(0.225,0.389) <0.001※ 13.30 0.288 Fixed
Perforation 23 13 43 2376 2381 RR 0.405(0.244,0.670) <0.001※ 0.00 0.968 Fixed
Vomiting 10 14 32 619 563 RR 0.463(0.271,0.791) 0.050 0.00 0.825 Fixed
Diarrhea 9 13 43 558 507 RR 0.318(0.182,0.558) <0.001※ 0.00 0.948 Fixed
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RR, relative risk; CI, confidence interval; U, ultrasound-guided hydrostatic enema reduction; F, fluoroscopy-guided air enema reduction; ※, P < 0.05 was considered to be statistically significant.

WMD, weighted mean difference; CI, confidence interval; U, ultrasound-guided hydrostatic enema reduction; F, fluoroscopy-guided air enema reduction; ※, P < 0.05 was considered to be statistically significant.

Table 3. Begg’s and Egger’s test of publication bias of clinical characteristics.

Outcome Number of studies P-valuea
Begg’test Egger’test
Gender
Male 45 0.883 0.388
Female 45 0.604 0.117
Age 45 0.087 0.893
Duration of onset 29 0.003* 0.485
Clinical symptoms
Paroxysmal crying or abdominal pain 18 0.127 0.025
Vomiting 17 0.753 0.462
Abdominal mass 13 1.000 0.607
Bloody stool 17 0.174 0.249
Ending indicators
Resetting time 31 0.248 0.004*
Resetting pressure 4 0.734 0.378
Success rate of reset 48 0.001* 0.000*
Duration of occult blood in stool 7 0.764 0.811
Length of hospitalization 18 0.069 0.676
Recurrence 25 0.216 0.618
Complications
Total complications 20 0.456 0.845
Perforation 23 0.128 0.236
Vomiting 10 0.371 0.795
Diarrhea 9 0.348 0.166
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a: P value means the value of Pr>|z| (continuity corrected, in Begg’s Test) or P>|t| (in Egger’s Test)

*:P value < 0.05 was considered to have a high risk of publication bias.

Results

We initially identified 1231 articles through our comprehensive literature search. Prior to screening, 986 records were expunged from consideration. Subsequently, after the removal of duplicate entries, an additional 119 records were excluded following a meticulous full-text review, as they failed to satisfy our predefined inclusion criteria (Fig 1). Ultimately, our analysis encompassed a total of 49 studies mostly from the Asia and Europe, involving 9391 patients, with 4841 in the ultrasound-guided hydrostatic enema reduction group (UGHR) and 4550 in the fluoroscopy-guided air enema reduction group (FGAR).

Fig 1. Flow diagram representing the selection of study.

Fig 1

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Characteristics and risk of bias of included studies

The baseline characteristics of the 49 records, including first author, publication year, study type, number of patients, male/female sex ratio, and age of operation, are presented in Table 1.The NOS scores ranged from 6 to 8 stars, reflecting the quality of the non-randomized controlled studies (case-control and cohort studies) (S1 Table), and S1A and S1B Fig presents the Cochrane Collaboration’s Risk of Bias Tool for the randomized controlled studies (RCTs) that were judged to have a low risk of bias. Table 2(A) and 2(B) show the overall analyses for dichotomous and continuous variables, respectively.

Table 1. Baseline characteristics of 49 records with 9391 patients enrolled in the meta-analysis.

Name Year Study type Number of patients Gender(male/female) Age(m)
U F U F U F
Wang et al [18] 2013 RCT 46 46 38/8 40/6 15±5.04 14.16±10.2
Zhang et al [19] 2014 RCT 64 64 42/22 40/24 5.89±1.12 6.03±1.34
Guo et al [20] 2014 R 352 230 198/154 152/78 3–132 3–60
Yi et al [21] 2015 RCT 39 39 25/14 26/13 24.24±8.16 23.76±10.68
Zhong et al [22] 2015 RCT 44 40 ‘32/12 27/13 14.4±1.32 10.8±1.44
Wu et al [23] 2015 R 45 42 30/15 28/14 9.5±3.9 9.3±3.5
Li et al [24] 2015 R 76 73 51/25 49/24 14.4±6 13.2±7.2
Jiang et al [25] 2016 RCT 74 74 40/34 39/35 33.6±18 34.8±15.6
Liao et al [26] 2016 RCT 30 29 14/16 18/11 12.6±4.92 12.72±2.28
Yang et al [27] 2016 RCT 50 50 36/14 35/15 9.6±2.4 9.9±2.4
Deng et al [28] 2016 RCT 45 45 28/17 30/15 8.8±3.6 8.9±3.8
He et al [29] 2017 RCT 60 60 32/28 31/29 36±18 36±14.4
Xu et al [30] 2017 R 126 120 67/53 65/55 31.2±16.8 32.4±16.8
Zhang et al [31] 2017 RCT 34 34 N N N N
Xie et al [32] 2017 RCT 62 62 40/22 42/20 23.52±6.29 20.67±4.14
Wang et al [33] 2018 R 406 417 298/108 305/112 9.5±1.7 11.3±4.5
Yu et al [34] 2018 R 45 45 22/23 23/22 30.72±7.32 30.72±6.48
Wu et al [35] 2018 RCT 62 62 N N N N
Pan et al [36] 2018 R 373 262 223/150 168/94 13.1±7.3 12.6±6.7
Deng et al [37] 2018 RCT 80 80 61/19 55/25 10.15±4.75 9.93±4.75
Zhang et al [38] 2018 R 45 46 23/22 25/21 3.54±1.44 3.59±1.48
Zhou et al [39] 2019 RCT 41 41 23/18 25/16 10.11±4.15 10.77±4.85
Zhao et al [40] 2019 RCT 37 37 20/17 21/16 10.5±4.8 10.2±5.0
Wang et al [41] 2019 RCT 30 30 21/9 18/12 26.9±19.7 24.8±13.7
Jiang et al [42] 2019 R 58 58 N N N N
Wang et al [43] 2019 RCT 50 50 28/22 27/23 21.48±7.56 17.4±9.96
Zhang et al [44] 2020 R 50 48 37/13 24/14 14.15±6.55 14.57±7.09
Guo et al [45] 2020 R 38 38 20/18 17/21 20.4±13.44 19.8±12.36
Wang et al [46] 2020 R 240 192 N N 24.00±9.71 20.16±4.10
Li et al [47] 2020 RCT 45 45 28/17 26/19 29.73±7.91 31.24±8.59
Qi et al [48] 2020 RCT 35 35 20/15 21/14 19.08±3.12 18.6±2.76
Sui et al [49] 2021 R 105 104 77/28 68/36 87±13.08 83.64±15.84
Cai et al [50] 2021 RCT 23 22 12/11 12/10 1.62±0.45 1.59±0.45
Ding et al [51] 2021 RCT 31 31 21/10 20/11 15.66±2.73 19.45±2.37
Zhang et al [52] 2021 RCT 76 72 45/31 49/23 42.24±7.32 40.80±6.48
Chen et al [53] 2021 R 42 42 23/19 22/20 11.76±5.04 11.4±4.92
Lian et al [54] 2021 RCT 49 49 27/22 29/20 20.16±6.6 19.92±7.56
Chen et al [55] 2021 RCT 40 40 23/17 24/16 12.36±3.96 12.24±3.96
Du et al [56] 2021 R 45 42 29/16 27/15 13.65±4.27 14.78±5.02
Pei et al [57] 2021 R 43 43 25/18 24/19 22.33±4.55 21.09±4.38
Liu et al [58] 2021 P 1119 1005 731/388 670/335 24.38±23.78 25.80±21.99
Yang et al [12] 2021 R 119 245 89/30 163/82 25.13±2.03 22.47±1.52
Han et al [59] 2022 RCT 90 90 68/22 54/36 8.3±1.6 8.5±1.7
Liu et al [60] 2022 RCT 35 35 20/15 19/16 37.01±3.24 36.01±3.31
Lv et al [61] 2022 R 43 37 30/13 23/14 12.01±1.20 11.82±0.92
Liu et al [62] 2022 RCT 58 58 31/27 30/28 16.23±1.85 15.26±2.05
Pu et al [63] 2022 RCT 75 75 46/29 45/30 12.32±3.15 12.23±3.12
Chukwu et al [64] 2022 RCT 26 26 16/10 19/7 5.5±1.8 6.1±1.6
Lian et al [65] 2023 RCT 40 40 29/11 27/13 13.68±10.01 13.03±7.33
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R, retrospective cohort study; RCT, randomized controlled trial study; P, prospective cohort study; N: Not reported; m: Month; U, ultrasound-guided hydrostatic enema reduction; F, fluoroscopy-guided air enema reduction.

Comparations and outcomes of the meta-analysis

Age of operation

Forty-five studies contributed data about UGHR and FGAR, including 8501 patients (4335 in the UGHR and 4166 in the FGAR, Table 2(B)). Random-effects model was applied because of significant heterogeneity (I2 = 90.00%, P < 0.001 Table 2(B)). Meta-analysis showed no significant difference between the two groups [WMD = 0.379, 95% CI = (-0.128,0.885), P = 0.143 > 0.05].

Duration of onset

Twenty-nine studies contributed data about UGHR and FGAR, including 3741 patients (1961 in the UGHR and 1780 in the FGAR, Table 2(B)). Random-effects model was applied because of significant heterogeneity (I2 = 97.00%, P < 0.001 Table 2(B)). Meta-analysis showed no significant difference between the two groups [WMD = -0.296, 95% CI = (-1.788,1.197), P = 0.698 > 0.05].

Clinical symptoms

Clinical symptoms reported in the studies primarily encompassed paroxysmal crying or abdominal pain, vomiting, the presence of an abdominal mass, and the passage of bloody stools.

Paroxysmal crying or abdominal pain: Eighteen studies contributed data about UGHR and FGAR, including 2768 patients (1446/1741 in the UGHR and 1322/1616 in the FGAR, Table 2(A)). Fixed-effects model was applied because of low heterogeneity (I2 = 32.30%, P = 0.098 Table 2(A)). Meta-analysis showed no significant difference between the two groups [RR = 1.031, 95% CI = (0.995,1.068), P = 0.096 > 0.05].

Vomiting: Seventeen studies contributed data about UGHR and FGAR, including 2551 patients (1335/1718 in the UGHR and 1216/1594 in the FGAR, Table 2(A)). Fixed-effects model was applied because of low heterogeneity (I2 = 0.00%, P = 0.624 Table 2(A)). Meta-analysis showed no significant difference between the two groups [RR = 0.969, 95% CI = (0.928,1.011), P = 0.149 > 0.05].

Abdominal mass: Thirteen studies contributed data about UGHR and FGAR, including 1282 patients (590/820 in the UGHR and 692/935 in the FGAR, Table 2(A)). Fixed-effects model was applied because of low heterogeneity (I2 = 0.00%, P = 0.594 > 0.05 Table 2(A)). Meta-analysis showed no significant difference between the two groups [RR = 1.007, 95% CI = (0.938,1.081), P = 0.852 > 0.05].

Bloody stool: Seventeen studies contributed data about UGHR and FGAR, including 1254 patients (622/1696 in the UGHR and 632/1571 in the FGAR, Table 2(A)). Random-effects model was applied because of significant heterogeneity (I2 = 55.80%, P = 0.003 Table 2(A)). Meta-analysis showed no significant difference between the two groups [RR = 0.963, 95% CI = (0.855,1.085), P = 0.536 > 0.05].

Outcomes

The primary outcome measures for enema reduction in cases of intussusception comprise resetting time, resetting pressure, success rate of reduction, duration of occult blood in stool, length of hospitalization, and recurrence.

Resetting time: Thirty-one studies contributed data about UGHR and FGAR, including 4236 patients (2146 in the UGHR and 2090 in the FGAR, Table 2(B)). Random-effects model was applied because of significant heterogeneity (I2 = 98.60%, P < 0.001 Table 2(B)). Meta-analysis showed significant difference between the two groups [WMD = -4.183, 95% CI = (-5.402, -2.964), P < 0.001; S2 Fig], which demonstrated significantly less resetting time of UGHR.

Resetting pressure: Four studies contributed data about UGHR and FGAR, including 594 patients (234 in the UGHR and 360 in the FGAR, Table 2(B)). Random-effects model was applied because of significant heterogeneity (I2 = 99.80%, P < 0.001 Table 2(B)). Meta-analysis showed significant difference between the two groups [WMD = 1.55, 95% CI = (-0.292,3.392), P = 0.099 > 0.05], which demonstrated significantly less resetting time of UGHR.

Success rate of reset: Forty-eight studies contributed data about UGHR and FGAR, including 8284 patients (4518/4722 in the UGHR and 3766/4305 in the FGAR, Table 2(A)). Random-effects model was applied because of significant heterogeneity (I2 = 71.40%, P < 0.001 Table 2(A)). Meta-analysis showed significant difference between the two groups [RR = 1.128, 95% CI = (1.099,1.157), P < 0.001; S3 Fig], which demonstrated significantly higher reset success rate of UGHR.

Duration of occult blood in stool: Seven studies contributed data about UGHR and FGAR, including 866 patients (435 in the UGHR and 431 in the FGAR, Table 2(B)). Random-effects model was applied because of significant heterogeneity (I2 = 89.70%, P < 0.001 Table 2(B)). Meta-analysis showed significant difference between the two groups [WMD = -0.808, 95% CI = (-1.098, -0.517), P < 0.001], which demonstrated significantly shorter duration of occult blood in stool of UGHR.

Length of hospitalization: Eighteen studies contributed data about UGHR and FGAR, including 3552 patients (1772 in the UGHR and 1780 in the FGAR, Table 2(B)). Random-effects model was applied because of significant heterogeneity (I2 = 99.40%, P < 0.001 Table 2(B)). Meta-analysis showed significant difference between the two groups [WMD = -1.215, 95% CI = (-1.58, -0.85), P < 0.001; S4 Fig], which demonstrated significantly shorter length of hospitalization of UGHR.

Recurrent rate: Twenty-five studies contributed data about UGHR and FGAR, including 479 patients (186/3134 in the UGHR and 293/2680 in the FGAR, Table 2(A)). Random-effects model was applied because of significant heterogeneity (I2 = 51.50%, P < 0.001 Table 2(A)). Meta-analysis showed significant difference between the two groups [RR = 0.391, 95% CI = (0.269,0.569), P = 0.002<0.05; S5 Fig], which demonstrated significantly less relapse rate of UGHR.

Complications

To describe the occurrence of complications during the enema reduction procedure for intussusception, we calculated the overall complication rate, perforation rate, as well as rates of vomiting and diarrhea.

Total complications rate: Twenty studies contributed data about UGHR and FGAR, including 253 patients (58/1349 in the UGHR and 195/1225 in the FGAR, Table 2(A)). Fixed-effects model was applied because of low heterogeneity (I2 = 13.30%, P = 0.288 Table 2(A)). Meta-analysis showed significant difference between the two groups [RR = 0.296, 95% CI = (0.225,0.389), P < 0.001; S6 Fig], which demonstrated significantly lower total complications rate of UGHR.

Perforation rate: Twenty-three studies contributed data about UGHR and FGAR, including 56 patients (13/ 2376 in the UGHR and 43/2381 in the FGAR, Table 2(A)). Fixed-effects model was applied because of low heterogeneity (I2 = 0.00%, P = 0.968 Table 2(A)). Meta-analysis showed significant difference between the two groups [RR = 0.405, 95% CI = (0.244,0.670), P < 0.001; S7 Fig], which demonstrated significantly lower perforation rate of UGHR.

Incidence of post-operative vomiting: Ten studies contributed data about UGHR and FGAR, including 46 patients (14/619 in the UGHR and 32/563 in the FGAR, Table 2(A)). Fixed-effects model was applied because of low heterogeneity (I2 = 0.00%, P = 0.825 Table 2(A)). Meta-analysis showed significant difference between the two groups [RR = 0.463 , 95% CI = (0.271,0.791), P < 0.001], which demonstrated significantly lower post-operative vomiting rate of UGHR.

Incidence of post-operative diarrhea: Nine studies contributed data about UGHR and FGAR, including 56 patients (13/ 558 in the UGHR and 43/507 in the FGAR, Table 2(A)). Fixed-effects model was applied because of low heterogeneity (I2 = 0.00%, P = 0.948 Table 2(A)). Meta-analysis showed significant difference between the two groups [RR = 0.318 , 95% CI = (0.182,0.558), P < 0.001], which demonstrated significantly lower post-operative diarrhea rate of UGHR.

Publication bias

Begg’s Test and Egger’s Test were performed, and Begg’s funnel plots were generated for some of the included records. Different subgroups were defined to assess publication bias (Table 3). Several largely symmetrical inverted funnel plots were observed (S8A–S8D Fig), and publications displaying significant bias were removed.

Discussions

Pediatric intussusception is characterized by the invagination of one segment of the bowel into an immediately adjacent segment, resulting in the obstruction of intestinal contents. Over time, compromised vascular flow to the affected segment can lead to ischemia, necrosis, and potentially perforation [10,66]. Therefore, early diagnosis and prompt treatment are imperative to improve prognosis. While radiological imaging plays a pivotal role in diagnosing and treating this condition, it is often not the initial choice in clinical practice due to concerns regarding radiation exposure. Ultrasound, conversely, stands out as the preferred imaging modality for diagnosis owing to its remarkable specificity (88%-100%), high sensitivity (98%-100%), and absence of ionizing radiation [67–69]. In cases of uncomplicated pediatric intussusception, imaging-guided enema reduction stands as the globally recognized standard for nonsurgical treatment [70]. To evaluate the efficacy and safety of ultrasound-guided hydrostatic enema reduction (UGHR) versus fluoroscopy-guided air enema reduction (FGAR), we conducted a comprehensive analysis encompassing clinical presentations, outcome parameters, and postoperative complications in both groups. Our primary objective is to equip healthcare practitioners with valuable insights for making informed treatment decisions when managing patients with intussusception.

We enrolled a total of 49 studies into our analysis, of which was based on a mixture of randomized and non-randomized trials. The outcomes of the meta-analysis concerning clinical presentations of intussusception, including paroxysmal crying and abdominal pain, the presence of an abdominal mass, time of onset and the occurrence of blood in stools, consistently indicated no significant differences when comparing the two groups.

The findings of this meta-analysis indicate that UGHR is characterized by a shorter resetting time, a higher success rate of reset, and a reduced duration of hospitalization (Table 2A and 2B). It has been proposed that during the UGHR procedure, real-time ultrasound enables the observation of the gradual movement of the intussusception towards the ileocecal region. During this phase, increasing the enema pressure can enhance the repositioning success rate and decrease the repositioning time. Additionally, the use of warm saline aids in the expulsion of intestinal contents, reducing the absorption of toxins by the intestinal tract. This, in turn, mitigates complications in children following the enema reduction, ultimately leading to a shorter hospital stay [12,36,41,62,71].

Complications arising from intussusception enema reduction are a critical aspect of assessing its safety, with intestinal perforation being one of the most severe complications [72]. During air enema, when the intestinal lumen pressure is high, the intestinal tube undergoes significant expansion. If excessive or sudden pressure is applied, air entering the terminal ileum may result in a tense pneumoperitoneum, potentially leading to intestinal perforation [73]. It has been reported [74] that UGHR may be less hygienic and could lead to intra-abdominal fecal contamination in case of intestinal perforation, which, if not promptly treated, can result in severe complications and endanger the patient’s life. The meta-analysis presented in this article demonstrates that UGHR repositioning is associated with a lower overall complication rate, including a lower incidence of perforation (Table 2A). Furthermore, the occurrence of postoperative vomiting and diarrhea is significantly reduced in children. Pan et al [36] suggest that this reduction in complications may be attributed to the slower movement of the water column during the water enema, causing less damage to the intestinal mucosa and possessing some mucosal dialysis function, resulting in a lower incidence of postoperative complications. Additionally, UGHR enables the measurement of intestinal tube hemodynamics, observation of the intestinal wall’s blood supply, and determination of its viability. This can effectively mitigate the risk of perforation due to high pressure during the enema procedure [41,63]. It is recommended to employ intermittent ultrasound monitoring to assess the intestinal canal diameter during enema operations, reducing the likelihood of perforation. UGHR also allows for clear visualization of the intussusception mass and early detection of pathological predisposing points or residual intussusception. Overall, it can be inferred that UGHR provides significant advantages in the treatment of intussusception in children.

However, the main disadvantage of UGHR is that the success of its enemas is significantly related to the experience of the operator, which requires pediatric surgeons to be taught and trained in ultrasound or radiology. This study exhibits several limitations too. Firstly, it’s worth noting that most studies included in this analysis were single-center trials. While our overall sample size is substantial, single-center studies may induce inevitable biases. Secondly, it’s noteworthy that the surgical team was also involved in authoring the reports. This potential author-surgeon bias should be taken into consideration when interpreting the findings. Thirdly, certain outcome measures, such as repositioning pressure, duration of postoperative blood in the stool, and postoperative vomiting or diarrhea, exhibited lower reliability due to a limited number of reported studies, resulting in a relatively small sample size for these specific parameters. Lastly, the enrolled studies were mostly from the Asia and Europe, an inevitable selection bias was existed.

Conclusions

In conclusion, it can be affirmed that both UGHR and FGAR represent safe and effective nonsurgical approaches for the management of pediatric acute intussusception. However, when comparing the two methods, UGHR emerges as the preferable choice. This preference is rooted in its nonradioactive nature, quicker repositioning times, higher success rates in repositioning, reduced postoperative hospitalization durations, fewer overall postoperative complications, and a notably decreased incidence of concurrent perforation when compared to FGAR.

Supporting information

S1 Checklist. PRISMA 2020 checklist.

(DOCX)

pone.0297985.s001.docx (33KB, docx)
S1 Fig

A. Risk of bias summary graph 1 for the included randomized controlled trial. B. Risk of bias summary graph 2 for the included randomized controlled trial.

(TIF)

pone.0297985.s002.tif (906.1KB, tif)
S2 Fig. Comparations of resetting time in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

(TIF)

pone.0297985.s003.tif (1.3MB, tif)
S3 Fig. Comparations of the rate of successful reset in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

(TIF)

pone.0297985.s004.tif (1.6MB, tif)
S4 Fig. Comparations of the length of hospitalization in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

(TIF)

pone.0297985.s005.tif (759.9KB, tif)
S5 Fig. Comparations of the rate of recurrent in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

(TIF)

pone.0297985.s006.tif (1.3MB, tif)
S6 Fig. Comparations of the rate of total complications in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

(TIF)

pone.0297985.s007.tif (925KB, tif)
S7 Fig. Comparations of the rate of perforation in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

(TIF)

pone.0297985.s008.tif (1.1MB, tif)
S8 Fig

A. Meta-analysis of male between UGHR and FGAR. B. Meta-analysis of the rate of perforation between UGHR and FGAR. C. Meta-analysis of vomiting between UGHR and FGAR. D. Meta-analysis of age between UGHR and FGAR.

(TIF)

pone.0297985.s009.tif (1MB, tif)
S1 Table. Newcastle-Ottawa scale scores for non-randomized controlled studies.

(DOCX)

pone.0297985.s010.docx (27KB, docx)
S1 Dataset. Minimal dataset underlying the results.

(XLSX)

pone.0297985.s011.xlsx (23.5KB, xlsx)

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

Foundation of Fujian High-level Clinical Medical Center(Siqi Xie, ETK2023016).

References

  • 1.Bruce J. Huh YS, Cooney DR, Karp MP, Allen JE,Jewett TJ. Intussusception: evolution of current management J Pediatr Gastroenterol Nutr. 1987. 6(5): p. 663–74. doi: 10.1097/00005176-198709000-00003 [DOI] [PubMed] [Google Scholar]
  • 2.Dias AR, Lopes RI, Do CR, Bonafe WW, Angelo LD Salvestro ML. Ileal duplication causing recurrent intussusception. J Surg Educ. 2007. 64(1): p. 51–3. doi: 10.1016/j.cursur.2006.09.003 [DOI] [PubMed] [Google Scholar]
  • 3.Bowker B. and Rascati S. Intussusception. JAAPA. 2018. 31(1): p. 48–49. doi: 10.1097/01.Jaa.0000527710.61686.02 [DOI] [PubMed] [Google Scholar]
  • 4.Savoie KB, Thomas F, Nouer SS, Langham MJ. Huang EY. Age at presentation and management of pediatric intussusception: A Pediatric Health Information System database study. Surgery.2017. 161(4): p. 995–1003. doi: 10.1016/j.surg.2016.09.030 [DOI] [PubMed] [Google Scholar]
  • 5.Jain S, Haydel MJ. Haydel, Child Intussusception. 2023. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 10. [PubMed] [Google Scholar]
  • 6.Lai AH, Phua KB, Teo EL, Jacobsen AS. Intussusception: a three-year review. Ann Acad Med Singap. 2002. 31(1): p. 81–5. 10.47102/annals-acadmedsg.V31N1p81. [DOI] [PubMed] [Google Scholar]
  • 7.Harrington L, Connolly B, Hu X, Wesson DE, Babyn P, Schuh S. Ultrasonographic and clinical predictors of intussusception. J Pediatr. 1998. 132(5): p. 836–9. doi: 10.1016/s0022-3476(98)70314-2 [DOI] [PubMed] [Google Scholar]
  • 8.RAVITCH M.M. Intussusception in infancy and childhood; an analysis of seventy-seven cases treated by barium enema. N Engl J Med. 1958. 259(22): p. 1058–64. doi: 10.1056/NEJM195811272592203 [DOI] [PubMed] [Google Scholar]
  • 9.Edwards EA, Pigg N, Courtier J, Zapala MA, Mackenzie JD, Phelps AS, Intussusception: past, present and future. Pediatr Radiol. 2017. 47(9): p. 1101–1108. doi: 10.1007/s00247-017-3878-x [DOI] [PubMed] [Google Scholar]
  • 10.Wu CW, Gao Y, Yang BS. iagnostic efficacy of transabdominal ultrasound combined with high frequency ultrasound in pediatric intussusception and its predictive value in the success or failure of warm saline enema reduction. Journal of Clinical Medicine Research and Practice. 2023. 8(20): p. 98–101. doi: 10.19347/j.cnki.2096-1413.202320025 [DOI] [Google Scholar]
  • 11.Kim YG, Choi BI, Yeon KM, Kim CW. Diagnosis and treatment of childhood intussusception using rea-time ultrasonography and saline enema: preliminary report. 1982. [Google Scholar]
  • 12.Yang H, Wang G, Ding Y, Li Y, Sun B, Yue M, Wang J, Song D. Effectiveness and safety of ultrasound-guided hydrostatic reduction for children with acute intussusception. Sci Prog. 2021. 104(3): p. 368504211040911. doi: 10.1177/00368504211040911 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Page MJ, Mckenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 2021. 372: p. n71. doi: 10.1136/bmj.n71 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med. 2015. 8(1): p. 2–10. doi: 10.1111/jebm.12141 [DOI] [PubMed] [Google Scholar]
  • 15.Stang A., Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010. 25(9): p. 603–5. doi: 10.1007/s10654-010-9491-z [DOI] [PubMed] [Google Scholar]
  • 16.Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res, 2018. 27(6): p. 1785–1805. doi: 10.1177/0962280216669183 [DOI] [PubMed] [Google Scholar]
  • 17.Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol, 2014. 14: p. 135. doi: 10.1186/1471-2288-14-135 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Wang DN, Tao Y, Zhang H,Yin XY. The value of high-frequency ultrasound imaging in pediatric intussusceptions diagnosis and enema reduction treatment. Journal of China Modern Doctor. 2013. 51(29): p. 82–83+86. CNKI:SUN:ZDYS.0.2013-29-034. [Google Scholar]
  • 19.Zhang PJ, Wang LY, Li Z. ltrasound guided hydrostatic enema in the treatment of pediatric intussusception. Journal of Dalian Medical Universit. 2014(4): p. 365–366,379. doi: 10.11724/jdmu.2014.04.14 [DOI] [Google Scholar]
  • 20.Guo QW, Wang LY. Comparison of ultrasound-supervised water pressure enema and X-ray air enema in pediatric intussusception. Chinese Journal of Radiation Health. 2014. 23(03): p. 269+272. doi: 10.13491/j.cnki.issn.1004-714x.2014.03.034 [DOI] [Google Scholar]
  • 21.Yi WT, He ZN. Analysis of the effect of ultrasound monitoring of water pressure enema in the treatment of pediatric intussusception. Journal of Practical Integrative Medicine. 2015. 15(11): p. 47–48. doi: 10.13638/j.issn.1671-4040.2015.11.028 [DOI] [Google Scholar]
  • 22.Zhong ZL, Guo GC, Zhang SH. Aplication of high -frequency ultrasound value in the diagnosis and treatment of children with acute intussusception. CHINA MEDICAL HERALD. 2015. 12(19): p. 114–117. doi: 10.3969/j.issn.1002-0101.2012.11.031 [DOI] [Google Scholar]
  • 23.Wu M. Analysis of the effect of warm saline enema restoration under real-time ultrasound-guided surveillance in the treatment of pediatric primary intussusception. Chinese Journal of Practical Medicine. 2015. 10(11): p. 124–125. doi: 10.14163/j.cnki.11-5547/r.2015.11.083 [DOI] [Google Scholar]
  • 24.Li XY. The Value of High Frequency Ultrasound Imaging in Diagnosis of Pediatric Intussusception and Enema Therapy. China Continuing Medical Education. 2015(19): p. 45–46. doi: 10.3969/j.issn.1674-9308.2015.19.033 [DOI] [Google Scholar]
  • 25.Jiang WJ, Ma JM, Li ZX, Cao LM. Curative effect observation of different water pressure under ultrasound-guided enema for children with intussusception. Journal of Practical Hospital Clinics. 2016. 13(06): p. 60–62. doi: 10.3969/j.issn.1672-6170.2016.06.021 [DOI] [Google Scholar]
  • 26.Liao YY. Effect analysis on hydrostatic reduction of intussusception monitored by color Doppler ultrasound. Journal of China Modern Doctor. 2016. 54(15): p. 90–92. CNKI:SUN:ZDYS.0.2016-15-027. [Google Scholar]
  • 27.Yang CY, Lian H, Jin RT. The comparative analysis of different ways in the treatment of pediatric intussusception. Journal of China Modern Doctor. 2016. 54(09): p. 90–92. [Google Scholar]
  • 28.Deng ME, Yang YG, Chen YZ, Huang Z, Zou YJ, Ye WW, et al. Hydrostatic enema under ultrasound guidance for reduction of intussusception in children. Journal of Wannan Medical College. 2016. 35(01): p. 86–89. doi: 10.3969/j.issn.1002-0217.2016.01.026 [DOI] [Google Scholar]
  • 29.He T, Yang YH, Zhang ZZ. Ultrasound VS X-ray for disease diagnosis and guiding enema treatment in infantile intussusception. World Chinese Digestive Journal. 2017. 25(02): p. 199–203. doi: 10.11569/wcjd.v25.i2.199 [DOI] [Google Scholar]
  • 30.Xu O. Analysis of the efficacy of three methods of treating pediatric intussusception. Journal of Clinical Medical. 2017. 4(34): p. 6598–6599. doi: 10.16281/j.cnki.jocml.2017.34.043 [DOI] [Google Scholar]
  • 31.Zhang CQ, Wang Y. Comparative study of ultrasound-guided water pressure enema and X-ray air enema in the treatment of pediatric intussusception. Journal of Modern Medical Imaging. 2017. 26(02): p. 500–501. doi: 10.3969/j.issn.1006-7035.2017.02.115 [DOI] [Google Scholar]
  • 32.Xie X, Wu Y, Wang Q, Zhao Y, Chen G, Xiang B. A randomized trial of pneumatic reduction versus hydrostatic reduction for intussusception in pediatric patients %J J Pediatr Surg. 2018. 53(8): p. 1464–1468. doi: 10.1016/j.jpedsurg.2017.08.005 [DOI] [PubMed] [Google Scholar]
  • 33.Wang ZY, Xiao D, Mao JX. Comparative analysis of the clinical efficacy of fluoroscopic air enema and ultrasound-guided water pressure enema in the treatment of pediatric intussusception. Heilongjiang Journal of Traditional Chinese Medicine. 2018. 47(05): p. 46–47. CNKI:SUN:HLZY.0.2018-05-024. [Google Scholar]
  • 34.Yu XW, Men DW. Exploration of the therapeutic effect of ultrasound-guided water pressure enema on pediatric intussusception. World Abstracts of Medical Information. 2018. 18(81): p. 157. doi: 10.19613/j.cnki.1671-3141.2018.81.119 [DOI] [Google Scholar]
  • 35.Wu YY, Chen Q, Li ZX, Cai ZQ, Zhou Q, Ju XM, et al. Clinical value of ultrasound-guided normal saline enema reduction in treatment of children with intussusception. Journal of Southwest Medical Universit. 2018. 41(04): p. 317–321. doi: 10.3969/j.issn.2096-3351.2018.04.006 [DOI] [Google Scholar]
  • 36.Pan ZB, Gao Q, Huang H, Lu XY. Effect comparison between hydrostatic reduction under B-ultrasound and air perfusion under X-ray treating cllildren intussusception. China Medicine Herald. 2018. 15(08): p. 116–119. CNKI:SUN:YYCY.0.2018-08-029 [Google Scholar]
  • 37.Deng JG, Chen ZQ, Li DP. Comparison of the effects of hydrostatic enemae monitored by ultrasound and air enemae under X-ray on intussusception in Children. Journal of Baotou Medical College. 2018. 34(01): p. 33–34+82. doi: 10.16833/j.cnki.jbmc.2018.01.014 [DOI] [Google Scholar]
  • 38.Zhang SG, Wu XJ.Observation on the application effect of air enema under ultrasound to rectify intussusception in pediatrics. Frontiers of Medicine. 2018. 8(10): p. 94. doi: 10.3969/j.issn.2095-1752.2018.10.071 [DOI] [Google Scholar]
  • 39.Zhou ZB, Yao ZB. Clinical application of real-time ultrasound-guided warm saline enema in the treatment of pediatric intussusception. Journal of Imaging Research and Medical Applications. 2019. 3(13): p. 157–158. CNKI:SUN:YXYY.0.2019-13-102. [Google Scholar]
  • 40.Zhao YL, Zhang Y. The Application Value of High-frequency Ultrasound in the Diagnosis of Infantile Acute Intussusception and in the Hydropressure Enema Reduction Treatment. Chinese Journal of Coloproctol. 2019. 39(08): p. 44–45. doi: 10.3969/j.issn.1000-1174.2019.08.022 [DOI] [Google Scholar]
  • 41.Wang DL, Kang Q, Wang HM, Dai XK, Zhang MM. Efficacy and Safety of New Ultrasound-guided Hydrostatic Reduction vs Conventional Pneumatic Reduction for Intussusception in Pediatric Patients. Chinese Journal of General Practice. 2019. 22(06): p. 712–714. doi: 10.12114/j.issn.1007-9572.2018.00.264 [DOI] [Google Scholar]
  • 42.Jiang JZ, Qin DR, Hu J. Comparison of B‐ultrasonic Hydrostatic Enema and X‐ray Air Enema in Treatment of Children Acute Intussusception. Journal of Clinical Research in Medicine. 2019. 36(9): p. 1730–1732. doi: 10.3969/j.issn.1671‐7171.2019.09.022. [DOI] [Google Scholar]
  • 43.Wang L. Clinical significance of color Doppler ultrasound in the diagnosis of pediatric intussusception and ultrasound-monitored saline enema repositioning.Healthmust-Readmagazine. 2019(11): p. 273–274. [Google Scholar]
  • 44.Zhang LW. Clinical effect analysis of air enema under X-ray and water pressure enema under ultrasound surveillance in the treatment of pediatric intussusception. Henan Journal of Surgery. 2020. 26(03): p. 105–106. doi: 10.16193/j.cnki.hnwk.2020.03.053 [DOI] [Google Scholar]
  • 45.Guo XM. Study on the Clinical Value of Pediatric Intussusception Treated with Ultrasound-guided Combined Enema Repositioning Therapy. Contemporary Medicine. 2020. 26(31): p. 165–166. doi: 10.3969/j.issn.1009-4393.2020.31.071 [DOI] [Google Scholar]
  • 46.Wang K, Li YP, Zhu YL. Comparison of Therapeutic Effect of Ultrasound Guided Hydrostatic Enema and Air Enema Treatment Under X − ray Guide on Children Intussusception. Henan Journal of Medical Research. 2020. 29(25): p. 4629–4632. doi: 10.3969/j.issn.1004-437X.2020.25.007 [DOI] [Google Scholar]
  • 47.Li XL. Comparison of the effects of different modalities of enemas in the treatment of pediatric intussusception. Chinese Journal of Practical Medicine. 2020. 15(19): p. 58–60. doi: 10.14163/j.cnki.11-5547/r.2020.19.023 [DOI] [Google Scholar]
  • 48.Qi YB.Effectiveness of water pressure enema under color ultrasound surveillance in the treatment of pediatric intussusception. Journal of Medical Aesthetics and Cosmetology. 2020. 29(1): p. 46. [Google Scholar]
  • 49.Sui BZ. Clinical Analysis of Different Standard WAter Pressure Enema under Ultrasound Guidance for PediatriC Intussusception. China Standardization Journal. 2021(22): p. 232–234. doi: 10.3969/j.issn.1002-5944.2021.22.056 [DOI] [Google Scholar]
  • 50.Cai XY. Observation on the therapeutic effect of ultrasound-guided saline enema for intussusception in pediatrics. Journal of Modern Medical Imagin. 2021. 30(03): p. 573–575. doi: 10.3969/j.issn.1006-7035.2021.03.053 [DOI] [Google Scholar]
  • 51.Ding BP, Lai YY. Effect of ultrasound-under-hydropressure enema repositioning on the success rate of repositioning and the positive rate of serum CRP in children with intussusception. Primary Care Forum. 2021. 25(05): p. 736–738. doi: 10.19435/j.1672-1721.2021.05.079 [DOI] [Google Scholar]
  • 52.Zhang L, Yang J, Yu SW, Sun K, Xiang YC, Wei YQ, et al. The stress response of water pressure enema under the guidance of ultrasound for children with acute intussusceptions and its effect on gastrointestinal hormone. Journal of Practical Hospital Clinic. 2021. 18(1): p. 27–30. doi: 10.3969/j.issn.1672-6170.2021.01.008 [DOI] [Google Scholar]
  • 53.Chen ZQ, Deng JG, Chen ZJ, Luo MS, Wu QH. Effect of normal saline enema reduction combined with B-ultrasound monitoring in the treatment of acute intussusception in children. Chinese community Doctots. 2021. 37(14): p. 25–26. doi: 10.3969/j.issn.1007-614x.2021.14.011 [DOI] [Google Scholar]
  • 54.Lian TF, Du YY, Fan L. Comparison of the effects and complications of air and water pressure enemas in the treatment of pediatric acute intussusception. Primary Care Forum. 2021. 25(1): p. 39–41. doi: 10.19435/j.1672-1721.2021.01.017 [DOI] [Google Scholar]
  • 55.Chen ZQ, Deng JG, Chen ZJ, Luo MS, Wu QH. Study on clinical effect of warm normal saline enema reduction under the guidance of B-ultrasound in children with intussusception. Chinese Journal of Modern Drug Application. 2021. 15(9): p. 34–37. doi: 10.14164/j.cnki.cn11-5581/r.2021.09.011 [DOI] [Google Scholar]
  • 56.Du T, Chang YL. Efficacy of saline enema under ultrasound monitoring in children with acute intussusception. Henan Medical Research Journal. 2021. 30(5): p. 826–828. doi: 10.3969/j.issn.1004-437X.2021.05.018 [DOI] [Google Scholar]
  • 57.Pei XY. Clinical value of ultrasound-guided treatment of pediatric intussusception using saline enema repositioning. Journal of Health Care Guid. 2021(7): p. 251. [Google Scholar]
  • 58.Liu ST, Tang XB, Li H, Chen D, Lei J, Bai YZ. Ultrasound-guided hydrostatic reduction versus fluoroscopy-guided air reduction for pediatric intussusception: a multi-center, prospective, cohort study %J World J Emerg Surg. 2021. 16(1): p. 3. doi: 10.1186/s13017-020-00346-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Han T, Chang QY. Analysis about the effects and complications of wam saline enema under ultrasound moIlitoring in the treatment of intussusception. Xinjiang Medical Journal. 2022. 52(11): p. 1320–1323. [Google Scholar]
  • 60.Liu H, Zhou B, Xu SS, Dai HW, Yuan X, Huang DQ. Research on Clinical Value of Warm Normal Saline Enema Reduction Guide by Real-time Color Doppler Ultrasound in the Treatment of Pediatric Intussusception. Medical Innovation of China. 2022. 19(04): p. 35–38. doi: 10.3969/j.issn.1674-4985.2022.04.008 [DOI] [Google Scholar]
  • 61.Lv YX, Qiang Q, Wang WB. Aplication of Ultrasound-guided Hydraulic Enema in the Diagnosis and Treatment of Acute Intussusception. Imaging Science and Photochemistry. 2022. 40(01): p. 147–150. doi: 10.7517/issn.1674-0475.210725 [DOI] [Google Scholar]
  • 62.Liu XF, Li DL. Clinical application of warm normal saline enema reduction under real-time ultrasound guidance and monitoring in children with primary intussusception. Journal of Marriage, Parenthood and Health. 2022. 28(10): p. 5–6. [Google Scholar]
  • 63.Pu YB. Clinical Comparisons of Hydrostatic Enema and Air Enema on Treatment of Indigitation. Journal of Aerospace Medicine. 2022. 33(12): p. 1416–1418. doi: 10.3969/j.issn.2095-1434.2022.12.004 [DOI] [Google Scholar]
  • 64.Chukwu IS, Ekenze SO, Ezomike UO, Chukwubuike KE, Ekpemo SC. Ultrasound-guided reduction of intussusception in infants in a developing world: saline hydrostatic or pneumatic technique? % J Eur J Pediatr. 2023. 182(3): p. 1049–1056. doi: 10.1007/s00431-022-04765-5 [DOI] [PubMed] [Google Scholar]
  • 65.Lian DD, Sun C, Zhang CP, Sun ZH, Song GX. Comparison of ultrasound-guided saline enema and X-ray fluoroscopic air enema in pediatric intussusception repositioning. Chinese Journal of Modern General Surgery. 2023. 26(01): p. 56–58. doi: 10.3969/j.issn.1009-9905.2023.01.014 [DOI] [Google Scholar]
  • 66.Marsicovetere P, Ivatury ST, White B, Holubar SD. Intestinal Intussusception: Etiology, Diagnosis, and Treatment. Clin Colon Rectal Surg. 2017. 30(1): p. 30–39. doi: 10.1055/s-0036-1593429 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Verschelden P, Filiatrault D, Garel L, Grinon A, Perreault G, Boisvert J, et al. Intussusception in children: reliability of US in diagnosis—a prospective study. Radiology. 1992. 184(3): p. 741–4. doi: 10.1148/radiology.184.3.1509059 [DOI] [PubMed] [Google Scholar]
  • 68.Daneman A, Alton DJ. Intussusception. Issues and controversies related to diagnosis and reduction. Radiol Clin North Am. 1996. 34(4): p. 743–56. 10.1016/S0033-8389(22)00506-1. [DOI] [PubMed] [Google Scholar]
  • 69.Plut D, Phillips GS, Johnston PR, Lee EY. Practical Imaging Strategies for Intussusception in Children. AJR Am J Roentgenol. 2020. 215(6): p. 1449–1463. doi: 10.2214/AJR.19.22445 [DOI] [PubMed] [Google Scholar]
  • 70.Schmit P, Rohrschneider WK, Christmann D. Intestinal intussusception survey about diagnostic and nonsurgical therapeutic procedures. Pediatr Radiol. 1999. 29(10): p. 752–61. doi: 10.1007/s002470050689 [DOI] [PubMed] [Google Scholar]
  • 71.Lim R, Lee T, Ng J, Quek KF, Abdul WN, Amansah SL, et al. Factors associated with ultrasound-guided water enema reduction for pediatric intussusception in resource-limited setting: potential predictive role of thrombocytosis and anemia. J Pediatr Surg. 2018. 53(11): p. 2312–2317. doi: 10.1016/j.jpedsurg.2018.01.004 [DOI] [PubMed] [Google Scholar]
  • 72.Demir M, Akin M, Unal A, Kaba M, Sever N, Dokucu AI. Our treatment approaches in recurrent chronic intussusceptions. Ulus Travma Acil Cerrahi Derg. 2022. 28(9): p. 1317–1322. doi: 10.14744/tjtes.2022.56954 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Fallon SC, Kim ES, Naik-Mathuria BJ, Nuchtern JG, Cassady CI, Rodriguez JR. Needle decompression to avoid tension pneumoperitoneum and hemodynamic compromise after pneumatic reduction of pediatric intussusception. Pediatr Radiol. 2013. 43(6): p. 662–7. doi: 10.1007/s00247-012-2604-y [DOI] [PubMed] [Google Scholar]
  • 74.Chew R, Ditchfield M, Paul E, Goergen SK. Comparison of safety and efficacy of image-guided enema reduction techniques for paediatric intussusception: A review of the literature.J Med Imaging Radiat Oncol. 2017. 61(6): p. 711–717. doi: 10.1111/1754-9485.12601 [DOI] [PubMed] [Google Scholar]

Decision Letter 0

Ozlem Boybeyi-Turer

8 Dec 2023

PONE-D-23-36429Air enema reduction versus hydrostatic enema reduction for intussusceptions in children: An updated systematic review and meta-analysisPLOS ONE

Dear Dr. Xie,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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ACADEMIC EDITOR:

This systematic review and meta-analysis presents the systematic review results of the management of pediatric intussusception with ultrasound-guided hydrostatic reduction vs fluoroscopic-guided air reduction. The study protocol was registered and follows PRISMA guidelines. Overall it is a well-written manuscript and that comparison of two management approach is worthwhile. However, the manuscript need revision regarding following besides the ones addressed by the reviewers:

  • The methodology needs to be revised. The details of search strategy, definition of PICOS, the inclusion and exclusion criteria should be addressed more clearly for the readers. In addition, the selection process and data extraction process should be given clearly.

  • Regarding screening process, the reason for exclusion of the studies should be given clearly in order to prevent bias while interpreting the results.

  • When interpreting the results, it will be better to comment on the distribution of the countries in which the included studies were published.

  • Regarding the funding, the authors stated that there is no funding during submission, they stated that there is funding in the end of the article. Please verify clearly.  

==============================

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Ozlem Boybeyi-Turer

Academic Editor

PLOS ONE

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Additional Editor Comments:

This systematic review and meta-analysis presents the systematic review results of the management of pediatric intussusception with ultrasound-guided hydrostatic reduction vs fluoroscopic-guided air reduction. The study protocol was registered and follows PRISMA guidelines. Overall it is a well-written manuscript and that comparison of two management approach is worthwhile. However, the manuscript need revision regarding following besides the ones addressed by the reviewers:

• The methodology needs to be revised. The details of search strategy, definition of PICOS, the inclusion and exclusion criteria should be addressed more clearly for the readers. In addition, the selection process and data extraction process should be given clearly.

• Regarding screening process, the reason for exclusion of the studies should be given clearly in order to prevent bias while interpreting the results.

• When interpreting the results, it will be better to comment on the distribution of the countries in which the included studies were published.

• Regarding the funding, the authors stated that there is no funding during submission, they stated that there is funding in the end of the article. Please verify clearly.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Reviewer Comments

RE: PONE-D-23-36429

The authors of this manuscript gave a detailed systematic review and meta-analysis of studies done over a period of 20 years (2003 – 2023) on non-operative management of intussusception. The objective was to compare the efficacy and outcome of fluoroscopy-guided air enema

reduction (FGAR) and ultrasound-guided hydrostatic enema reduction (UGHR) modalities in the treatment of intussusception in children. The manuscript is well written, and the language used is easy to comprehend. To improve on the quality of the manuscript, I suggest the following revisions.

Title: The title is better as “Air enema reduction versus hydrostatic enema reduction for intussusceptions in children: A systematic review and meta-analysis”. Avoid such terms as updated or comprehensive. Meta-analysis is expected to be comprehensive and to provide updated information

Introduction: There is need for more details on rationale for the study, a study question, and a hypothesis

Methods: Was any article excluded based on the language of publication? How many authors independently reviewed the article from the initial search, and critical review of included articles? How did the authors address inter-rater variability in the review of included articles?

Discussion: Repeat of information already in the methods and results sections. I would like a succinct summary of your main findings.

References: The referencing style is not uniform

Reviewer #2: This systematic review and meta-analysis address the management of pediatric intussusception with ultrasound-guided hydrostatic reduction (UGHR) vs fluoroscopic-guided air reduction (FGAR). The trial was registered and follows PRISMA guidelines. Authors assessed included articles for bias and focused on high quality studies although the bulk of included studies are non-randomized cohorts. The main claim of the paper is the superiority of UGHR. Given the frequency of intussusception in pediatrics, it is helpful to compare the two methods of reduction although most institutions have limitations in training and/or availability of reduction 24/7 that dictates the institutional preferred method. The main concern with regards to the methodology of this paper is the initial screening and selection of articles. Authors note 1231 articles were identified through a comprehensive literature search but “prior to screening, 986 records expunged from consideration”. Unless it is made clear how and why these papers were expunged prior to screening, this review and meta-analysis is incomplete and results may be inaccurate due to an exclusion of the bulk of the literature identified without screening for relevance so I would invite the authors to screen all relevant literature in the next revision.

The authors review the two methods of reduction in the introduction and discussion. As noted above, the included literature in the search seems to be a sub-selection without appropriate screening of all literature identified by the initial search. I would request clarification regarding the 986 articles that were identified but expunged prior to screening. I would suggest the authors screen these 986 articles using their inclusion and exclusion criteria to ensure all relevant literature is considered.

It is helpful that the authors have assessed the risk of bias for individual studies. I would consider highlighting in the discussion that the literature is based on a mix of randomized and non-randomized trials. Specifically, the fact that one very large retrospective cohort study contributes 1119 patients to the total of 9391 (and most of the included randomized trials are much smaller than the non-randomized). Although this information is available in Table 1, I would suggest making it more accessible to readers.

Overall this is a well-written manuscript and the comparison of UGHR and FGAR is worthwhile; however, revision is required to include screening of all appropriate literature as there may be selection bias with the current methods that do not explain why only a subset of literature underwent screening.

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2024 Mar 18;19(3):e0297985. doi: 10.1371/journal.pone.0297985.r002

Author response to Decision Letter 0

2 Jan 2024

# ACADEMIC EDITOR

Q 1: The methodology needs to be revised. The details of search strategy, definition of PICOS, the inclusion and exclusion criteria should be addressed more clearly for the readers. In addition, the selection process and data extraction process should be given clearly.

A 1: Thank you very much for your valuable suggestions, I will answer your questions in detail gladly.

Detailed part of the search strategy: we formulated the search strategy, inclusion criteria and exclusion criteria according to the PICOS principles: (1) Type of study: randomized or non-randomized controlled trial, with the language limited to Chinese and English; (2) Participants of the study: pediatric patients (aged <18 years) who underwent enemas due to intussusception; (3) Interventions adopted: fluoroscopic air enema or ultrasound-guided saline enemas were used; (4) The main outcome indicators: time to reset, success rate of reset, recurrence rate, and occurrence of postoperative complications. (5) Search strategy: Take Pubmed as an example: a specific search strategy is shown (see the suppl-figure 1 and revised-Figure 1 in the manuscript), and we have revised the text in red (page 5, line 2-9).

Literature search and data collection part: The literature retrieval and data collection are to be carried out by at least two researchers. They will independently read the titles and abstracts of the literature, excluding those that are not relevant to the content of this study. Subsequently, they will carefully read the full texts according to inclusion and exclusion criteria, extracting relevant information. In case of disagreements, resolution will be sought through negotiation, or a third researcher may be consulted for assistance in making a judgment. (page 6, line 21-22, page 7, line 1-6)

Q 2: Regarding screening process, the reason for exclusion of the studies should be given clearly in order to prevent bias while interpreting the results.

A 2: I am so grateful for the valuable advice, the literature screening process involved 2 researchers independently reading the titles and abstracts of the literature to initially exclude literature that did not match the content of this study for the specific reasons for exclusion shown in revised-Figure 1 in the manuscript

Q 3: When interpreting the results, it will be better to comment on the distribution of the countries in which the included studies were published.

A 3: Thank you for this valuable suggestion. We have added associated information in the result and the limitations.

Q 4: Regarding the funding, the authors stated that there is no funding during submission, they stated that there is funding in the end of the article. Please verify clearly.

A 4: I am very sorry for your misunderstanding due to my negligence during submission, this article does have financial support and we will make changes subsequently.

# Reviewer 1

Q 1: Title: The title is better as “Air enema reduction versus hydrostatic enema reduction for intussusceptions in children: A systematic review and meta-analysis”. Avoid such terms as updated or comprehensive. Meta-analysis is expected to be comprehensive and to provide updated information

A1: Thank you very much for your valuable suggestions, the title of this article has been changed. (see the title)

Q 2: Introduction: There is need for more details on rationale for the study, a study question, and a hypothesis.

A2: Thank you very much for your valuable suggestions, we have revised the article's introduction. (see the introduction in red）

Q 3: Methods: Was any article excluded based on the language of publication? How many authors independently reviewed the article from the initial search, and critical review of included articles? How did the authors address inter-rater variability in the review of included articles?

A 3: I am so grateful for the valuable advice. We formulated the search strategy, inclusion criteria and exclusion criteria according to the PICOS principles: (1) Type of study: randomized or non-randomized controlled trial, with the language limited to Chinese and English; (2) Participants of the study: pediatric patients (aged <18 years) who underwent enemas due to intussusception; (3) Interventions adopted: fluoroscopic air enema or ultrasound-guided saline enemas were used; (4) The main outcome indicators: time to reset, success rate of reset, recurrence rate, and occurrence of postoperative complications. (page 5, line 2-9)

The literature retrieval and data collection are to be carried out by at least two researchers. They will independently read the titles and abstracts of the literature, excluding those that are not relevant to the content of this study. Subsequently, they will carefully read the full texts according to inclusion and exclusion criteria, extracting relevant information. In case of disagreements, resolution will be sought through negotiation, or a third researcher may be consulted for assistance in making a judgment. (page 6, line 21-22, page 7, line 1-6)

Q 4: Discussion: Repeat of information already in the methods and results sections. I would like a succinct summary of your main findings.

A4: Thank you very much for your valuable suggestions, in the discussion section of the article, we focus on statistically significant indicators and discuss the reasons for such results in the context of the clinic, so it is not concise enough, and We have also made certain modifications. (see the discussion in red)

Q 5: References: The referencing style is not uniform.

A4: Please accept my sincere thanks for your help with my article regarding the revision of the references, which I have accepted and revised. (see the references)

# Reviewer 2

Q 1: The authors review the two methods of reduction in the introduction and discussion. As noted above, the included literature in the search seems to be a sub-selection without appropriate screening of all literature identified by the initial search. I would request clarification regarding the 986 articles that were identified but expunged prior to screening. I would suggest the authors screen these 986 articles using their inclusion and exclusion criteria to ensure all relevant literature is considered.

A1: Please accept my sincere thanks for your help with my article, we developed inclusion and exclusion criteria based on the PICOS principles and conducted a comprehensive literature search in which two investigators independently read article titles and abstracts to initially exclude literature that did not match the content of this study, with specific reasons for exclusion demonstrated (see the suppl-figure 1 and revised-Figure 1 in the manuscript), and we have revised the text in red (page 5, line 2-9).

Q 2: It is helpful that the authors have assessed the risk of bias for individual studies. I would consider highlighting in the discussion that the literature is based on a mix of randomized and non-randomized trials. Specifically, the fact that one very large retrospective cohort study contributes 1119 patients to the total of 9391 (and most of the included randomized trials are much smaller than the non-randomized). Although this information is available in Table 1, I would suggest making it more accessible to readers.

A2: I am so grateful for the valuable advice, we have made changes in the discussion section and added that element. (page 15, line 14-15)

Q 3: Overall this is a well-written manuscript and the comparison of UGHR and FGAR is worthwhile; however, revision is required to include screening of all appropriate literature as there may be selection bias with the current methods that do not explain why only a subset of literature underwent screening.

A 3: Thank you very much for your valuable suggestions, As described in the text, our literature search strategy was to abstract or title all literature including "intussusception", "enema", "ultrasound-guided", so by reading the title and abstract of those articles, it was possible to exclude most of the literature. For example, studies in which the subject was not a child, uncontrolled studies (only UGHR or FGAR), or fluoroscopic or ultrasound-guided enemas with other fluid will be excluded after screening. (see the suppl-figure 1 and revised-Figure 1 in the manuscript)

Attachment

Submitted filename: Response to Reviewers.docx

pone.0297985.s012.docx (24.3KB, docx)

Decision Letter 1

Ozlem Boybeyi-Turer

16 Jan 2024

Air enema reduction versus hydrostatic enema reduction for intussusceptions in children: An systematic review and meta-analysis

PONE-D-23-36429R1

Dear Dr. Xie,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Ozlem Boybeyi-Turer

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Ozlem Boybeyi-Turer

8 Mar 2024

PONE-D-23-36429R1

PLOS ONE

Dear Dr. Xie,

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on behalf of

Professor Ozlem Boybeyi-Turer

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Checklist. PRISMA 2020 checklist.

    (DOCX)

    pone.0297985.s001.docx (33KB, docx)
    S1 Fig

    A. Risk of bias summary graph 1 for the included randomized controlled trial. B. Risk of bias summary graph 2 for the included randomized controlled trial.

    (TIF)

    pone.0297985.s002.tif (906.1KB, tif)
    S2 Fig. Comparations of resetting time in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

    (TIF)

    pone.0297985.s003.tif (1.3MB, tif)
    S3 Fig. Comparations of the rate of successful reset in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

    (TIF)

    pone.0297985.s004.tif (1.6MB, tif)
    S4 Fig. Comparations of the length of hospitalization in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

    (TIF)

    pone.0297985.s005.tif (759.9KB, tif)
    S5 Fig. Comparations of the rate of recurrent in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

    (TIF)

    pone.0297985.s006.tif (1.3MB, tif)
    S6 Fig. Comparations of the rate of total complications in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

    (TIF)

    pone.0297985.s007.tif (925KB, tif)
    S7 Fig. Comparations of the rate of perforation in ultrasound-guided hydrostatic enema reduction (UGHR) and fluoroscopy-guided air enema reduction (FGAR).

    (TIF)

    pone.0297985.s008.tif (1.1MB, tif)
    S8 Fig

    A. Meta-analysis of male between UGHR and FGAR. B. Meta-analysis of the rate of perforation between UGHR and FGAR. C. Meta-analysis of vomiting between UGHR and FGAR. D. Meta-analysis of age between UGHR and FGAR.

    (TIF)

    pone.0297985.s009.tif (1MB, tif)
    S1 Table. Newcastle-Ottawa scale scores for non-randomized controlled studies.

    (DOCX)

    pone.0297985.s010.docx (27KB, docx)
    S1 Dataset. Minimal dataset underlying the results.

    (XLSX)

    pone.0297985.s011.xlsx (23.5KB, xlsx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    pone.0297985.s012.docx (24.3KB, docx)

    Data Availability Statement

    All relevant data are within the manuscript and its Supporting Information files.

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