Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants.

The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides a first layer of immunological defense within the abdomen. Here, we investigated the mechanisms that mediate the capture of peritoneal contaminants during peritonitis. Single-cell RNA sequencing and spatial analysis of omental stromal cells revealed that the surface of FALCs were covered by CXCL1+ mesothelial cells, which we termed FALC cover cells. Blockade of CXCL1 inhibited the recruitment and aggregation of neutrophils at FALCs during zymosan-induced peritonitis. Inhibition of protein arginine deiminase 4, an enzyme important for the release of neutrophil extracellular traps, abolished neutrophil aggregation and the capture of peritoneal contaminants by omental FALCs. Analysis of omental samples from patients with acute appendicitis confirmed neutrophil recruitment and bacterial capture at FALCs. Thus, specialized omental mesothelial cells coordinate the recruitment and aggregation of neutrophils to capture peritoneal contaminants.

Short Postoperative Intravenous Versus Oral Antibacterial Therapy in Complicated Acute Appendicitis: A Pilot Noninferiority Randomized Trial.

OBJECTIVE: The purpose of this study is to investigate noninferiority of postoperative oral administration of antibiotics in complicated appendicitis. BACKGROUND: Recent investigations have used exclusively intravenous administration of antibiotics when comparing outcomes of postoperative antibacterial therapy in complicated appendicitis. We hypothesized that oral antibacterial treatment results in noninferior outcomes in terms of postoperative infectious complications as intravenous treatment. METHODS: In this pilot, open-label, prospective randomized trial, all consecutive adult patients with complicated appendicitis, including gangrenous appendicitis, perforated appendicitis, and appendicitis with periappendicular abscess between November 2020 and January 2023, were randomly allocated to 24-hour intravenous administration of antibiotics versus 24-hour oral administration of antibiotics after appendectomy. Primary outcomes included 30-day postoperative complications per Comprehensive Complication Index. The secondary outcome was hospital length of stay. Follow-up analysis at 30 days was conducted per intention to treat and per protocol. The study was registered at ClinicalTrials.gov (NCT04947748). RESULTS: A total of 104 patients were enrolled, with 51 and 53 cases allocated to the 24-hour intravenous and the 24-hour oral treatment group, respectively. Demographic profile and disease severity score for acute appendicitis were similar between the study groups. There were no significant differences between the study groups in terms of 30-day postoperative complications. Median Comprehensive Complication Index did not differ between the study groups. Hospital length of stay was similar in both groups. CONCLUSIONS: In the current pilot randomized controlled trial, the 24-hour oral antibiotic administration resulted in noninferior outcomes when compared with the 24-hour intravenous administration of antibiotics after laparoscopic appendectomy in complicated appendicitis.

The Use and Impact of a Decision Support Tool for Appendicitis Treatment.

OBJECTIVE: Since introducing new and alternative treatment options may increase decisional conflict, we aimed to describe the use of the decision support tool (DST) and its impact on treatment preference and decisional conflict. BACKGROUND: For the treatment of appendicitis, antibiotics are an effective alternative to appendectomy, with both approaches associated with a different set of risks (eg, recurrence vs surgical complications) and benefits (eg, more rapid return to work vs decreased chance of readmission). Patients often have limited knowledge of these treatment options, and DSTs that include video-based educational materials and questions to elicit patient preferences about outcomes may be helpful. Concurrent with the Comparing Outcomes of Drugs and Appendectomy trials, our group developed a DST for appendicitis treatment ( www.appyornot.org ). METHODS: A retrospective cohort including people who self-reported current appendicitis and used the AppyOrNot DST between 2021 and 2023. Treatment preferences before and after the use of the DST, demographic information, and Ottawa Decisional Conflict Scale (DCS) were reported after completing the DST. RESULTS: A total of 8243 people from 66 countries and all 50 U.S. states accessed the DST. Before the DST, 14% had a strong preference for antibiotics and 31% for appendectomy, with 55% undecided. After using the DST, the proportion in the undecided category decreased to 49% ( P < 0.0001). Of those who completed the Ottawa Decisional Conflict Score (DCS; n = 356), 52% reported the lowest level of decisional conflict (<25) after using the DST; 43% had a DCS score of 25 to 50, 5.1% had a DCS score of >50 and 2.5% had and DCS score of >75. CONCLUSIONS: The publicly available DST appyornot.org reduced the proportion that was undecided about which treatment they favored and had a modest influence on those with strong treatment preferences. Decisional conflict was not common after use. The use of this DST is now a component of a nationwide implementation program aimed at improving the way surgeons share information about appendicitis treatment options. If its use can be successfully implemented, this may be a model for improving communication about treatment for patients experiencing emergency health conditions.

Safety, Efficacy, and Cost-effectiveness of Outpatient Surgery for Uncomplicated Acute Appendicitis: The PENDI-CSI Randomized Clinical Trial.

OBJECTIVE: To evaluate the safety, efficacy, and cost-effectiveness of outpatient appendectomy in patients with uncomplicated acute appendicitis. BACKGROUND: Given that acute appendicitis is the most common cause of acute abdomen, the introduction of outpatient appendectomy protocols could significantly improve the effectiveness and sustainability of health care systems. METHODS: A total of 300 patients were enrolled from October 2018 to June 2021 in the PENDI-CSI randomized clinical trial: 149 were assigned to the outpatient surgery (OPS) group and 151 to the inpatient surgery (IPS) group, followed by 1 month postoperatively. All patients were aged older than 14 years and had uncomplicated acute appendicitis. Exclusion criteria were pregnancy, neoplasms, inflammatory bowel disease, and high anesthetic risk (ASA IV). The OPS group was discharged from the postanesthesia care unit while the IPS group was admitted. RESULTS: In total, 128 patients in the OPS group (85.9%) were discharged without admission. Predictors whether patients in the OPS group had to be admitted were aged over 31 years [relative risk (RR): 2.42 (1.04-5.65)], hypertension [RR: 6.21 (3.22-11.97)], anesthetic risk II-III [RR: 2.63 (1.17-5.94)], previous abdominal surgery [RR: 3.34 (1.55-7.20)], postoperative pain with visual analog scale >6 [RR: 4.28 (2.67-6.86)], and postoperative fear [RR: 2.2 (1.04-4.67)]. There were no differences in terms of complications, readmissions, and reinterventions, and the perceived quality was similar in both groups. The outpatient modality produced savings of €1 034.97 per patient ( P < 0.001). CONCLUSIONS: Outpatient appendectomy is safe and effective for uncomplicated acute appendicitis. Patient-perceived quality is similar to that of IPS, although it successfully reduces hospital costs compared with inpatient appendectomy.

Two Days Versus Five Days of Postoperative Antibiotics for Complex Appendicitis: Cost Analysis of a Randomized, Noninferiority Trial.

OBJECTIVE: To compare costs for 2 days versus 5 days of postoperative antibiotics within the antibiotics after an aPPendectomy In Complex appendicitis trial.Background:Recent studies suggest that restrictive antibiotic use leads to a significant reduction in hospital stays without compromising patient safety. Its potential effect on societal costs remains underexplored. METHODS: This was a pragmatic, open-label, multicenter clinical trial powered for noninferiority. Patients with complex appendicitis (age ≥ 8 years) were randomly allocated to 2 days or 5 days of intravenous antibiotics after appendectomy. Patient inclusion lasted from June 2017 to June 2021 in 15 Dutch hospitals. The final follow-up was on September 1, 2021. The primary trial endpoint was a composite endpoint of infectious complications and mortality within 90 days. In the present study, the main outcome measures were overall societal costs (comprising direct health care costs and costs related to productivity loss) and cost-effectiveness. Direct health care costs were recorded based on data in the electronic patient files, complemented by a telephone follow-up at 90 days. In addition, data on loss of productivity were acquired through the validated Productivity Cost Questionnaire at 4 weeks after surgery. Cost estimates were based on prices for the year 2019. RESULTS: In total, 1005 patients were evaluated in the "intention-to-treat" analysis: 502 patients were allocated to the 2-day group and 503 to the 5-day group. The mean difference in overall societal costs was - €625 (95% CI: -€ 958 to -€ 278) to the advantage of the 2-day group. This difference was largely explained by reduced hospital stay. Productivity losses were similar between the study groups. Restricting postoperative antibiotics to 2 days was cost-effective, with estimated cost savings of €31,117 per additional infectious complication. CONCLUSIONS: Two days of postoperative antibiotics for complex appendicitis results in a statistically significant and relevant cost reduction, as compared with 5 days. Findings apply to laparoscopic appendectomy in a well-resourced health care setting.

Delayed Versus Early Laparoscopic Appendectomy for Adult Patients With Acute Appendicitis: A Randomized Controlled Trial.

OBJECTIVE: To assess whether delaying appendectomy until the following morning is non-inferior to immediate surgery in those with acute appendicitis presenting at night. BACKGROUND: Despite a lack of supporting evidence, those with acute appendicitis who present at night frequently have surgery delayed until the after morning. METHODS: The delay trial is a noninferiority randomized controlled trial conducted between 2018 and 22 at 2 tertiary care hospitals in Canada. Adults with imaging confirmed acute appendicitis who presented at night (8:00 pm -4:00 am ). Delaying surgery until after 6:00 am was compared with immediate surgery. The primary outcome was 30-day postoperative complications. An a prior noninferiority margin of 15% was deemed clinically relevant. RESULTS: One hundred twenty-seven of the planned 140 patients were enrolled in the Delayed Versus Early Laparoscopic Appendectomy (DELAY) trial (59 in the delayed group and 68 in the immediate group). The two groups were similar at baseline. The mean time between the decision to operate and surgery was longer in the delayed group (11.0 vs 4.4 hours, P < 0.0001). The primary outcome occurred in 6/59 (10.2%) of those in the delayed group versus 15/67 (22.4%) of those in the immediate group ( P = 0.07). The difference between groups met the a priori noninferiority criteria of +15% (risk difference -12.2%, 95% CI: -24.4% to +0.4%, test of noninferiority P < 0.0001). CONCLUSIONS: The DELAY study is the first trial to assess delaying appendectomy in those with acute appendicitis. We demonstrate the noninferiority of delaying surgery until the after morning.

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial.

BACKGROUND: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. METHODS: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. FINDINGS: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI -1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. INTERPRETATION: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. FUNDING: The Netherlands Organization for Health Research and Development.

Role of preoperative in-hospital delay on appendiceal perforation while awaiting appendicectomy (PERFECT): a Nordic, pragmatic, open-label, multicentre, non-inferiority, randomised controlled trial.

BACKGROUND: Appendicectomy remains the standard treatment for appendicitis. No international consensus exists on the surgical urgency for acute uncomplicated appendicitis, and recommendations vary from surgery without delay to surgery within 24 h. Longer in-hospital delay has been thought to increase the risk of perforation and further morbidity. Therefore, we aimed to compare the rate of appendiceal perforation in patients undergoing appendicectomy scheduled to two different urgencies (<8 h vs <24 h). METHODS: In this pragmatic, open-label, multicentre, non-inferiority, parallel, randomised controlled trial in two hospitals in Finland and one in Norway, patients (aged ≥18 years) with presumed uncomplicated acute appendicitis were randomly assigned (1:1) to an appendicectomy scheduled within 8 h or within 24 h to determine whether longer in-hospital delay (time between randomisation and surgical incision) is not inferior to shorter delay. Patients were excluded in cases of pregnancy, suspicion of perforated appendicitis (C-reactive protein level of ≥100 mg/L, fever >38·5°C, signs of complicated appendicitis on imaging studies, or clinical generalised peritonitis), or other reasons requiring prompt surgery. The recruiters were on-duty surgeons who decided to proceed with the appendicectomy. The randomisation sequence was generated using block randomisation with randomly varying block sizes and stratified by hospital districts; neither physicians nor patients were masked to group assignment. The primary outcome was perforated appendicitis diagnosed during surgery analysed in all patients who received an appendicectomy by intention to treat. The absolute difference in rates of perforated appendicitis was compared between the groups. Complications and other safety outcomes were analysed in all patients who received an appendicectomy. A margin of 5 percentage points was used to establish non-inferiority. This trial was registered at ClinicalTrials.gov (NCT04378868) and is closed to accrual. FINDINGS: Between May 18, 2020, and Dec 31, 2022, 2095 patients were assessed for eligibility, of whom 1822 were randomly assigned to appendicectomy scheduled within 8 h (n=914) or 24 h (n=908). After randomisation, 19 (1%) of 1822 patients were excluded due to protocol violation. 1803 patients were included in the intention-to-treat analyses, 985 (55%) of whom were male and 818 (45%) female. Appendiceal perforation rate was similar between groups (77 [8%] of 907 patients assigned to the <8 h group and 81 [9%] of 896 patients assigned to the <24 h group; absolute risk difference 0·6% [95% CI -2·1 to 3·2], p=0·68; risk ratio 1·065, 95% CI 0·790 to 1·435). No significant difference was found between the complication rates within 30 days (66 [7%] of 907 patients in the <8 h group vs 56 [6%] of 896 patients in the <24 h group; difference -1·0% [-3·3 to 1·3]; p=0·39), and no deaths occurred during this follow-up period. INTERPRETATION: In patients with presumed uncomplicated acute appendicitis, scheduling appendicectomy within 24 h does not increase the risk of appendiceal perforation compared with scheduling appendicectomy within 8 h. The results can be used to allocate operating room resources, for example postponing night-time appendicectomy to daytime. FUNDING: The Finnish Medical Foundation, Mary and Georg Ehrnrooth's Foundation, Biomedicum Helsinki Foundation, and the Finnish Government.

Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting.

BACKGROUND: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed. METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses. RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia. CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Single-cell sequencing of the vermiform appendix during development identifies transcriptional relationships with appendicitis in preschool children.

BACKGROUND: The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. RESULTS: Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. CONCLUSIONS: Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.

Exploring S100A8/A9, neopterin, and MMP3 in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is characterized by inflammatory attacks due to overactivation of pyrin inflammasome. This study aimed to investigate the reliability of S100A8/A9, neopterin, and matrix metalloproteinase 3 (MMP3) at monitoring subclinical inflammation and disease activity, and at differentiating FMF attacks from appendicitis, the most common misdiagnosis among FMF patients. Blood samples (n = 75), comprising from FMF patients during an attack (n = 20), the same FMF patients during the attack-free period (n = 14), patients with appendicitis (n = 24), and healthy volunteers (n = 17) were obtained. Duplicate determinations of S100A8/A9, neopterin, and MMP-3 levels were conducted using the enzyme-linked immunosorbent assay (ELISA). FMF patients with and without attack and patients with appendicitis had significantly elevated S100A8/A9 levels compared to healthy volunteers (P-values: < 0.001, 0.036, 0.002, respectively). Patients with appendicitis and FMF patients with and without attack had significantly increased serum neopterin levels compared to healthy volunteers (P-value: < 0.001). MMP3 levels were significantly higher among patients with appendicitis and FMF patients during attack compared to healthy controls (P-values: < 0.001, 0.001). Serum levels of S100A8/A9, neopterin, and MMP3 were increased significantly during attacks compared to attack-free periods among FMF patients (P-values: 0.03, 0.047, 0.007). S100A8/A9 emerges as a valuable marker for monitoring disease activity. Neopterin and S100A8/A9 might help physicians to monitor subclinical inflammation during the attack-free periods of FMF patients. MMP3 might aid in diagnosing FMF attacks when distinguishing between attack and attack-free periods is challenging.

Appendicoscopy using single-operator cholangioscope in the management of acute obstructive appendicitis: a novel alternative (with video).

BACKGROUND AND AIMS: The aim of this study was to investigate the safety and efficacy of appendicoscopy using a single-operator cholangioscope (SOC) for the management of acute obstructive appendicitis. METHODS: This study describes 110 cases of acute obstructive appendicitis managed with the use of appendicoscopy between January 2021 and June 2023. The success rate (technical + clinical), procedure time, time to abdominal pain relief according to a visual analog scale score, postoperative length of hospital stay, and adverse event rates were recorded and analyzed. RESULTS: The technical success rate of appendicoscopy was 96.4%, and the clinical success rate was 91.8%. The mean ± standard deviation procedure time was 20.9 ± 10 minutes. The abdominal pain score at 6 hours after the procedure was ≤3 (visual analog scale method) in 99.1% of patients. The average length of postoperative hospital stay was 3.5 ± 1.5 days. No adverse events occurred. CONCLUSIONS: Appendicoscopy seems to be a feasible and effective alternative therapy for the accurate diagnosis and treatment of acute obstructive appendicitis.

Proteus appendicitidis sp. nov., isolated from the appendiceal pus of an appendicitis patient in Yongzhou, China.

A Gram-negative, facultatively anaerobic, short rod-shaped bacterium, designated as strain HZ0627T, was isolated from the appendiceal pus of a patient with appendicitis in Yongzhou, Hunan, China. This strain was subjected to comprehensive phenotypic, phylogenetic, and genomic analyses using polyphasic taxonomic methods. Phylogenetic analysis of the 16S rRNA gene sequence revealed that this strain belonged to the genus Proteus and the family Morganellaceae, whereas that based on the rpoB gene sequence and phylogenomic analysis demonstrated that this strain was distinctly separated from other type strains of Proteus species. Moreover, whole-genome-based analyses, including in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI), revealed that strain HZ0627T had much lower isDDH rates (24.5-55.6%) and ANI (82.04-93.90%) than those of the thresholds (i.e., 70% and 95%, respectively) for species delineation, when compared to the type strains of other Proteus species. The cellular fatty acid profile of strain HZ0627T was dominated by C16:0 (34.5%), cyclo C17:0 (25.8%), C14:0 (12.6%), C16:1 iso I/14:0 3-OH (7.7%), C18:1ω7c/18:1ω6c (6.5%), and C16:1ω7c/16:1ω6c (4.9%), which clearly differentiated it from the documented type strains of Proteus species. In addition, several specific physiological traits, including optimal growth temperature, tolerance to sodium chloride, and carbon source utilization, differed from those of other Proteus species. Therefore, we propose the name Proteus appendicitidis sp. nov. for strain HZ0627T (= CCTCC AB 2022380T = KCTC 92986T), which represents the type strain of this novel Proteus species.

Exposure to Operative Anesthesia in Childhood and Subsequent Neurobehavioral Diagnoses: A Natural Experiment Using Appendectomy.

BACKGROUND: Observational studies of anesthetic neurotoxicity may be biased because children requiring anesthesia commonly have medical conditions associated with neurobehavioral problems. This study takes advantage of a natural experiment associated with appendicitis to determine whether anesthesia and surgery in childhood were specifically associated with subsequent neurobehavioral outcomes. METHODS: This study identified 134,388 healthy children with appendectomy and examined the incidence of subsequent externalizing or behavioral disorders (conduct, impulse control, oppositional defiant, attention-deficit hyperactivity disorder) or internalizing or mood or anxiety disorders (depression, anxiety, or bipolar disorder) when compared to 671,940 matched healthy controls as identified in Medicaid data between 2001 and 2018. For comparison, this study also examined 154,887 otherwise healthy children admitted to the hospital for pneumonia, cellulitis, and gastroenteritis, of which only 8% received anesthesia, and compared them to 774,435 matched healthy controls. In addition, this study examined the difference-in-differences between matched appendectomy patients and their controls and matched medical admission patients and their controls. RESULTS: Compared to controls, children with appendectomy were more likely to have subsequent behavioral disorders (hazard ratio, 1.04; 95% CI, 1.01 to 1.06; P = 0.0010) and mood or anxiety disorders (hazard ratio, 1.15; 95% CI, 1.13 to 1.17; P < 0.0001). Relative to controls, children with medical admissions were also more likely to have subsequent behavioral (hazard ratio, 1.20; 95% CI, 1.18 to 1.22; P < 0.0001) and mood or anxiety (hazard ratio, 1.25; 95% CI, 1.23 to 1.27; P < 0.0001) disorders. Comparing the difference between matched appendectomy patients and their matched controls to the difference between matched medical patients and their matched controls, medical patients had more subsequent neurobehavioral problems than appendectomy patients. CONCLUSIONS: Although there is an association between neurobehavioral diagnoses and appendectomy, this association is not specific to anesthesia exposure and is stronger in medical admissions. Medical admissions, generally without anesthesia exposure, displayed significantly higher rates of these disorders than appendectomy-exposed patients.

CT of appendicoliths in adult appendicitis: clinical significance and characteristics of overlooked cases.

OBJECTIVES: Accurate computed tomography (CT) identification of appendicoliths in adults with acute appendicitis is crucial as it may preclude nonoperative management due to high risk of failure and complications. This investigation aimed to identify the significance of appendicoliths in acute appendicitis and to evaluate the performance of portovenous-phase (PVP) CT and the consequences of overlooked appendicoliths. METHODS: CT examinations of 324 consecutive patients (mean age 51.9 years, 112 men) with pathologically confirmed acute appendicitis were retrospectively included. Two radiologists independently reviewed the images, and disagreement was resolved by a consensus. RESULTS: Appendicoliths were identified in 134/324 patients, of which 75 had complicated appendicitis. Among 190 patients without appendicoliths, 52 had complicated appendicitis. An appendicolith was independently associated with complicated appendicitis (adjusted odds ratio 2.289; 95% CI: 1.343-3.902; p = 0.002). The larger minimum diameter was significantly associated with complication. The 4.5-/6.0-mm cutoffs for minimum and maximum diameters of appendicoliths demonstrated 82.7%/85.3% sensitivity and 35.6%/33.9% specificity in predicting complications. The PVP alone had 82.1-88.1% sensitivity, respectively per patient and per appendicolith, and a 100% specificity in the detection of appendicoliths, as compared with combined noncontrast and PVP. PVP overlooked 28/237 appendicoliths (11.8%) corresponding to 24/134 patients (17.9%). Of the 24 patients with overlooked appendicoliths, 16 had complicated appendicitis but 14 were correctly categorized by findings other than appendicoliths. In total, 2/127 patients (1.6%) with complicated appendicitis were misdiagnosed as having uncomplicated appendicitis. CONCLUSIONS: Appendicoliths in acute appendicitis were strongly associated with complications. While PVP overlooked some appendicoliths, only 1.6% of complicated appendicitis were misclassified when considering other CT findings. CLINICAL RELEVANCE STATEMENT: This study found a strong association between appendicoliths and complications. Its presence may preclude conservative management. Although portovenous-phase CT overlooked some appendicoliths, the combination with other CT findings allowed correct classification in a vast majority of cases. KEY POINTS: • Accurate identification of appendicoliths is crucial for nonoperative management decisions in adult acute appendicitis. • Appendicoliths are strongly associated with complications in adult acute appendicitis. • Portovenous-phase CT overlooked some appendicoliths, but only a small percentage of patients with complicated appendicitis were misclassified when considering other CT findings.

Using MRI appendicitis scale and DWI for the diagnosis of acute appendicitis in pregnant women.

OBJECTIVES: To assess the performance of MRI scale for the diagnosis of acute appendicitis in pregnant women and to determine the added diagnostic value of diffusion-weighted imaging (DWI). METHODS: From January 2018 to December 2020, 80 patients were included. All MRI were performed with a 1.5-Tesla scanner with anterior array body coil. This analysis included (1) T2-weighted imaging (T2WI), (2) fat-saturated T2WI, and (3) DWI. Two radiologists blinded to the diagnosis recorded their assessment of four findings: appendiceal diameter, appendiceal wall thickness, luminal mucus, and periappendiceal inflammation. The MRI scale of acute appendicitis which ranged from 0 to 4 was determined from these factors. An additional one point was added to the MRI appendicitis scale in those patients with evidence of appendiceal restricted diffusion on DWI. The diagnostic values and predictive factors were computed. RESULTS: Multivariate analysis demonstrated that the calculated MRI appendicitis scale was a significant independent predictor of acute appendicitis with a sensitivity of 96.6%, specificity of 90.2%, and PPV of 84.8%. The odds ratio of appendicitis is increased by 22.3 times for every increase in one point on the MRI appendicitis scale. Therefore, the addition of one point for restricted diffusion in the appendix on DWI imaging can add substantial value, both positive and negative predictive value, towards making an accurate diagnosis of acute appendicitis. CONCLUSIONS: MRI appendicitis scale is an objective and significant independent predictive factor for acute appendicitis in pregnant women. Incorporation of diffusion weighted imaging to MRI can improve diagnosis of acute appendicitis. CLINICAL RELEVANCE STATEMENT: MRI appendicitis scale is an objective and significant independent predictor of acute appendicitis in pregnant women. Incorporation of DWI/ADC map to MRI examinations can improve diagnosis of acute appendicitis in pregnant women. KEY POINTS: • MRI appendicitis scale is an objective and significant independent predictive factor for acute appendicitis in pregnant women. • The odds ratio of appendicitis can be increased by 22.3 times for every increase of one unit in MRI scale. • Incorporation of diffusion-weighted imaging to MRI examinations can add value to the scale (4.2 ± 0.7 vs. 0.7 ± 1.1; p < 0.001) among pregnant women with appendicitis versus pregnant women without appendicitis.

Cost and Late Hospital Care of Publicly Insured Children After Appendectomy.

INTRODUCTION: Immediate complications of appendicitis are common, but the prevalence of long-term complications is uncertain. METHODS: We studied all publicly-insured children in the US with uncomplicated or complicated appendicitis in 2018-2019 using administrative claims. The main outcome was late hospital care defined as hospitalization or abdominal procedure within 180 d of an appendicitis discharge, excluding interval appendectomies. Time to late hospital care was evaluated using Cox regression. We evaluated health-care expenditures arising from appendicitis episodes. RESULTS: Among 95,942 children with appendicitis, 5727 (6.0%) had late hospital care, with 5062 requiring rehospitalization and 2012 (2.1%) surgery. The median time to late hospital care was 10 d (interquartile range 4-33). Age under 5 y (compared with >14 y, hazard ratio [HR] 1.88, 95% confidence interval [CI] 1.70-2.08), complex chronic conditions (HR 2.35, 95% CI 2.13-2.59), and complicated appendicitis (HR 2.81, 95% CI 2.67, 2.96) were each associated with time to late hospital care. Expenditures over 180 d were a median $6553 and $19,589 respectively in those requiring no late hospital care versus those requiring it (P < 0.001). CONCLUSIONS: Late hospital care is uncommon in pediatric appendicitis but is costly. Prevention efforts should be targeted to the youngest, most complex children, and those with complicated appendicitis at presentation.

Using Consumer Wearable Devices to Profile Postoperative Complications After Pediatric Appendectomy.

INTRODUCTION: Markers of postoperative recovery in pediatric patients are difficult for parents to evaluate after hospital discharge, who use subjective proxies to assess recovery and the onset of complications. Consumer-grade wearable devices (e.g., Fitbit) generate objective recovery data in near real time and thus may provide an opportunity to remotely monitor postoperative patients and identify complications beyond the initial hospitalization. The aim of this study was to use daily step counts from a Fitbit to compare recovery in patients with complications to those without complications after undergoing appendectomy for complicated appendicitis. METHODS: Children ages 3-17 years old undergoing laparoscopic appendectomy for complicated appendicitis were recruited. Patients wore a Fitbit device for 21 d after operation. After collection, patient data were included in the analysis if minimum wear-time criteria were achieved. Postoperative complications were identified through chart review, and step count trajectories for patients recovering with and without complications were compared. Additionally, to account for the patients experiencing a complication on different postoperative days, median daily step count for pre- and post-complication were analyzed. RESULTS: Eighty-six patients with complicated appendicitis were enrolled in the study, and fourteen children developed a postoperative complication. Three patients were excluded because they did not meet the minimum wear time requirements. Complications were divided into abscesses (n = 7, 64%), surgical site infections (n = 2, 18%), and other, which included small bowel obstruction and Clostridioides difficile infection (n = 2, 18%). Patients presented with a complication on mean postoperative day 8, while deviation from the normative recovery trajectory was evident 4 d prior. When compared to children with normative recovery, the patients with surgical complications experienced a slower increase in step count postoperatively, but the recovery trajectory was specific to each complication type. When corrected for day of presentation with complication, step count remained low prior to the discovery of the complication and increased after treatment resembling the normative recovery trajectory. CONCLUSIONS: This study profiled variations from the normative recovery trajectory in patients with complication after appendectomy for complicated appendicitis, with distinct trajectory patterns by complication type. Our findings have potentially profound clinical implications for monitoring pediatric patients postoperatively, particularly in the outpatient setting, thus providing objective data for potentially earlier identification of complications after hospital discharge.

Using Wearable Devices to Profile Demographic-Specific Recovery After Pediatric Appendectomy.

INTRODUCTION: Counseling patients and parents about the postoperative recovery expectations for physical activity after pediatric appendectomy varies significantly and is not specific to patients' demographic characteristics. Consumer wearable devices (CWD) can be used to objectively assess patients' normative postoperative recovery of physical activity. This study aimed to develop demographic-specific normative physical activity recovery trajectories using CWD in pediatric patients undergoing appendectomy. METHODS: Children ages 3-18 y old undergoing laparoscopic appendectomy for acute appendicitis were recruited. Patients wore a Fitbit device for 21 d postoperatively and daily step counts were measured. Patients with postoperative complications were excluded. Segmented regression models were fitted and time-to-plateau was estimated for patients with simple and complicated appendicitis separately for each age group, sex, race/ethnicity, and body mass index category. RESULTS: Among 147 eligible patients; 76 (51.7%) were female, 86 (58.5%) were in the younger group, and 79 (53.7%) had complicated appendicitis. Patients 3-11 y old demonstrated a faster trajectory to a physical activity plateau compared to those 12-18 in both simple (postoperative day [POD] 9 versus POD 17) and complicated appendicitis (POD 17 versus POD 21). Males and females had a similar postoperative recovery trajectory in simple and complicated appendicitis. There was no clear pattern differentiating trajectories based on race/ethnicity. Overweight/obese patients demonstrated a slower recovery trajectory in simple appendicitis. CONCLUSIONS: This study demonstrates that factors other than the disease itself, such as age, may affect recovery, suggesting the need for more tailored discharge instructions. CWDs can improve our understanding of recovery and allow for better data-driven counseling perioperatively.

Clinical Characteristics of Avoidable Patient Transfers for Suspected Pediatric Appendicitis.

INTRODUCTION: Pediatric surgical care is becoming increasingly regionalized, often resulting in limited access. Interfacility transfers pose a significant financial and emotional burden to when they are potentially avoidable. Of transferred patients, we sought to identify clinical factors associated with avoidable transfers in pediatric patients with suspected appendicitis. METHODS: We performed a single-center retrospective study at an academic tertiary referral children's hospital in an urban setting. We included children who underwent interfacility transfer to our center with a transfer diagnosis of appendicitis from July 1, 2021 to June 30, 2023. Encounters were designated as either an appropriate transfer (underwent appendectomy) or an avoidable transfer (did not undergo appendectomy). Encounters treated nonoperatively for complicated appendicitis were excluded. Bivariate analysis was performed using Mann-Whitney test and chi-square tests. RESULTS: A total of 444 patients were included: 71.2% were classified as appropriate transfers and 28.8% as avoidable transfers. Patients with avoidable transfer were younger compared to those in the appropriate transfer cohort (median age 9 y, interquartile range: 7-13 versus 11 y, interquartile range: 8-14; P < 0.001). Avoidable transfers less frequently presented with the typical symptoms of fever, migratory abdominal pain, anorexia, and nausea/emesis (P = 0.005). Avoidable transfers also reported shorter symptom duration (P = 0.040) with lower median white blood cell count (P < 0.001), neutrophil percentage (P < 0.001), and C-reactive protein levels (P < 0.003). Avoidable transfers more frequently underwent repeat imaging upon arrival (42.9% versus 12.7%, P < 0.001). CONCLUSIONS: These findings highlight the importance of clinical history in children with suspected appendicitis. Younger patients without typical symptoms of appendicitis, those with a shorter duration of symptoms, and lower serum inflammatory markers may benefit from close observation without transfer.