Open AccessArticle Outcomes and Predictors of Mortality in Perforated Versus Non-Perforated Peptic Ulcer Disease: A U.S. Nationwide Propensity-Matched Analysis, 2016–2021 by Abdullah Sultany Abdullah Sultany Scilit Preprints.org Google Scholar 1,*, Adishwar Rao Adishwar Rao Scilit Preprints.org Google Scholar 1, Amlish Gondal Amlish Gondal Scilit Preprints.org Google Scholar 2, Abhinay Theli Abhinay Theli Scilit Preprints.org Google Scholar 1, Rahul Chikatimalla Rahul Chikatimalla Scilit Preprints.org Google Scholar 3, Mohamed A. Omar Mohamed A. Omar Scilit Preprints.org Google Scholar 4, Rewanth Katamreddy Rewanth Katamreddy Scilit Preprints.org Google Scholar 2, Raja Chandra Chakinala Raja Chandra Chakinala Scilit Preprints.org Google Scholar 2, Mohammad Sulaiman Sultany Mohammad Sulaiman Sultany Scilit Preprints.org Google Scholar 5, Dushyant Singh Dahiya Dushyant Singh Dahiya Scilit Preprints.org Google Scholar Dr. Dushyant Singh Dahiya is a Gastroenterology, Hepatology and Motility Fellow at the University of [...] Read more 6, Subash Ghimire Subash Ghimire Scilit Preprints.org Google Scholar 2 and Michael J. Georgetson Michael J. Georgetson Scilit Preprints.org Google Scholar 2 1 Department of Internal Medicine, Guthrie Robert Packer Hospital, 1 Guthrie Square, Sayre, PA 18840, USA 2 Department of Gastroenterology and Hepatology, Guthrie Robert Packer Hospital, Sayre, PA 18840, USA 3 Department of Internal Medicine, University of Texas Health Science Center, Tyler, TX 75708, USA 4 Department of Gastroenterology, University of Kansas, Wichita, KS 67214, USA 5 Department of General and Bariatric Surgery, Guthrie Robert Packer Hospital, Sayre, PA 18840, USA 6 Division of Gastroenterology, Hepatology & Motility, School of Medicine, University of Kansas, Kansas City, KS 66160, USA * Author to whom correspondence should be addressed. J. Clin. Med. 2026, 15(11), 4358; https://doi.org/10.3390/jcm15114358 (registering DOI) Submission received: 9 May 2026 / Revised: 28 May 2026 / Accepted: 2 June 2026 / Published: 4 June 2026 Abstract Background/Objectives: Perforated peptic ulcer (PPU) represents a surgical emergency with substantial morbidity and mortality. Despite declining overall peptic ulcer disease (PUD) incidence, contemporary population-based data comparing outcomes between perforated and non-perforated PUD remain limited, particularly during the COVID-19 pandemic. This study aimed to characterize the clinical and economic burden of PPU and identify independent predictors of adverse outcomes. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (2016–2021), identifying 2,561,379 weighted hospitalizations for PUD. Hospitalizations were stratified by the presence ( n = 207,970, 8.1%) or absence ( n = 2,353,409, 91.9%) of perforation. The primary outcome was in-hospital mortality; secondary outcomes included sepsis, septic shock, acute kidney injury (AKI), prolonged length of stay (≥7 days), and high healthcare costs (≥ $12,000). We performed 1:1 propensity score matching and multivariable logistic regression to assess independent predictors of adverse outcomes in the PPU cohort. Results: After propensity matching, PPU demonstrated significantly higher mortality than non-perforated PUD (7.2% vs. 3.0%, p < 0.001), along with increased rates of sepsis (21.8% vs. 8.2%, p < 0.001), septic shock (12.9% vs. 3.5%, p < 0.001), and AKI (29.5% vs. 22.8%, p < 0.001). Nearly half (45.6%) of PPU admissions exceeded 7 days, and 69.2% incurred costs ≥ $12,000. Among PPU hospitalizations, multivariable analysis identified age ≥ 65 years (aOR 5.79, 95% CI 4.60–7.28), liver cirrhosis (aOR 1.93, 95% CI 1.62–2.30), chronic heart failure (aOR 1.73, 95% CI 1.56–1.92), and concurrent COVID-19 infection (aOR 4.35, 95% CI 3.46–5.47) as independent predictors of mortality. Chronic kidney disease strongly predicted AKI (aOR 2.81, 95% CI 2.64–2.98). Mortality increased from 6.9% (2016) to 8.0% (2021) in PPU hospitalizations ( p < 0.001 for trend), with higher rates observed during the 2020 to 2021 period that coincided with the COVID-19 pandemic. Conclusions: Perforation complicates approximately 8% of hospitalized PUD cases but accounts for disproportionate mortality, sepsis, organ failure, and healthcare costs. Older age, cirrhosis, heart failure, and chronic kidney disease identify high-risk PPU patients requiring intensive monitoring and aggressive management. These findings support risk-stratified approaches focused on timely diagnosis, source control, and sepsis management to reduce the clinical and economic burden of PPU. Keywords: peptic ulcer disease; perforated peptic ulcer; mortality; sepsis; acute kidney injury; healthcare costs; National Inpatient Sample; COVID-19; risk stratification; emergency surgery 1. Introduction Sepsis is a critical determinant of outcomes in gastrointestinal surgical emergencies and is a frequent complication of PPU. In the United States, the incidence, mortality, and costs associated with sepsis have increased, particularly among older adults. From 2019 to 2021, sepsis-related in-hospital mortality among adults aged 65 or older increased by 37.5% [ 9]. Abdominal sepsis related to PPU has reported mortality rates of 18% to 20%; however, previous studies have rarely isolated the risk specific to perforation [ 10]. Existing analyses of the National Inpatient Sample (NIS) have often grouped perforation with other complications of peptic ulcer disease, such as hemorrhage, which limits accurate estimation of outcomes attributable specifically to perforation [ 11]. Few contemporary studies have directly compared perforated and non-perforated PUD within a single nationally representative cohort, and the adjusted associations between perforation and sepsis, septic shock, acute kidney injury (AKI), length of stay, hospital costs, and pandemic-era mortality trends have not been systematically examined. By isolating perforation without concurrent hemorrhage and applying both propensity score matching and multivariable adjustment that account for patient and hospital-level characteristics, the present study addresses these gaps and provides contemporary, perforation-specific estimates spanning the pre-pandemic and COVID-19 periods. This study uses NIS data from 2016 to 2021 to compare in-hospital outcomes and resource use between PUD admissions with and without perforation. The objectives are to: (1) estimate the adjusted odds of mortality, sepsis or septic shock, AKI, prolonged LOS, and high hospital charges and costs associated with perforation; (2) identify predictors of adverse outcomes among PPU patients; and (3) assess trends in these outcomes before (2016–2019) and during (2020–2021) the COVID-19 pandemic. We hypothesize that: (i) PPU is independently associated with increased odds of mortality and major complications; (ii) among PPU patients, older age, cirrhosis, heart failure, and concurrent COVID-19 infection predict adverse outcomes; and (iii) clinical and economic outcomes worsened during the COVID-19 era compared with the pre-pandemic baseline. 2. Materials and Methods 2.1. Data Source and Cohort Selection We queried the NIS database provided by the Agency for Healthcare Research and Quality (AHRQ) under the Healthcare Cost and Utilization Project (HCUP) to perform a retrospective observational study [ 12]. The NIS is the largest all-payer inpatient database publicly available for outcomes research in the United States, comprising a stratified 20% sample of discharges from all participating community hospitals, from which national estimates are derived using survey weights. We identified all hospitalizations for peptic ulcer disease during the study period (2016–2021) using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes ( Supplementary Table S1). We excluded encounters for patients under 18 years of age and those with missing data on age, sex, or in-hospital mortality. The cohort was then stratified into two groups based on the presence or absence of perforation. To isolate perforation as the exposure of interest, we defined the perforated group using ICD-10-CM codes denoting peptic ulcer with perforation but without concurrent hemorrhage. Codes denoting combined hemorrhage and perforation were not included, in order to avoid misattribution of bleeding-related outcomes to perforation and to define a clinically homogeneous perforation cohort. The complete code set used to define the overall cohort, the perforation subgroup, comorbidities, and outcomes is provided in Supplementary Table S1. 2.2. Study Variables and Outcomes We examined demographic characteristics, hospital-level characteristics, comorbidities, and clinical and economic outcomes. Hospital-level characteristics included hospital region, location and teaching status, bed size, and primary expected payer. Total hospital charges were adjusted for annual inflation using the Consumer Price Index. Comorbidities comprised cardiovascular and cerebrovascular conditions (hyperlipidemia, hypertension, heart failure, prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass grafting, prior stroke, and smoking/tobacco use), endocrine and metabolic conditions (diabetes mellitus, obesity, hypothyroidism), renal disease (chronic kidney disease/end-stage renal disease), pulmonary conditions (chronic obstructive pulmonary disease, obstructive sleep apnea, and COVID-19), liver disease (alcoholic liver disease, toxic liver disease, and liver cirrhosis/fibrosis), and nutritional anemia. The primary outcome was in-hospital mortality. Secondary outcomes included sepsis, septic shock, acute kidney injury (AKI), other/unspecified shock, prolonged length of stay (≥7 days), and significant economic burden, defined using prespecified pragmatic analytic thresholds (rather than externally validated clinical cutoffs) of total charges ≥ $40,000 and total costs ≥ $12,000. Total charges and costs were dichotomized at these prespecified thresholds as pragmatic markers of high-resource hospitalizations. Because hospital charges and costs are highly right-skewed, dichotomization provides a clinically interpretable basis for comparison between groups. 2.3. Statistical Analysis We assessed the distribution of continuous variables using histograms and quantile plots. Categorical data were summarized as weighted counts and percentages, and continuous data as means. Categorical variables were compared using the Pearson chi-square test and continuous variables using the t test. All analyses incorporated the discharge weight (DISCWT), hospital cluster, and stratum variables provided by HCUP to generate nationally representative estimates that account for the complex survey design. The NIS contains minimal missingness for the primary outcome and core analytic variables; encounters with missing data on age, sex, or mortality were excluded as described above, and no imputation was performed. To minimize confounding from baseline differences between perforated and non-perforated groups, we estimated propensity scores using a logistic regression model with perforation status as the dependent variable. The propensity score model included all demographic characteristics, comorbidities, and hospital-level characteristics (region, location/teaching status, bed size, and primary payer); the complete covariate list is provided in Supplementary Table S2. We performed 1:1 nearest-neighbor matching without replacement using the psmatch2 command in Stata, applying a caliper of 0.1 of the propensity score and restricting matches to the region of common support. These specifications yielded 40,364 matched pairs. The relatively conservative caliper and common-support restriction, rather than a limited donor pool, account for the proportion of perforated encounters not retained in the matched cohort; matching without replacement was feasible given the large donor pool of non-perforated cases ( n = 2,353,409) relative to perforated cases ( n = 207,970). Covariate balance before and after matching was assessed using the standardized percent bias for each covariate and overall summary measures (mean and median absolute bias and Rubin’s B), with standardized differences below 10% considered indicative of adequate balance ( Supplementary Table S3 and Supplementary Figure S1). Within the perforated PUD cohort, we performed multivariable logistic regression for each clinical outcome to identify independent predictors, reporting adjusted odds ratios (aOR) with 95% confidence intervals (CI). To verify the stability of these models, we examined multicollinearity among predictors using variance inflation factors (VIF); all values were well below conventional thresholds of concern ( Supplementary Table S4). Temporal trends in in-hospital mortality across the study period were evaluated using the Cochran–Armitage test for trend. Statistical significance was defined as a two-sided p-value < 0.05. All analyses were performed using Stata version 18 (StataCorp LLC, College Station, TX, USA). 2.4. Institutional Review Board Approval Institutional Review Board review was not required because the study used publicly available, fully de-identified data. In accordance with HCUP data use policies, cells representing fewer than 11 observations were not reported. 3. Results 3.1. Demographics and Comorbidity Burden We analyzed 2,561,379 weighted hospitalizations for peptic ulcer disease, of which 207,970 (8.1%) involved perforation and 2,353,409 (91.9%) did not. Hospitalizations with perforation were, on average, slightly younger (mean age 63.9 vs. 65.7 years, p < 0.001), more often female (51.7% vs. 49.2%, p < 0.001), and differed significantly by race/ethnicity (White: 71.3% vs. 68.5%; Black: 13.2% vs. 14.5%; Hispanic: 8.4% vs. 9.9%; p < 0.001). Compared with non-perforated hospitalizations, those with perforation had lower proportions of several cardiometabolic comorbidities, including hyperlipidemia (31.4% vs. 40.1%, p < 0.001), hypertension (59.7% vs. 69.2%, p < 0.001), chronic heart failure (15.3% vs. 20.5%, p < 0.001), and diabetes mellitus (24.0% vs. 30.9%, p < 0.001). Conversely, smoking/tobacco use was more prevalent in the perforation group (43.9% vs. 41.5%, p < 0.001) ( Figure 1; Table 1). 3.2. Hospital Metrics Medicare was the predominant payer across the cohort, although hospitalizations with perforation had relatively lower Medicare coverage (53.8% vs. 60.0%, p < 0.001) and higher proportions of private insurance (22.3% vs. 19.4%, p < 0.001) and self-pay (6.0% vs. 4.2%, p < 0.001). Hospitalizations with perforation incurred substantially higher inflation-adjusted total charges (mean $137,815 vs. $90,390) and total costs (mean $32,245 vs. $20,710), and a longer mean length of stay (9.3 vs. 6.6 days; all p < 0.001). 3.4. Mortality Trends In-hospital mortality rose across the study period in both groups. Among hospitalizations with perforation, mortality increased from 6.7% in 2019 to 8.0% in 2020 and 2021, with an overall upward trend from 6.9% in 2016 to 8.0% in 2021 ( p < 0.001 for trend). Mortality in non-perforated PUD similarly increased from 2.7% in 2016 to 4.2% in 2021 ( p < 0.001 for trend). The increases in both groups were greater during the 2020 to 2021 period, which coincided with the COVID-19 pandemic ( Figure 3; Table 4). 4. Discussion This nationwide analysis of more than 2.5 million peptic ulcer disease (PUD) hospitalizations demonstrates that perforation, although complicating only 8% of admissions, carries a disproportionate burden of mortality, organ failure, and resource use. After rigorous propensity score matching that balanced demographic, comorbidity, and hospital-level characteristics, hospitalizations with perforated peptic ulcer (PPU) had more than double the in-hospital mortality of non-perforated PUD (7.2% vs. 3.0%), together with markedly higher rates of sepsis, septic shock, acute kidney injury (AKI), prolonged hospitalization, and high-cost care. Within the perforated cohort, advanced age, liver cirrhosis, chronic heart failure, chronic kidney disease, COPD, and concurrent COVID-19 infection independently predicted adverse outcomes. These mortality and morbidity estimates align with the contemporary literature. Reported short-term mortality after PPU ranges widely, with population-based and pooled estimates of 30-day mortality reaching approximately 23.5%, and our in-hospital figure of 7.2% falls within the lower end of this range, consistent with the shorter observation window inherent to inpatient administrative data [ 13, 14, 15]. The persistent burden of perforation despite declining overall PUD incidence echoes global epidemiologic data showing that, although age-standardized PUD rates have fallen over recent decades, the decline has plateaued and complications continue to affect an aging population exposed to nonsteroidal anti-inflammatory drugs, antithrombotic agents, and Helicobacter pylori [ 15, 16]. A recent global multicenter study of surgery for PPU similarly reported substantial 30-day morbidity and mortality with a median hospital stay comparable to that observed here [ 17]. Notably, patients with perforation in our cohort were younger and carried fewer documented cardiometabolic comorbidities than those without perforation, yet experienced substantially worse outcomes. This suggests that perforation is strongly associated with the excess risk, independent of baseline comorbidity burden, rather than the excess risk being explained by comorbidity alone. Our study extends prior National Inpatient Sample analyses, which have frequently grouped perforation with other PUD complications and thereby obscured perforation-specific risk [ 11]. By isolating perforation without concurrent hemorrhage and applying both propensity matching and multivariable modeling adjusted for hospital-level factors, we provide contemporary, adjusted estimates of the independent association between perforation and a comprehensive set of clinical and economic outcomes, including the pandemic-era period. The rising mortality we observed parallels recent national data on increasing peptic ulcer disease-related mortality in the United States [ 24]. These temporal findings warrant cautious interpretation. Mortality rose in both groups, with the steepest increases during the 2020 to 2021 pandemic period, and concurrent COVID-19 infection was associated with a more than fourfold increase in the adjusted odds of death, although our design cannot establish causation. During the pandemic, emergency surgical services faced delayed presentations and reduced operative volumes, and surgical mortality rose irrespective of confirmed COVID-19 status [ 25]. Delayed presentation may lead to greater peritoneal contamination and more advanced sepsis, and COVID-19 itself can compound this insult through endothelial dysfunction, hypercoagulability, and dysregulated inflammation, particularly in older adults [ 26]. The parallel rise among non-perforated hospitalizations points to a system-wide effect rather than one specific to perforation, and administrative data cannot distinguish death caused by COVID-19 from death merely occurring with incidental infection. Prior institutional analyses of peptic ulcer perforation during the pandemic similarly reported altered management and outcomes [ 27, 28], although emergency surgical care was largely maintained. These temporal associations should be regarded as hypothesis-generating. Several comorbidities, including smoking, hypertension, hyperlipidemia, prior percutaneous coronary intervention, and nutritional anemia, showed paradoxical inverse associations with mortality. These are unlikely to reflect multicollinearity, as all variance inflation factors were well below conventional thresholds (mean 1.23; Supplementary Table S4). Instead, they most likely reflect residual confounding and selection effects inherent to a disease-restricted cohort. Conditioning on an index event such as perforation can make established risk factors appear spuriously protective through collider (index-event) bias, as described for the apparent protective effect of smoking in such samples [ 29]. Survivorship bias may also contribute, as the frailest patients with heavy comorbidity burden may not survive to present with perforation. These associations should not be interpreted as causal or protective. 5. Conclusions In this nationwide cohort, perforation complicated approximately 8% of PUD hospitalizations but accounted for a disproportionate burden of mortality, sepsis, organ failure, prolonged hospitalization, and cost, with associations that persisted after propensity matching and multivariable adjustment. Advanced age, liver cirrhosis, chronic heart failure, chronic kidney disease, COPD, and concurrent COVID-19 infection identified patients at particularly high risk. The rise in mortality observed during the 2020 to 2021 period, which cannot be attributed to COVID-19 on the basis of this descriptive analysis, may reflect the vulnerability of time-sensitive emergency surgical care to systemic disruption. Collectively, these findings support early recognition, prompt source control, aggressive sepsis management, and risk-stratified care for patients with perforated peptic ulcers, and they suggest that maintaining resilient emergency surgical pathways may be important during periods of health-system strain. Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm15114358/s1, Table S1: ICD-10-CM diagnosis codes used to define the peptic ulcer disease cohort, the perforated subgroup, comorbidities, and outcomes; Table S2: Covariates included in the propensity score model and the multivariable regression models; Table S3: Standardized percent bias for all covariates before and after 1:1 propensity score matching, with overall summary measures (mean and median absolute bias and Rubin’s B); Table S4: Variance inflation factors for the multivariable logistic regression models; Table S5: Complete multivariable logistic regression results for all five outcomes (in-hospital mortality, sepsis, septic shock, acute kidney injury, and other/unspecified shock); Figure S1: Propensity score distributions in the perforated and non-perforated groups before and after 1:1 nearest-neighbor matching. Author Contributions Conceptualization, A.S. and M.J.G.; methodology, A.S., A.R. and M.J.G.; software, A.R.; validation, A.S., A.R. and A.G.; formal analysis, A.R. and A.S.; investigation, A.S., A.R., A.G., A.T., R.C., M.A.O., R.K., R.C.C., M.S.S., D.S.D., S.G. and M.J.G.; resources, M.J.G.; data curation, A.R. and A.S.; writing—original draft preparation, A.S.; writing—review and editing, A.S., A.R., A.G., A.T., R.C., M.A.O., R.K., R.C.C., M.S.S., D.S.D., S.G. and M.J.G.; visualization, A.R. and A.S.; supervision, M.J.G. and S.G.; project administration, A.S. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Institutional Review Board Statement This retrospective study utilized publicly available data from the National Inpatient Sample (NIS) database. All included data have been fully de-identified and anonymized, and no private or identifiable individual information is retained. Since the study did not involve recruitment, intervention, or direct contact with human subjects, Institutional Review Board review was exempted. Informed Consent Statement This study used de-identified data from the National Inpatient Sample, and informed consent was not required. Data Availability Statement The data presented in this study are available from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) at https://www.hcup-us.ahrq.gov/nisoverview.jsp (accessed on 5 April 2026). These data were derived from a resource available in the public domain: HCUP National Inpatient Sample (NIS), Agency for Healthcare Research and Quality (AHRQ). Access to the NIS requires completion of the HCUP Data Use Agreement training. Conflicts of Interest The authors declare no conflicts of interest. References Almadi, M.A.; Lu, Y.; Alali, A.A.; Barkun, A.N. Peptic ulcer disease. Lancet 2024, 404, 68–81. 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[ Google Scholar] [ CrossRef] Patel, S.; Kalra, D.; Kacheriwala, S.; Shah, M.; Duttaroy, D. Validation of prognostic scoring systems for predicting 30-day mortality in perforated peptic ulcer disease. Turk. J. Surg. 2019, 35, 252. [ Google Scholar] [ CrossRef] Rivai, M.I.; Suchitra, A.; Janer, A. Evaluation of clinical factors and three scoring systems for predicting mortality in perforated peptic ulcer patients, a retrospective study. Ann. Med. Surg. 2021, 69, 102735. [ Google Scholar] [ CrossRef] Figure 1. Comorbidity prevalence in perforated versus non-perforated peptic ulcer disease. Figure 1. Comorbidity prevalence in perforated versus non-perforated peptic ulcer disease. Figure 2. Propensity-matched clinical and economic outcomes ( n = 40,364 pairs). Figure 2. Propensity-matched clinical and economic outcomes ( n = 40,364 pairs). Figure 3. In-hospital mortality trends, 2016 to 2021. Figure 3. In-hospital mortality trends, 2016 to 2021. Table 1. Baseline characteristics of hospitalizations with peptic ulcer disease, stratified by perforation status (weighted). Table 1. Baseline characteristics of hospitalizations with peptic ulcer disease, stratified by perforation status (weighted). Characteristic Perforation ( n = 207,970) No Perforation ( n = 2,353,409) p-Value Age (years), mean 63.9 65.7 <0.001 Age group <0.001 18–44 26,710 (12.8) 252,300 (10.7) 45–64 73,760 (35.5) 762,545 (32.4) ≥65 107,500 (51.7) 1,338,564 (56.9) Female sex 107,540 (51.7) 1,157,900 (49.2) <0.001 Race/ethnicity <0.001 White 144,015 (71.3) 1,568,384 (68.5) Black 26,755 (13.2) 332,170 (14.5) Hispanic 16,895 (8.4) 227,190 (9.9) Asian/Pacific Islander 7585 (3.8) 84,000 (3.7) Native American 1475 (0.7) 14,660 (0.6) Other 5340 (2.6) 62,810 (2.7) Primary payer <0.001 Medicare 111,650 (53.8) 1,410,574 (60.0) Medicaid 30,550 (14.7) 319,535 (13.6) Private 46,320 (22.3) 455,350 (19.4) Self-pay 12,435 (6.0) 98,020 (4.2) No charge 1015 (0.5) 10,075 (0.4) Other 5735 (2.8) 56,835 (2.4) Hospital region <0.001 Northeast 33,500 (16.1) 400,935 (17.0) Midwest 45,815 (22.0) 537,240 (22.8) South 83,610 (40.2) 930,825 (39.6) West 45,045 (21.7) 484,409 (20.6) Location/teaching status <0.001 Rural 19,250 (9.3) 180,495 (7.7) Urban non-teaching 45,500 (21.9) 512,060 (21.8) Urban teaching 143,220 (68.9) 1,660,855 (70.6) Hospital bed size 0.030 Small 43,690 (21.0) 482,644 (20.5) Medium 62,225 (29.9) 698,024 (29.7) Large 102,055 (49.1) 1,172,740 (49.8) Comorbidities Hyperlipidemia 65,215 (31.4) 944,005 (40.1) <0.001 Hypertension 124,165 (59.7) 1,629,494 (69.2) <0.001 Chronic heart failure 31,750 (15.3) 483,250 (20.5) <0.001 Prior myocardial infarction 9490 (4.6) 164,655 (7.0) <0.001 Prior PCI 9420 (4.5) 157,545 (6.7) <0.001 Prior CABG 415 (0.2) 6915 (0.3) <0.001 Obesity 33,055 (15.9) 385,425 (16.4) 0.012 Smoking/tobacco use 91,340 (43.9) 976,385 (41.5) <0.001 COPD 34,090 (16.4) 438,895 (18.6) <0.001 Obstructive sleep apnea 11,265 (5.4) 163,290 (6.9) <0.001 Prior stroke 14,675 (7.1) 238,495 (10.1) <0.001 Alcoholic liver disease 725 (0.3) 11,325 (0.5) <0.001 Liver cirrhosis/fibrosis 6930 (3.3) 102,930 (4.4) <0.001 Toxic liver disease 35 (0.0) 445 (0.0) 0.764 Diabetes mellitus 49,835 (24.0) 727,360 (30.9) <0.001 Hypothyroidism 23,420 (11.3) 312,295 (13.3) <0.001 Nutritional anemia 19,290 (9.3) 380,875 (16.2) <0.001 COVID-19 2410 (1.2) 26,770 (1.1) 0.696 Data are presented as n (%) unless otherwise indicated. Percentages are weighted. PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting; COPD = chronic obstructive pulmonary disease. p-values from Pearson chi-square (categorical) or t test (continuous). Table 2. Crude and propensity-matched clinical and economic outcomes, perforated versus non-perforated peptic ulcer disease. Table 2. Crude and propensity-matched clinical and economic outcomes, perforated versus non-perforated peptic ulcer disease. Outcome Crude—Perf ( n = 207,970) Crude—No Perf ( n = 2,353,409) p Matched—Perf ( n = 40,364) Matched—No Perf ( n = 40,364) p In-hospital mortality 15,020 (7.2) 76,505 (3.3) <0.001 2900 (7.2) 1212 (3.0) <0.001 Sepsis 45,320 (21.8) 200,500 (8.5) <0.001 8816 (21.8) 3303 (8.2) <0.001 Septic shock 26,780 (12.9) 84,965 (3.6) <0.001 5191 (12.9) 1401 (3.5) <0.001 Acute kidney injury 61,320 (29.5) 612,685 (26.0) <0.001 11,902 (29.5) 9184 (22.8) <0.001 Other/unspecified shock 7210 (3.5) 83,725 (3.6) 0.344 1401 (3.5) 1281 (3.2) <0.001 Prolonged LOS (≥7 days) 94,770 (45.6) 694,625 (29.5) <0.001 18,394 (45.6) 11,038 (27.4) <0.001 Total charges ≥ $40,000 43,830 (21.1) 263,385 (11.2) <0.001 8458 (20.9) 4180 (10.4) <0.001 Total cost ≥ $12,000 143,910 (69.2) 1,128,720 (48.0) <0.001 27,910 (69.2) 18,298 (45.3) <0.001 Data are n (%), weighted. Matched cohort derived from 1:1 nearest-neighbor propensity score matching (caliper 0.1, common support). LOS = length of stay. Table 3. Independent predictors of in-hospital mortality and sepsis among hospitalizations with perforated peptic ulcer disease (multivariable logistic regression). Table 3. Independent predictors of in-hospital mortality and sepsis among hospitalizations with perforated peptic ulcer disease (multivariable logistic regression). Predictor In-Hospital Mortality aOR (95% CI) Sepsis aOR (95% CI) Age group 45–64 2.80 (2.26–3.48) 1.52 (1.39–1.66) ≥65 5.79 (4.60–7.28) 1.73 (1.57–1.91) Female sex 0.91 (0.84–0.99) 0.92 (0.87–0.96) Heart failure 1.73 (1.56–1.92) 1.51 (1.41–1.62) Chronic kidney disease 1.41 (1.27–1.56) 1.14 (1.06–1.22) Liver cirrhosis/fibrosis 1.93 (1.62–2.30) 1.30 (1.14–1.48) COPD 1.55 (1.40–1.72) 1.53 (1.43–1.63) Diabetes mellitus 1.04 (0.95–1.15) 1.13 (1.07–1.21) Obesity 0.99 (0.89–1.11) 1.28 (1.19–1.37) COVID-19 4.35 (3.46–5.47) 2.35 (1.93–2.86) Hyperlipidemia 0.65 (0.59–0.72) 0.73 (0.69–0.77) Hypertension 0.77 (0.70–0.84) 0.88 (0.83–0.93) Smoking/tobacco use 0.57 (0.52–0.62) 0.74 (0.70–0.78) Prior PCI 0.54 (0.42–0.69) 0.49 (0.42–0.57) Nutritional anemia 0.67 (0.57–0.78) 0.74 (0.68–0.82) aOR = adjusted odds ratio; CI = confidence interval. Models adjusted for demographics, comorbidities, and hospital-level characteristics (region, teaching status, bed size, primary payer). Full results for all outcomes, including septic shock, acute kidney injury, and other/unspecified shock, are provided in Supplementary Table S5. Inverse associations observed for some comorbidities (for example, smoking, hyperlipidemia, and hypertension) should not be interpreted as causal or protective; they most likely reflect residual confounding and selection effects, including index-event and survivorship bias, in this disease-restricted cohort. Table 4. In-hospital mortality trends by year, 2016–2021 (%). Table 4. In-hospital mortality trends by year, 2016–2021 (%). Group 2016 2017 2018 2019 2020 2021 p-Trend Perforated 6.9 7.0 6.8 6.7 8.0 8.0 <0.001 Non-perforated 2.7 2.9 2.9 3.0 3.9 4.2 <0.001 Values are weighted in-hospital mortality (%). p-trend from Cochran–Armitage test. Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Share and Cite MDPI and ACS Style Sultany, A.; Rao, A.; Gondal, A.; Theli, A.; Chikatimalla, R.; Omar, M.A.; Katamreddy, R.; Chakinala, R.C.; Sultany, M.S.; Dahiya, D.S.; et al. Outcomes and Predictors of Mortality in Perforated Versus Non-Perforated Peptic Ulcer Disease: A U.S. Nationwide Propensity-Matched Analysis, 2016–2021. J. Clin. Med. 2026, 15, 4358. https://doi.org/10.3390/jcm15114358 AMA Style Sultany A, Rao A, Gondal A, Theli A, Chikatimalla R, Omar MA, Katamreddy R, Chakinala RC, Sultany MS, Dahiya DS, et al. Outcomes and Predictors of Mortality in Perforated Versus Non-Perforated Peptic Ulcer Disease: A U.S. Nationwide Propensity-Matched Analysis, 2016–2021. Journal of Clinical Medicine. 2026; 15(11):4358. https://doi.org/10.3390/jcm15114358 Chicago/Turabian Style Sultany, Abdullah, Adishwar Rao, Amlish Gondal, Abhinay Theli, Rahul Chikatimalla, Mohamed A. Omar, Rewanth Katamreddy, Raja Chandra Chakinala, Mohammad Sulaiman Sultany, Dushyant Singh Dahiya, and et al. 2026. "Outcomes and Predictors of Mortality in Perforated Versus Non-Perforated Peptic Ulcer Disease: A U.S. Nationwide Propensity-Matched Analysis, 2016–2021" Journal of Clinical Medicine 15, no. 11: 4358. https://doi.org/10.3390/jcm15114358 APA Style Sultany, A., Rao, A., Gondal, A., Theli, A., Chikatimalla, R., Omar, M. A., Katamreddy, R., Chakinala, R. C., Sultany, M. S., Dahiya, D. S., Ghimire, S., & Georgetson, M. J. (2026). Outcomes and Predictors of Mortality in Perforated Versus Non-Perforated Peptic Ulcer Disease: A U.S. Nationwide Propensity-Matched Analysis, 2016–2021. Journal of Clinical Medicine, 15(11), 4358. https://doi.org/10.3390/jcm15114358 Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here. Article Metrics Article metric data becomes available approximately 24 hours after publication online.
