Non-communicable diseases like diabetes mellitus (DM), Hypertension (HTN) and chronic kidney disease (CKD) have emerged as significant health problems worldwide, with rising prevalence and high morbidity and mortality [1]. They are often associated with chronic diseases, and can be complicated by surgical disease, making it difficult to manage the perioperative period in a comprehensive and individualized way [2]. These diseases are associated with metabolic, vascular, and inflammatory changes that can affect disease manifestation, affect the time of diagnosis, increase the operative risk, and impact postoperative recovery [3].

The most common general surgical and urological diseases are cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia (BPH) and urolithiasis [4]. Although they have different pathophysiological mechanisms, they have a common presentation in adults and may necessitate elective or emergency surgery [5]. Chronic comorbidities might be associated with changing the clinical course of these disorders, either by changing the severity of the symptoms, or by increasing the risk of complications and/or influencing the choice of treatment [6]. DM has been associated with diminished immune response, slow healing and higher risk of developing postoperative infections [7,8]. During the perioperative period, HTN is a factor that complicates cardiovascular instability, and CKD plays a role in fluid and electrolyte management, drug metabolism and anesthetic care, all of which may make surgery more difficult [9,10].

Although surgical techniques, anaesthetic and peri-operative management have improved the outcomes for patients, people with multiple chronic diseases are still at increased risk of complications, extended hospital stay, admission to intensive care, re-hospitalization and death, compared to those without these multiple chronic diseases [11,12]. Therefore, careful preoperative evaluation, optimizing chronically-ill medical conditions and managing them by a multidisciplinary approach have become a necessary part of modern surgical practice. Nevertheless, clinical presentation, surgical strategy and outcomes are different in patients having different metabolic and cardiovascular comorbidities. In addition, there is limited data available to compare the overall effect of DM, HTN, and CKD in various common surgical diseases, especially in low-resource healthcare environments where the burden of chronic disease is still increasing.

Although chronic metabolic and CV diseases are becoming common in the society, there is scarcity of multi-center evidence on the impact of these two diseases on presentation, peri-operative management and outcome of common general surgical and urological diseases, especially in Pakistan. The study of these associations might yield evidence for better perioperative risk assessment and surgical decision making for patients with multiple comorbidities.

Research Objective

To evaluate the association of diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD) with the clinical presentation, surgical management, and postoperative outcomes of adult patients undergoing surgery for common general surgical and urological conditions, including cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia, and urolithiasis.

Study Design This study was designed as a prospective, multicenter observational cohort study to evaluate the association of diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD) with the clinical presentation, surgical management, and postoperative outcomes of adult patients undergoing surgery for common general surgical and urological conditions, including cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia (BPH), and urolithiasis (UL). These five conditions were selected a priori because they represent the most common benign surgical and urological diseases managed at the participating tertiary care hospitals and collectively account for a substantial proportion of elective and emergency surgical admissions. A prospective observational design was selected because the study aimed to investigate the natural relationship between pre-existing chronic comorbidities and surgical outcomes without influencing routine clinical management or allocating patients to any intervention. Patients were managed according to the standard institutional protocols and the treating surgeon's clinical judgment, ensuring that the study reflected routine clinical practice. Eligible patients were categorized according to the presence or absence of physician-confirmed DM, HTN, and CKD. Because these chronic diseases frequently coexist, their independent associations with surgical outcomes were evaluated after adjustment for potential confounding variables using multivariable statistical models. In addition, disease-specific subgroup analyses were planned to account for the clinical heterogeneity among the five surgical conditions and to improve the validity and interpretability of the findings. Study Setting The study was conducted at West China School Of Medicine, Sichuan University, China; Abbottabad Medical Complex, Abbottabad, Pakistan; District Headquarters (DHQ) Hospital, Abbottabad, Pakistan; Rehman Medical Institute (RMI), Peshawar, Pakistan; Mufti Mehmood Memorial Teaching Hospital, Dera Ismail Khan, Pakistan; Benazir Bhutto Hospital, Rawalpindi, Pakistan, affiliated with Rawalpindi Medical University (RMU); and Lady Reading Hospital, Peshawar, Pakistan, affiliated with Khyber Medical University (KMU). These hospitals are high-volume referral centers that provide comprehensive emergency and elective general surgical and urological services to patients. The multicenter design was adopted to increase the diversity and representativeness of the study population, enhance the external validity and generalizability of the findings, and reduce the potential influence of institution-specific clinical practices. Standardized patient recruitment procedures, data collection protocols, and outcome assessment methods were implemented across all participating centers to ensure methodological consistency. The participating hospital was recorded for each enrolled patient and considered during the statistical analysis to minimize potential center-related confounding. Study Duration The study was conducted over an 18-month recruitment period from January 2025 to June 2026. During this period, all eligible consecutive patients presenting to the participating departments were screened for eligibility and recruited after written informed consent. Each participant was prospectively followed from hospital admission until discharge and subsequently for 30 days after surgery to evaluate early postoperative outcomes. The 30-day follow-up period was selected because it is the internationally accepted timeframe for reporting postoperative morbidity and mortality following general surgical and urological procedures. Follow-up information was obtained through scheduled outpatient visits and review of hospital medical records. For patients unable to attend follow-up appointments, postoperative information was obtained through structured telephone interviews whenever appropriate to minimize loss to follow-up. Study Population The study population consisted of adult patients (≥18 years) diagnosed with cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia, or urolithiasis who underwent elective or emergency surgical treatment at either participating hospital during the study period. The diagnosis of each surgical condition was established by consultant surgeons or consultant urologists using standard clinical assessment, laboratory investigations, and disease-specific imaging modalities according to institutional protocols. Diagnostic investigations included ultrasonography, computed tomography (CT), plain radiography, uroflowmetry, prostate ultrasonography, renal function tests, and other relevant investigations depending on the patient's presenting condition. Because these five diseases differ in their clinical characteristics and surgical management, disease-specific variables (such as stone characteristics, appendiceal perforation, prostate size, and hernia characteristics) were also recorded whenever applicable. These variables were considered during subgroup analyses to reduce disease-related confounding. Sample Size The sample size was determined based on the primary study outcome, namely the occurrence of postoperative complications within 30 days after surgery. Since the primary analysis involved multivariable logistic regression to evaluate the association of DM, HTN, and CKD with postoperative complications while adjusting for potential confounding variables, the sample size was estimated using the events-per-variable (EPV) approach recommended for logistic regression models. Previous evidence indicates that postoperative complications occur in approximately 20% of patients undergoing surgery, depending on the type of surgical procedure and patient-related risk factors [13]. Assuming an expected postoperative complication rate of 20% (p = 0.20) and including 12 clinically relevant predictor variables in the final multivariable logistic regression model (DM, HTN, CKD, age, sex, body mass index, smoking status, ASA physical status, surgical disease category, urgency of surgery, operative approach, and participating hospital), a minimum of 10 outcome events per predictor variable was considered necessary to obtain stable and reliable regression estimates. Accordingly, the required sample size was calculated using the EPV formula: N=10k/p Where N = required sample size, k = number of predictor variables and p = expected proportion of postoperative complications. N=600 Therefore, a minimum sample size of 600 patients was required to ensure adequate statistical power for multivariable analyses while allowing adjustment for potential confounding variables and disease-specific subgroup analyses. Consecutive recruitment was continued until the target sample size was achieved. Sampling Technique A consecutive non-probability sampling technique was employed. All eligible patients presenting during the study period were screened consecutively for eligibility, and those fulfilling the inclusion criteria were invited to participate until the predetermined sample size was achieved. Consecutive sampling was selected to reduce selection bias by minimizing investigator discretion during patient recruitment and to reflect the routine clinical case mix encountered at the participating institutions. The number of patients screened, excluded, enrolled, and completing follow-up was documented to ensure transparency of participant recruitment and is presented in a STROBE participant flow diagram (Figure 1). Figure 1: Strobe flow diagram of patient recruitment, follow up and final analysis Inclusion and Exclusion Criteria The study population consisted of 18 years or older patients with definite diagnosis of cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia or urolithiasis who received elective or emergency surgery with written informed consent for the study. Patients under 18 years of age, pregnant women, patients who were managed non-surgically, patients with incomplete clinical records, patients with missing postoperative outcome data and patients who refused to participate were excluded from the study. Operational Definitions Diabetes Mellitus (DM): Patients were classified as having diabetes mellitus if they had a documented physician diagnosis, were receiving antidiabetic medication (oral hypoglycemic agents and/or insulin), or fulfilled the American Diabetes Association (ADA) diagnostic criteria, including fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), HbA1c ≥6.5%, 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test, or random plasma glucose ≥200 mg/dL in the presence of classic symptoms of hyperglycemia [14]. Hypertension (HTN): Hypertension was defined as a documented physician diagnosis, current use of antihypertensive medication, or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg measured on admission in accordance with the European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines [15]. Chronic Kidney Disease (CKD): Chronic kidney disease was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as evidence of kidney damage or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² persisting for at least three months, irrespective of the underlying cause [16]. Complicated Disease Presentation: Complicated disease presentation referred to advanced disease requiring urgent surgical management, including perforated or gangrenous appendicitis, acute cholecystitis with empyema or gangrene, incarcerated or strangulated inguinal hernia, complicated benign prostatic hyperplasia with urinary retention or recurrent urinary tract infection, and obstructive or infected urolithiasis, as confirmed by clinical, laboratory, imaging, and intraoperative findings. Emergency Surgery: Emergency surgery was defined as a surgical procedure performed during the same hospital admission because delaying surgery would have increased the risk of morbidity or mortality. Prolonged Operative Duration: Prolonged operative duration was defined as a total operative time exceeding 120 minutes, measured from skin incision to skin closure or completion of the endoscopic procedure. Increased Intraoperative Blood Loss: Increased blood loss was defined as estimated intraoperative blood loss greater than 300 mL or blood loss considered clinically significant by the operating surgeon requiring additional hemostatic intervention. Blood Transfusion: Blood transfusion was defined as the administration of one or more units of packed red blood cells during the intraoperative period or postoperative hospital stay. Conversion to Open Surgery: Conversion to open surgery referred to an unplanned change from a minimally invasive (laparoscopic or endoscopic) procedure to an open surgical approach because of technical difficulty, bleeding, adhesions, or intraoperative complications. Postoperative Surgical Site Infection (SSI): Surgical site infection was defined according to the Centers for Disease Control and Prevention (CDC) criteria as an infection occurring within 30 days after surgery involving the incision or operative site with clinical evidence of purulent drainage, positive microbiological culture, localized signs of infection, or diagnosis by the treating surgeon. Acute Kidney Injury (AKI): Acute kidney injury was defined according to the KDIGO AKI criteria as an increase in serum creatinine by ≥0.3 mg/dL within 48 hours, an increase to ≥1.5 times the baseline value within seven days, or urine output <0.5 mL/kg/hour for at least six hours [17]. Postoperative Complications: Postoperative complications included any adverse event occurring during hospitalization or within 30 days after surgery and were graded according to the Clavien–Dindo classification [18]. Intensive Care Unit (ICU) Admission: ICU admission was defined as transfer to the intensive care unit after surgery for advanced postoperative monitoring or organ-supportive therapy. Length of Hospital Stay: Length of hospital stay was defined as the number of days from the date of surgery until hospital discharge. Readmission: Readmission was defined as any unplanned hospital admission related to the index surgical procedure occurring within 30 days after discharge. Reoperation: Reoperation was defined as any unplanned return to the operating room during the same admission or within 30 days after surgery because of postoperative complications. Mortality: Mortality was defined as any all-cause death occurring during hospitalization or within 30 days following the index surgical procedure. Body Mass Index (BMI): Body mass index was calculated as weight (kg) divided by height squared (m²). Obesity was defined as BMI ≥30 kg/m². Smoking History: Smoking history was defined as current or former use of tobacco products, whereas individuals who had never smoked were classified as non-smokers. Questionnaire Development and Validation A structured data collection questionnaire was developed based on a comprehensive review of previously published surgical outcome studies, relevant clinical guidelines, and standardized definitions from international organizations, including the ADA, KDIGO, CDC, and Clavien–Dindo classification system. The questionnaire was designed to capture demographic characteristics, chronic comorbidities, clinical presentation, laboratory and imaging findings, perioperative variables, surgical management details, and 30-day postoperative outcomes. The initial draft was reviewed by experts in general surgery, urology, and internal medicine to ensure clinical relevance and content validity. A pilot assessment was conducted among a small group of eligible patients to evaluate clarity, completeness, and feasibility of data collection. Necessary modifications were incorporated before initiation of the final study data collection process. Pilot Testing Before the commencement of the main study, pilot testing of the data collection questionnaire was performed on a small sample of patients who fulfilled the study eligibility criteria. The pilot phase was conducted to assess the clarity of questions, feasibility of data collection procedures, completeness of required variables, and identification of any potential difficulties during patient recruitment and follow-up. Feedback obtained from the pilot assessment was reviewed by the research team, and necessary modifications were made to improve the accuracy, consistency, and practicality of the final data collection tool. Patients included in the pilot testing were not included in the final study analysis. Data Collection Procedure Patients were enrolled after confirmation of their diagnosis in the Departments of General Surgery and Urology at the participating tertiary care teaching hospitals. Eligible patients from both participating hospitals were consecutively recruited after providing written informed consent. Demographic data such as age, sex, BMI, smoking status and medical history were obtained after written informed consent, on a standardized data collection form. DM was determined by a documented physician diagnosis, current treatment, or established diagnostic criteria as per the American Diabetes Association (ADA), the European Society of Cardiology/European Society of HTN (ESC/ESH), and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, respectively [14-16]. Medical records, drug history, and pertinent lab information was checked to confirm the presence of these comorbidities. Details of the clinical presentation such as nature and duration of symptoms, pain, fever, nausea/vomiting, urinary symptoms, lower urinary tract symptoms in the patient with a diagnosis of benign prostatic hyperplasia, physical examination findings, laboratory investigations, and radiological imaging results were documented on a standardized data collection form prior to surgery. Surgical management data consisted of the urgency of surgery, elective or emergency; surgery type, surgical procedure; operative approach, open surgery or minimally invasive surgery; surgery duration, the duration of the surgery; intraoperative findings, findings during surgery; estimated blood loss, amount of blood lost from the body during surgery; blood transfusion, whether or not the patient received blood during surgery; intraoperative complications, any complications encountered during surgery. Where appropriate, procedure specific information was also provided including laparoscopic cholecystectomy, open cholecystectomy, laparoscopic appendectomy, open appendectomy, inguinal hernia — mesh, inguinal hernia — tissue repair, transurethral resection of the prostate, open prostatectomy for benign prostatic hyperplasia, ureteroscopy, percutaneous nephrolithotomy, extracorporeal shock wave lithotripsy, or open surgery of the urinary tract for urolithiasis. Patients were then followed throughout the hospital stay, and postoperative complications such as surgical site infection, wound complications, UTI, postoperative bleeding, cardiopulmonary complications, acute kidney injury, admission to intensive care unit, reoperation, hospital stay, readmission and in-hospital mortality were recorded from standardized hospital records and clinical assessment. Patients were followed for up to 30 days’ post surgery with outpatient follow-up visits or hospital records for delayed postoperative complications, readmission and mortality wherever possible. Bias Control Several strategies were implemented to minimize potential sources of bias. Consecutive recruitment of eligible patients was used to reduce selection bias and ensure a representative clinical sample. Standardized data collection forms and predefined operational definitions were used to minimize information bias and improve consistency across participating centers. Potential confounding factors, including age, sex, BMI, smoking status, type of surgical condition, urgency of surgery, and chronic comorbidities, were considered during multivariable logistic regression analysis to reduce the effect of confounding bias. Quality Assurance Quality assurance measures were maintained throughout the study to ensure accuracy and reliability of collected data. All investigators involved in patient recruitment and data collection were trained regarding study procedures, eligibility criteria, variable definitions, and outcome assessment. Regular review of completed data collection forms was performed to identify missing or inconsistent information. Standardized protocols for clinical assessment, laboratory evaluation, surgical data recording, and postoperative follow-up were applied across all participating hospitals to maintain methodological consistency. Data Management Collected data were entered into a secure electronic database using unique study identification numbers to maintain patient confidentiality. Data were checked for completeness, accuracy, and internal consistency before statistical analysis. Any discrepancies identified during data verification were resolved by reviewing original medical records. Access to the study database was restricted to authorized research team members, and all data were anonymized before analysis. Study Variables DM, HTN, CKD, age, sex, BMI, smoking history and other possible comorbidities were used as independent variables. Clinical presentation, operative findings, surgical procedure, operative time, postoperative complications, hospital stay, readmission, and in-hospital death rates were the dependent variables. Outcome Measures The main outcome measure was that the relationship between DM, HTN, and CKD to the complications that occurred after surgery for correction. Secondary outcome measures were differences in clinical presentation, operative findings, operative approach, operative time, time in hospital, intensive care unit (ICU) admission, readmission, and in-hospital mortality between the groups with and without these chronic comorbidities. Statistical Analysis IBM SPSS Statistics version 27.0 was used to enter, code and analyse data. Variables were presented as means ± standard deviation or as medians and interquartile ranges, depending on the distribution of the data, and as frequencies and percentages for categorical variables. Independent t-test and Chi-square test were used, depending on the type of data, to compare between groups. Multivariable logistic regression analysis was conducted to determine independent factors associated with postoperative complications and adverse clinical outcomes after adjusting for potential confounding factors, such as age, sex, body mass index, smoking status, type of surgical condition, urgency of surgery, and DM, HTN, and CKD. Odds ratios with 95% confidence intervals were computed and p-values < 0.05 (two-tailed) were deemed significant. Overall study design, participant recruitment, data collection, surgical management, follow-up, and outcome assessment. Adult patients undergoing surgery for cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia, or urolithiasis were prospectively recruited from two tertiary care hospitals and followed for 30 days after surgery to evaluate the association of diabetes mellitus, hypertension, and chronic kidney disease with postoperative outcomes. Figure 2: Overview of Methodology Ethical Considerations The study was conducted after obtaining ethical approval from the relevant Institutional Ethical Committees and administrative permission from the Heads of the participating departments at all study centers before commencement of data collection. Written informed consent was obtained from all participants before enrollment. Patient confidentiality was maintained by assigning unique study identification numbers and anonymizing all collected information. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and applicable local institutional research guidelines.

Of the 600 patients, 330 (55.00%) had at least one chronic comorbidity and 270 (45.00%) had none (table 1). Patients with chronic comorbidities were significantly older (63.43±11.82 vs. 48.72±12.51 years, p<0.001), had higher BMI (29.13±5.25 vs. 26.44±4.12 kg/m², p<0.001), and more frequently had a smoking history (102, 30.91% vs. 54, 20.00%; p=0.004). Among patients with comorbidities, DM was present in 214 (64.85%), HTN in 278 (84.24%), CKD in 96 (29.09%), and two or more chronic diseases in 174 (52.73%).

Table 1. Baseline Demographic and Clinical Characteristics of Patients According to Chronic Disease Status (N=600)

* Significant p <0.05

Among the 214 diabetic patients, 122 (57.01%) had diabetes for ≥5 years, while 128 (59.81%) had HbA1c ≥7%, shown in table 2. Of the 278 hypertensive patients, 132 (47.48%) had uncontrolled HTN and 118 (42.45%) required two or more antihypertensive medications. Among 96 CKD patients, Stage 3 CKD was the most common (42, 43.75%), whereas only 6 (6.25%) were dialysis dependent.

Table 2. Characteristics of Diabetes Mellitus, Hypertension, and Chronic Kidney Disease

Patients with chronic comorbidities more frequently presented after 48 hours (124, 37.58% vs. 62, 22.96%), had severe pain (152, 46.06% vs. 88, 32.59%), complicated presentation (104, 31.52% vs. 46, 17.04%), elevated CRP (154, 46.67% vs. 84, 31.11%), CT-confirmed complicated disease (86, 26.06% vs. 38, 14.07%), emergency surgery (138, 41.82% vs. 82, 30.37%), prolonged operative duration (96, 29.09% vs. 42, 15.56%), and blood transfusion (62, 18.79% vs. 22, 8.15%) (all p<0.05), shown in table 3. Benign prostatic hyperplasia was more common among patients with comorbidities (84, 25.45% vs. 32, 11.85%; p<0.001), whereas acute appendicitis was more frequent in patients without comorbidities (74, 27.41% vs. 52, 15.76%; p=0.002).

Table 3. Comprehensive Comparison of Surgical Conditions, Clinical Presentation, Preoperative Findings, and Surgical Management According to Chronic Disease Status (N=600)

LUTS = lower urinary tract symptoms; BPH = benign prostatic hyperplasia; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate; PCNL = percutaneous nephrolithotomy; ESWL = extracorporeal shock wave lithotripsy. Percentages were calculated using the respective chronic disease status group denominator.

According to table 4, patients with chronic comorbidities experienced significantly higher rates of difficult dissection (86, 26.06% vs. 36, 13.33%), intraoperative complications (52, 15.76% vs. 18, 6.67%), surgical site infection (58, 17.58% vs. 18, 6.67%), acute kidney injury (62, 18.79% vs. 8, 2.96%), ICU admission (46, 13.94% vs. 10, 3.70%), prolonged hospital stay (112, 33.94% vs. 38, 14.07%), 30-day readmission (48, 14.55% vs. 12, 4.44%), in-hospital mortality (22, 6.67% vs. 4, 1.48%), and overall postoperative complications (156, 47.27% vs. 54, 20.00%) (all p<0.05).

Table 4. Operative Findings, Postoperative Complications, and Clinical Outcomes According to Chronic Disease Status (N=600)

Multivariable logistic regression demonstrated that CKD (AOR=3.14, 95% CI: 1.89–5.22, p<0.001), multiple chronic comorbidities (AOR=2.71, p<0.001), emergency surgery (AOR=2.06, p<0.001), DM (AOR=1.82, p=0.004), operative duration >120 minutes (AOR=1.67, p=0.010), HTN (AOR=1.56, p=0.018), and BMI ≥30 kg/m² (AOR=1.42, p=0.043) were independent predictors of postoperative complications (table 5).

Table 5. Multivariable Logistic Regression Analysis of Independent Predictors of Postoperative Complications among Surgical Patients (N=600)

Among patients with DM, postoperative complications occurred in 112 of 214 patients (52.34%), shown in table 6. Similarly, complications developed in 132 of 278 hypertensive patients (47.48%) and in 68 of 96 patients with CKD (70.83%). All three chronic conditions showed significant associations with postoperative complications (p<0.001).

Table 6. Association of Individual Chronic Comorbidities with Overall Postoperative Complications among Patients with DM, Hypertension, or CKD

The frequency of adverse postoperative outcomes increased progressively with the number of chronic comorbidities (table 7). Overall postoperative complications increased from 54 of 270 patients (20.00%) with no chronic disease to 50 of 156 (32.05%) with one comorbidity, 75 of 132 (56.82%) with two comorbidities, and 31 of 42 (73.81%) with all three comorbidities. Similarly, ICU admission increased from 10 (3.70%) to 8 (5.13%), 25 (18.94%), and 13 (30.95%); prolonged hospital stay from 38 (14.07%) to 25 (16.03%), 55 (41.67%), and 32 (76.19%); 30-day readmission from 12 (4.44%) to 8 (5.13%), 25 (18.94%), and 15 (35.71%); and in-hospital mortality from 4 (1.48%) to 4 (2.56%), 10 (7.58%), and 8 (19.05%), respectively (trend p<0.001).

Table 7. Effect of Increasing Number of Chronic Comorbidities on Postoperative Outcomes (N=600)

Statistical analysis: Chi-square test for trend demonstrated a significant association between increasing chronic disease burden and higher risk of postoperative adverse outcomes (χ² trend = 46.28, p <0.001).

Of the 600 patients, 330 (55.00%) had at least one chronic comorbidity and 270 (45.00%) had none (table 1). Patients with chronic comorbidities were significantly older (63.43±11.82 vs. 48.72±12.51 years, p<0.001), had higher BMI (29.13±5.25 vs. 26.44±4.12 kg/m², p<0.001), and more frequently had a smoking history (102, 30.91% vs. 54, 20.00%; p=0.004). Among patients with comorbidities, DM was present in 214 (64.85%), HTN in 278 (84.24%), CKD in 96 (29.09%), and two or more chronic diseases in 174 (52.73%).

Table 1. Baseline Demographic and Clinical Characteristics of Patients According to Chronic Disease Status (N=600)

* Significant p <0.05

Among the 214 diabetic patients, 122 (57.01%) had diabetes for ≥5 years, while 128 (59.81%) had HbA1c ≥7%, shown in table 2. Of the 278 hypertensive patients, 132 (47.48%) had uncontrolled HTN and 118 (42.45%) required two or more antihypertensive medications. Among 96 CKD patients, Stage 3 CKD was the most common (42, 43.75%), whereas only 6 (6.25%) were dialysis dependent.

Table 2. Characteristics of Diabetes Mellitus, Hypertension, and Chronic Kidney Disease

Patients with chronic comorbidities more frequently presented after 48 hours (124, 37.58% vs. 62, 22.96%), had severe pain (152, 46.06% vs. 88, 32.59%), complicated presentation (104, 31.52% vs. 46, 17.04%), elevated CRP (154, 46.67% vs. 84, 31.11%), CT-confirmed complicated disease (86, 26.06% vs. 38, 14.07%), emergency surgery (138, 41.82% vs. 82, 30.37%), prolonged operative duration (96, 29.09% vs. 42, 15.56%), and blood transfusion (62, 18.79% vs. 22, 8.15%) (all p<0.05), shown in table 3. Benign prostatic hyperplasia was more common among patients with comorbidities (84, 25.45% vs. 32, 11.85%; p<0.001), whereas acute appendicitis was more frequent in patients without comorbidities (74, 27.41% vs. 52, 15.76%; p=0.002).

Table 3. Comprehensive Comparison of Surgical Conditions, Clinical Presentation, Preoperative Findings, and Surgical Management According to Chronic Disease Status (N=600)

LUTS = lower urinary tract symptoms; BPH = benign prostatic hyperplasia; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate; PCNL = percutaneous nephrolithotomy; ESWL = extracorporeal shock wave lithotripsy. Percentages were calculated using the respective chronic disease status group denominator.

According to table 4, patients with chronic comorbidities experienced significantly higher rates of difficult dissection (86, 26.06% vs. 36, 13.33%), intraoperative complications (52, 15.76% vs. 18, 6.67%), surgical site infection (58, 17.58% vs. 18, 6.67%), acute kidney injury (62, 18.79% vs. 8, 2.96%), ICU admission (46, 13.94% vs. 10, 3.70%), prolonged hospital stay (112, 33.94% vs. 38, 14.07%), 30-day readmission (48, 14.55% vs. 12, 4.44%), in-hospital mortality (22, 6.67% vs. 4, 1.48%), and overall postoperative complications (156, 47.27% vs. 54, 20.00%) (all p<0.05).

Table 4. Operative Findings, Postoperative Complications, and Clinical Outcomes According to Chronic Disease Status (N=600)

Multivariable logistic regression demonstrated that CKD (AOR=3.14, 95% CI: 1.89–5.22, p<0.001), multiple chronic comorbidities (AOR=2.71, p<0.001), emergency surgery (AOR=2.06, p<0.001), DM (AOR=1.82, p=0.004), operative duration >120 minutes (AOR=1.67, p=0.010), HTN (AOR=1.56, p=0.018), and BMI ≥30 kg/m² (AOR=1.42, p=0.043) were independent predictors of postoperative complications (table 5).

Table 5. Multivariable Logistic Regression Analysis of Independent Predictors of Postoperative Complications among Surgical Patients (N=600)

Among patients with DM, postoperative complications occurred in 112 of 214 patients (52.34%), shown in table 6. Similarly, complications developed in 132 of 278 hypertensive patients (47.48%) and in 68 of 96 patients with CKD (70.83%). All three chronic conditions showed significant associations with postoperative complications (p<0.001).

Table 6. Association of Individual Chronic Comorbidities with Overall Postoperative Complications among Patients with DM, Hypertension, or CKD

The frequency of adverse postoperative outcomes increased progressively with the number of chronic comorbidities (table 7). Overall postoperative complications increased from 54 of 270 patients (20.00%) with no chronic disease to 50 of 156 (32.05%) with one comorbidity, 75 of 132 (56.82%) with two comorbidities, and 31 of 42 (73.81%) with all three comorbidities. Similarly, ICU admission increased from 10 (3.70%) to 8 (5.13%), 25 (18.94%), and 13 (30.95%); prolonged hospital stay from 38 (14.07%) to 25 (16.03%), 55 (41.67%), and 32 (76.19%); 30-day readmission from 12 (4.44%) to 8 (5.13%), 25 (18.94%), and 15 (35.71%); and in-hospital mortality from 4 (1.48%) to 4 (2.56%), 10 (7.58%), and 8 (19.05%), respectively (trend p<0.001).

Table 7. Effect of Increasing Number of Chronic Comorbidities on Postoperative Outcomes (N=600)

Statistical analysis: Chi-square test for trend demonstrated a significant association between increasing chronic disease burden and higher risk of postoperative adverse outcomes (χ² trend = 46.28, p <0.001).

In the present multicenter prospective study, DM, HTN and CKD had significant effect on the clinical presentation, surgical management and postoperative outcomes of patients undergoing surgery for cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia and urolithiasis. Patients with chronic comorbidities were significantly older (63.43±11.82 vs. 48.72±12.51 years, p<0.001), had higher BMI (29.13±5.25 vs. 26.44±4.12 kg/m², p<0.001), and higher smoking prevalence (30.91% vs. 20.00%, p=0.004). Additionally, HTN was the most common comorbidities (84.24%), followed by DM (64.85%) and CKD (29.09%) among patients with comorbidities. This finding is consistent with previous evidence of a growing prevalence of chronic metabolic diseases in surgical populations and their association with inflammatory, vascular and metabolic abnormalities that increase the complexity of surgery. Earlier research comparing surgical outcomes has also found that individuals with diabetes and chronic medical conditions are a surgical population at higher risk that needs to be managed optimally during the perioperative period [19]. The present work showed that delayed and greater clinical severity was related to chronic comorbidities. Patients with DM/HTN/CKD more frequently presented after 48 hours (37.58% vs. 22.96%, p<0.001), severe pain (46.06% vs. 32.59%, p=0.001), complicated disease presentation (31.52% vs. 17.04%, p<0.001), elevated CRP (46.67% vs. 31.11%, p<0.001), and CT-confirmed complicated disease (26.06% vs. 14.07%, p<0.001). Impaired immune response, altered inflammatory pathway and delayed recognition of the acute symptoms in patients with chronic diseases may explain this observation. Previous studies have shown that diabetes has been linked to impaired host defence mechanisms and higher inflammatory complications leading to more severe presentations of infection-related and surgical diabetes. This relationship has been consistently found in several large systematic reviews; diabetes was found to be associated with postoperative complications in various non-cardiac surgeries [20]. In the current series, chronic comorbidities were also found to heavily affect surgical planning and complexity. Patients with DM/HTN/CKD had higher rates of emergency surgery (41.82% vs. 30.37%, p=0.006), open surgical procedures (38.18% vs. 27.41%), prolonged operative duration >120 minutes (29.09% vs. 15.56%, p<0.001), increased blood loss (26.67% vs. 13.33%, p<0.001), blood transfusion requirement (18.79% vs. 8.15%, p<0.001), and conversion to open surgery (11.52% vs. 4.44%, p=0.004). These results indicate that chronic disease may be associated with more difficult interventions because of expression of the disease and decrease in physiological reserves. In surgical cohorts, there were similar findings that diabetes and cardiovascular comorbidities were linked to higher operative difficulty, longer procedure and higher utilization of resources. In addition, the kidney-diseased population is especially susceptible because the renal function is impaired in these patients, which compromises their ability to regulate fluid, tolerate perioperative stress, and clear medications [21]. The complications in postoperative outcomes were significantly higher in patients with chronic diseases. In patients with DM/HTN/CKD, the overall postoperative complications were significantly higher (47.27%) than in patients without DM/HTN/CKD (20.00%) (p<0.001). Specific complications were significantly higher among comorbid patients, including surgical site infection (17.58% vs. 6.67%), wound complications (15.76% vs. 5.19%), cardiopulmonary events (19.39% vs. 5.19%), acute kidney injury (18.79% vs. 2.96%), ICU admission (13.94% vs. 3.70%), prolonged hospitalization (33.94% vs. 14.07%), and in-hospital mortality (6.67% vs. 1.48%). The results are similar to those of previous meta-analyses, which demonstrated that diabetes itself is associated with increased infection rates and wound-related complications after surgery, and that CKD is strongly linked to postoperative infectious complications and mortality. A multi-center cohort study found that CKD patients had significantly increased adjusted risks of postoperative mortality and complications, which was similar to the results in the present study [22]. Univariate and multivariate logistic regression showed that adverse surgical outcomes were independent of other variables, including chronic diseases. CKD showed the strongest association with postoperative complications (AOR=3.14, 95% CI: 1.89–5.22, p<0.001), followed by multiple chronic comorbidities (AOR=2.71, p<0.001), emergency surgery (AOR=2.06, p<0.001), DM (AOR=1.82, p=0.004), operative duration >120 minutes (AOR=1.67, p=0.010), and HTN (AOR=1.56, p=0.018). Furthermore, there appeared to be a clear dose-response relationship: the proportion of patients with postoperative complications was 20.00% with no chronic disease, 32.05% with one chronic disease, 56.82% with two chronic diseases, and 73.81% of patients with DM+HTN+CKD (p<0.001). The results of this study highlight the importance of the burden of disease and not just one disease alone when calculating surgical risk. In parallel, there is evidence that multimorbidity significantly contributes to higher rates of postoperative complications, hospital resource utilization and mortality [23,24]. This study underscores the need for a holistic assessment and optimization of the patients with DM, HTN and CKD prior to surgery. Optimizing glycemic and blood pressure control, optimizing renal function and undertaking individual perioperative planning may decrease postoperative morbidity in high-risk patients. This study's strengths lie in the analysis of a number of common surgical and urological disorders in a large multi-center cohort, providing a mechanism to analyze the impact of overall chronic disease burden on surgical outcomes. Further studies with extended follow-up and disease-specific subgroups are recommended to provide more insights into long-term outcomes and to establish disease-specific risk prediction models for multimorbid patients. Strengths and Limitations This prospective multicenter observational study included 600 patients recruited from six high-volume tertiary care teaching hospitals: Abbottabad Medical Complex, Abbottabad; District Headquarters (DHQ) Hospital, Abbottabad; Rehman Medical Institute (RMI), Peshawar; Mufti Mehmood Memorial Teaching Hospital, Dera Ismail Khan; Benazir Bhutto Hospital, Rawalpindi, affiliated with Rawalpindi Medical University; and Lady Reading Hospital, Peshawar, affiliated with Khyber Medical University. The study provided a comprehensive evaluation of the association of diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD) with clinical presentation, surgical management, and postoperative outcomes among patients undergoing common general surgical and urological procedures, including cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia, and urolithiasis. The study incorporated detailed assessment of baseline characteristics, disease presentation, perioperative variables, postoperative complications, and 30-day clinical outcomes. Multivariable logistic regression analysis was performed to identify independent predictors of adverse postoperative outcomes after adjustment for potential confounding factors. Furthermore, evaluation of increasing chronic disease burden provided clinically relevant information regarding the relationship between multimorbidity and surgical outcomes. However, several limitations should be considered. As the study was conducted in tertiary care teaching hospitals, the findings may not be fully generalizable to primary and secondary healthcare settings. Due to the observational study design, causal relationships between chronic comorbidities and postoperative outcomes cannot be definitively established. Although important confounding variables were adjusted for in the multivariable analysis, residual confounding from unmeasured factors, including socioeconomic status, nutritional status, medication adherence, and long-term disease control, may have influenced the observed associations. Additionally, follow-up was limited to 30 days after surgery; therefore, long-term complications, functional outcomes, and quality-of-life measures could not be evaluated.

DM, HTN, and CKD have significant impact on the clinical presentation, surgical complexity, and postoperative outcomes in patients undergoing surgery for cholelithiasis, acute appendicitis, inguinal hernia, benign prostatic hyperplasia and urolithiasis, as evidenced in this multicenter prospective study. In the chronic co-morbid patients there was a delay in presentation, more complex disease patterns, higher number of emergency surgical procedures, higher operative difficulty, and significantly higher post-operative morbidity. The highest independent risk for adverse outcomes was CKD, and the risks of complications rose as the chronic disease burden increased, with patients having concurrent DM, HTN, and CKD having a risk of 73.81%. The results indicated that early recognition, thorough pre-operative optimization, multi-disciplinary management of the peri-operative period and personalised risk stratification are all important in the surgical management of patients with chronic medical conditions to achieve the best surgical outcomes.

APPENDICES

Table 8. Standardized data collection questionnaire used for recording demographic characteristics, clinical findings, operative details, postoperative outcomes, and follow-up information of study participants.