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\begin{document}

\title{The role of basic laboratory parameters in diagnosing acute appendicitis
and determining disease severity in the elderly}



\author[1]{Mustafa Yeni}%
\author[2]{Rıfat Peksöz}%
\affil[1]{Erzurum City Hospital}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 29, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: Abdominal pain constitutes the most common complaint for
geriatric patients who present to the emergency department, with nearly
20\% suffering from acute appendicitis (AA). Although key for diagnosis,
clinical symptoms tend to be weak and atypical in the elderly.
Therefore, patients present late to health institutions. Hence,
prognosis and complication rates are worse in the elderly. Here, we
aimed to reveal the role of basic laboratory parameters in diagnosing AA
and determining disease severity. Methods: 143 elderly patients who
underwent appendectomy were retrospectively analyzed. The patients were
divided into three groups based on AA severity as Group I: negative
appendectomy (n=15); Group IIa: uncomplicated appendicitis (n=79); Group
IIb: complicated appendicitis (n=49). Results: We found no difference
between the groups for age, sex, or comorbid diseases
(p\textgreater{}0.05). As the time of admission to the hospital
increases, the severity of the disease increases. Group IIb had higher
length of stay and complication rates (p\textless{}.0.05) Conclusions:
Preoperative WBC, neutrophil, NLR, MPV, CRP, and direct and total
bilirubin levels can be used as biomarkers to determine AA diagnosis in
the elderly. NLR, PLR, RDW, CRP, and direct and total bilirubin levels
can be used to determine the presence of complications in appendicitis.%
\end{abstract}%



\sloppy


\selectlanguage{english}
\begin{longtable}[]{@{}l@{}}
\toprule
\selectlanguage{polish}\vtop{\hbox{\strut \textbf{The role of basic laboratory parameters in
diagnosing acute appendicitis and determining disease severity in the
elderly} \textbf{Abstract} \textbf{Background:} Abdominal pain
constitutes the most common complaint for geriatric patients who present
to the emergency department, with nearly 20\% suffering from acute
appendicitis (AA). Although key for diagnosis, clinical symptoms tend to
be weak and atypical in the elderly. Therefore, patients present late to
health institutions. Hence, prognosis and complication rates are worse
in the elderly. Here, we aimed to reveal the role of basic laboratory
parameters in diagnosing AA and determining disease severity.
\textbf{Methods:} 143 elderly patients who underwent appendectomy were
retrospectively analyzed. The patients were divided into three groups
based on AA severity as Group I: negative appendectomy (n=15); Group
IIa: uncomplicated appendicitis (n=79); Group IIb: complicated
appendicitis (n=49). \textbf{Results:} We found no difference between
the groups for age, sex, or comorbid diseases (p\textgreater{}0.05). As
the time of admission to the hospital increases, the severity of the
disease increases. Group IIb had higher length of stay and complication
rates (p\textless{}.0.05) \textbf{Conclusions:} Preoperative WBC,
neutrophil, NLR, MPV, CRP, and direct and total bilirubin levels can be
used as biomarkers to determine AA diagnosis in the elderly. NLR, PLR,
RDW, CRP, and direct and total bilirubin levels can be used to determine
the presence of complications in appendicitis. \textbf{Key Words:
Geriatric patients, acute appendicitis, morbidity, laboratory
parameters} \textbf{WHAT'S KNOWN? (what is already known about this
subject?)} Acute appendicitis is the most common surgical disease
worldwide. Although known as a young person disease, it has an increased
incidence among geriatric patients with increased life expectancy. AA
constitutes 20\% of elderly patients presenting to the emergency room
with abdominal pain. Due to the obscurity of key clinical symptoms and
findings, difficult access to basic imaging methods like USG and CT, and
the low diagnostic values of these methods in elderly patients, basic
laboratory parameters are important for this patient group.
\textbf{WHAT'S NEW? (what does this study contribute to the
literature?)} WBC, neutrophil, NLR, MPV, CRP, and direct and total
bilirubin levels can be used in the diagnosis of AA in elderly patients.
NLR, PLR, RDW, CRP, and direct and total bilirubin levels can be used to
determine the complications in appendicitis. \textbf{1 INTRODUCTİON} One
of the most common causes of acute abdomen, acute appendicitis (AA) is
caused by inflammation of the appendix. It is the most common disease
that requires emergency abdominal surgery. The disease has an incidence
of about 7-10\% throughout life {[}1,2{]}. While known as a young person
disease, incidence of AA has been increasing in the elderly with
increased life expectancy {[}3{]}. Abdominal pain constitutes the most
common complaint for geriatric patients who present to the emergency
department, with nearly 20\% suffering from acute appendicitis. In
geriatric patients, emergency appendectomy is the third most common
reason for abdominal surgery {[}4,5{]}. AA diagnosis includes the use of
anamnesis, physical examination, laboratory tests, and radiologic
methods {[}6{]}. Classical appendicitis findings like right lower
abdominal pain and tenderness, leukocytosis, and fever are seen in only
26\% of elderly patients {[}2,7{]}. Thus, it is difficult to diagnose AA
in the elderly population. Geriatric patients undergo a number of
physiological changes in their bodies. For this patient group, clinical
symptoms and signs are also weaker and atypical. Patients tend to
present late to the emergency department, leading to delayed diagnosis
and treatment. Elderly patients have a worse prognosis and higher
complication rates compared to young patients {[}2,3,8{]}. Besides,
since elderly patients are likely to have more comorbid diseases,
morbidity and mortality rates are also increased. Hence, early diagnosis
and appropriate surgical intervention are vital for elderly patients
{[}8,9{]}. Due to the obscurity of symptoms and findings, not using
advanced imaging methods in the first place for diagnosis, and the
difficulty to access such devices particularly in rural regions, basic
laboratory tests gain even more importance. These tests are simple,
inexpensive, and easily accessible in almost all health institutions,
providing information on biomarkers with an acceptable diagnostic value
{[}10{]}. Although studies on this matter have increased recently, there
is limited research on the diagnostic efficiency of laboratory
parameters in geriatric acute appendicitis {[}1,9{]}. The aim here was
to analyze patients operated for the diagnosis of AA in light of the
literature and to reveal the predictive value of basic preoperative
laboratory parameters in diagnosing AA and determining disease severity.
\textbf{2 MATERIALS AND METHODS} Approval was obtained from the Ethics
Committee of Erzurum Regional Training and Research Hospital (No.
2020/13-146). 3,856 adult patients aged over 18 years were operated for
the diagnosis of acute appendicitis between January 2015 and August
2020. Data belonging to 160 patients (4.15\%) aged over 65 years were
retrospectively analyzed. 17 patients whose blood parameters were
affected by causes other than acute appendicitis were excluded (3
patients whose blood parameters could not be determined, 3 with
malignant pathology, 5 with multiple comorbid diseases, and 6 with other
surgical pathologies). 143 patients aged over 65 years were found to be
eligible for the research. Patients' sex, age, time from symptom onset
to admission, comorbidities, preoperative blood results, preoperative
images, type of anesthesia, type of surgery, length of hospital stay,
complication status, and histopathological results for appendectomy
materials were obtained from the hospital's digital records. The
patients were divided into three groups based on the results of their
appendix histopathology. Patients in group I (normal appendix, lymphoid
hyperplasia, obliterative appendix) were evaluated as normal. (Negative
appendectomy) Patients in group IIa (phlegmonous appendicitis, catarrhal
appendicitis, suppurative appendicitis) were evaluated as noncomplicated
appendicitis. Patients in group IIb (gangrenous appendicitis, perforated
appendicitis, plastron appendicitis) were evaluated as complicated
appendicitis. \textbf{2.1 Statistical Analysis} Descriptive data were
expressed as mean and standard deviation for the numerical variables and
as number and percentages for the categorical variables. The
distribution of the data was examined with histogram graphics. After
examining the homogenity of the data, analysis was performed with One
Way Anova, Kruskal Wallis tests. Tukey and Tamhane tests were used for
post hoc analysis. Chi- square test used for two categorical data
analysis. Receiver operating characteristic (ROC) curves were created to
measure the ability of laboratory values to distinguish of acute
appendicitis and complicated appendicitis status. The area under curve
(AUC) and cut-off value of each measurement were determined.
Specificity, Sensitivity and positive likely-hood ratio (LR+) cut-off
values were calculated and evaluated together. A p value of
\textless{}0.05 was considered statistically significant. Statistical
analysis was performed using SPSS version 23.0 software. \textbf{2.2
Receiver operating characteristic curve analysis (ROC)} ROC curves were
created to examine the differentiation of laboratory parameters for
pathology positivity. AUC and cut-off values of some parameters were
determined and their sensitivity, specificity, and LR+ cut-off points
were calculated. ROC analyses was carried out both for patients
diagnosed with acute appendicitis and those with normal appendix (Table
2, Figure. 1). Also, separate ROC analyses were performed for
complicated and uncomplicated patients (Table 3, Figure 2). \textbf{3
RESULTS} 143 patients aged over 65 years were examined over a period of
six years. Of the patients, 60 (41.95\%) were male and 83 (58.05\%) were
female, with a mean age of 69.69±6.34 years (range: 65-104 years).
69.9\% of the patients had a comorbid disease. The sample was divided
into three groups as Group I: negative appendectomy (n=15, 10.49\%);
Group IIa: uncomplicated appendicitis (n=79, 55.24\%); Group IIb:
complicated appendicitis (n=49, 34.27\%) (Table 1). There was no
significant difference between the groups in terms of age, sex, or
comorbid disease (p\textgreater{}0.05). Time from the onset of abdominal
pain to hospital admission was 1.67±1.04 days in group I, 1.59±0.65 days
in group IIa, and 3.33±1.28 days in group IIb, with a significant
difference between the groups (p\textless{}0.05) (Table 1). Regarding
advanced imaging methods, 77.6\% of the patients were examined by
ultrasonography (USG) and 69.9\% by abdominal computed tomography (CT).
CT was found to have a sensitivity of 77.7\% and a specificity of 70\%,
while USG was found to have a sensitivity of 74.2\% and a specificity of
18.2\% (Table 1). \textbf{Table 1. Demographic and clinical features of
the patients} \textbf{Table 1. Demographic and clinical features of the
patients} \textbf{Table 1. Demographic and clinical features of the
patients} \textbf{Table 1. Demographic and clinical features of the
patients} \textbf{Table 1. Demographic and clinical features of the
patients} \textbf{Table 1. Demographic and clinical features of the
patients} \textbf{Appendix Type} \textbf{Appendix Type} \textbf{Appendix
Type} P value Normal Appendix (n=15) Uncomplicated AA (n=79) Complicated
AA (n=49) Sex male 8 27 25 0,110 female}\hbox{\strut total
7}\hbox{\strut 15 52}\hbox{\strut 79 24}\hbox{\strut 49 Age Age
70.53±6.17 69,15±6,47 70,31±6,22 0,278 Comorbid disease present 9 58 33
0,518 apsent 6 21 16 Pre-hospital delay/ day Pre-hospital delay/ day
1.67±1.04 1.59±0.65 3.33±1.28 \textbf{\textless{}0,001*} Length of
stay/day Length of stay/day 3.13±2.56 3.34±2.01 6.59±5.93
\textbf{0,007*} Post.op complication present 3 24 24 \textbf{0,042}
apsent 12 55 25 \emph{Diagnostic
tools}}\hbox{\strut Ultrasonogrophy}\hbox{\strut Computed tomography
\emph{Diagnostic
tools}}\hbox{\strut Ultrasonogrophy}\hbox{\strut Computed tomography n
Sensitivity (\%) 74.2 77.7 Specificity
(\%)}\hbox{\strut 18.2}\hbox{\strut 70 --------}}\selectlanguage{ngerman}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

\textbf{*:} Group IIb was significantly higher than other groups (group
I, group IIa) in Post-hoc analysis

The patients were evaluated for total bilirubin, direct bilirubin, CRP
and 11 hemogram subparameters. Yet, only subparameters with a high
diagnostic value were discussed.

There were significant differences between the groups in terms of
neutrophil, NLR, CRP, TB, and DB levels (p\textless{}0.05).

WBC, neutrophil, NLR, MPV, total bilirubin, direct bilirubin, and CRP
levels were found as markers with high diagnostic value for diagnosing
acute appendicitis (Table 2, Figure 1).

\textbf{Table 2. The ROC analysis for normal appendix and acute
appendicitis}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Parameters\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Cutt-off value\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
AUC\\
(p)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Sensitivity\\
(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Specificity\\
(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
LR+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
CRP\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1,23\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,668\\
(0,143)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
77\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
57\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1,81\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
WBC\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
8,97\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,722\\
(0,052)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
85\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
57\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1,98\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Neutrophil\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
6,36\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,743\\
(0,033)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
86\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
71\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
3,02\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
NLR\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
3,28\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,700\\
(0,080)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
83\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
71\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
2,93\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
MPV\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
6,905\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,624\\
(0,277)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
88\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
42\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1,55\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Total Bilirubin\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,695\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,718\\
(0,057)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
61\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
85\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
4,32\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Direct Bilirubin\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,235\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,716\\
(0,061)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
65\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
85\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
4,58\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Abbreviations: CRP; C-reactive protein, WBC: White blood cell, NLR;
Neutrophil to lymphocyte ratio, MPV; Mean platelet volume\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

NLR, PLR, RDW, CRP, TB, and DB levels were found as markers with high
diagnostic value for differentiating between complicated and
uncomplicated appendicitis (Table 3, Figure 2).

\textbf{Table 3. The ROC analysis for complicated and uncomplicated
appendicitis}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Parameters\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Cutt-off value\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
AUC\\
(p)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Sensitivity\\
(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Specificity\\
(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
LR+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
CRP\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
5,11\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,833\\
(\textless{}0,000)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
72\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
76\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
3,00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
NLR\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
5,10\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,617\\
(0,065)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
72\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
44\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1,28\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
PLR\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
190,62\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,641\\
(0,027)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
50\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
82\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
2,77\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
RDW\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
13,15\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,634\\
(0,035)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
69\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
60\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1,73\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Total Bilirubin\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,87\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,621\\
(0,056)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
52\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
72\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1,88\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Direct Bilirubin\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,30\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
0,690\\
(0,003)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
58\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
78\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
2,65\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Abbreviations: CRP; C-reactive protein, NLR; Neutrophil to lymphocyte
ratio, PLR: platelet to lymphocyte ratio, RDW; red cell distribution
width

\textbf{Figure 2: ROC analysis for uncomplicated and complicated
appendicitis}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Of the patients, 2.8\% were operated under spinal anesthesia and 97.2\%
under general anesthesia. 102 of the operations (71.3\%) were open
(48.3\% Mc Burney, 17.5\% paramedian, 5.6\% midline) and 42 (28.7\%)
were laparoscopic.

Length of hospital stay was 3.13\selectlanguage{ngerman}±2.56 days in group I, 3.34±2.01 days in
group IIa, and 6.59±5.93 days in group IIb, with a significant
difference between the groups (p\textless{}0.05) (Table1).

Postoperative complication rate was 35.6\%. Complication rates in the
groups were 2.09\% in group I, 16.7\% in group IIa, and 16.7\% in group
IIb, with significant differences (p\textless{}0.05) (Table 1). No
mortality was observed.

\textbf{4 DISCUSSION}

In elderly individuals, rebound sensitivity decreases due to atrophy of
the abdominal muscles, along with increased pain threshold due to
conduction differences in the nervous system and certain changes in the
detection and limitation of pain. Hence, the clinical picture tends to
be atypical and obscure in the elderly {[}11{]}. The time from the onset
of symptoms to hospital admission and surgery also seems higher in the
elderly {[}12,13{]}. Delayed admission leads to perforation of the
appendix. Acute appendicitis perforation is observed in 18-34\% of the
general population {[}6{]}. However, this rate increases up to 41-56.3\%
in geriatric patients {[}2,3,9{]}. Male sex, anorexia, fever
\selectlanguage{english}[?]38\selectlanguage{english}\textsuperscript{[?]}C, and duration of pain before admission are risk
factors for perforated appendicitis. The most important factor remains
delayed admission to hospital {[}3,6{]}. Male patients are observed to
be more reluctant for admission to hospital and therefore present later
{[}14{]}. In the current study, the rate of complicated appendicitis was
found as 34.27\%, somewhat below the data in the literature. Time to
hospital admission remains the most important factor for perforation,
with a mean of 3.3 days for complicated appendicitis patient group.
Gender plays no role as a factor in the occurrence of complicated
appendicitis.

Comorbid diseases tend to increase morbidity and mortality, although
they have not been identified as a significant factor for perforation
{[}3{]}. For elderly patients, the rate of comorbid disease is observed
to be 43-60.7\% {[}3,6{]}. The rate of comorbid disease in our sample
was higher than the reports in the literature (69.9\%), with no
significant difference between the groups, suggesting that it is not a
risk factor for complicated appendicitis.

There is no clinical symptom, finding, laboratory test, or radiological
method to diagnose acute appendicitis alone. Despite all advancements,
it may still prove difficult to diagnose AA. This proves even more
complicated in geriatric patients {[}15{]}. Advanced radiological
imaging methods facilitate diagnosis. However, particularly in rural
regions, surgeons may not have easy access to such advanced imaging
methods {[}10{]}. Thus, studies have focused on easily accessible and
cost-efficient markers with a high diagnostic value {[}1,9{]}. Surgeons
have been interested in simple laboratory markers that can help diagnose
AA and determine perforation status {[}16{]}. Complete blood count (CBC)
is an ideal marker for these properties. It can be easily accessed and
quickly evaluated in many healthcare institutions, particularly in
emergency rooms {[}10{]}.

White blood cell (WBC) count is the most commonly used laboratory
parameter for diagnosing AA. WBC count often increases in acute
appendicitis patients, but it is not a specific marker because it can
also increase in many other diseases {[}16{]}. One study reports that
WBC has a cut-off value of 10.6, AUC: 0.66, a sensitivity of 71.2\%, and
a specificity of 68.2\% for determining perforation in the elderly
{[}9{]}. Here, WBC count was found to be a marker with high sensitivity
and low specificity for diagnosing AA (Cut-off value:8.97, AUC:0.72,
sensitivity 85\%, specificity 57\%). However, it was not found to be a
biomarker with high diagnostic value for determining complicated
appendicitis.

As the degree of inflammation increases, the neutrophil level increases
and the relative lymphocyte count decreases. Hence, the neutrophil to
lymphocyte ratio (NLR) increases {[}17{]}. NLR has been used as a
biomarker for morbidity, mortality, and survival in many disorders,
including inflammatory and neoplastic diseases {[}16,18{]}. NLR has been
demonstrated to be superior to other traditional infection markers like
WBC, neutrophil, and CRP for determining AA severity {[}9,19{]}. Here,
neutrophil and NLR levels were determined to be biomarkers for
diagnosing AA with similar diagnostic values, while only NLR was a
significant biomarker for determining complicated appendicitis.

MPV is part of routine CBC tests. It is a marker for platelet size and
function. MPV has been examined for its diagnostic and prognostic values
in a number of inflammatory diseases and appendicitis {[}20{]}. However,
there are conflicting findings in the literature, some showing increased
MPV in AA patients {[}21{]}, while others showing decreased MPV
{[}20,22{]}. Similar to the literature, we obtained conflicting results
on MPV. MPV was the highest in the complicated appendicitis group. While
MPV was expected to be the lowest in the negative appendectomy group, it
was the lowest in the uncomplicated appendicitis group. Despite the
conflicting findings, MPV was determined as a marker with the highest
diagnostic value for appendicitis.

PLR is another inflammatory marker that can easily be obtained during
simple hemogram tests. In many cancers and inflammatory events, the
release of proinflammatory cytokines causes proliferation of
megakaryocytes. Also, platelets are known to affect infections.
Therefore, PLR levels can be used for diagnosing appendicitis {[}23{]}.
Y\selectlanguage{polish}ı\selectlanguage{english}ld\selectlanguage{polish}ı\selectlanguage{english}r\selectlanguage{polish}ı\selectlanguage{english}m et al. found PLR to be a useful marker for differentiating
between complicated and uncomplicated appendicitis (cut-off value:
169.7, sensitivity: 74.4\%, specificity: 73.5\%) {[}24{]}. Our findings
revealed that PLR was an important marker for differentiating between
complicated and uncomplicated appendicitis. Although it was found to
have the lowest sensitivity, it had the highest specificity (Cut off
value:190.6, AUC:0.64, sensitivity 50\%, specificity 82\%).

RDW (red cell distribution width) is a subparameter that demonstrates
the distribution volume of circulating erythrocytes. Inflammation
disrupts blood cell maturation, damaging red cell membrane and leading
to increased RDW {[}22{]}. RDW has been shown to increase significantly
in complicated appendicitis, but its diagnostic values have not been
specified {[}25{]}. Comparing those with appendicitis and those without,
no significant difference has been found {[}22,25{]}. Similarly, in the
current study, RDW was found to be a marker for differentiating between
complicated and uncomplicated appendicitis with a high diagnostic value,
but not a significant marker for diagnosing AA. (Cut off value:13.15,
AUC:0.63, sensitivity 69\%, specificity 60\%).

In systemic infection cases, some bacteria, particularly E. coli, cause
hemolysis and endotoxemia. Endotoxemia and bacteria result in impaired
bilirubin excretion from the bile canaliculi. This leads to increased
bilirubin levels in the blood {[}26{]}. It is well known that bilirubin
levels increase in AA. Direct and total bilirubin levels increase in
acute and complex appendicitis and are used as a diagnostic marker
{[}27{]}. Despite limited in number, research has shown
hyperbilirubinemia to be a biomarker for predicting perforation in
geriatric patients {[}9{]}. Here, both direct bilirubin and total
bilirubin levels were found to be important biomarkers for diagnosing
acute appendicitis and predicting complications. Also, they were the
markers with the highest specificity for predicting AA status.

The most frequently used serological indicators for diagnosing acute
appendicitis are leukocyte counts and C-reactive protein (CRP) levels.
CRP is an acute-phase reactant that is synthesized in the liver in
response to infection or inflammation {[}28{]}. Jung et al. found CRP as
a marker for determining perforation in geriatric patients with a high
diagnostic value and a cut-off value of 2.09/mg/dl {[}9{]}. Another
research emphasized its high diagnostic value for determining
perforation in elderly patients (AUC: 0.811 with a cut-off value of
10.19 mg/dl) {[}29{]}.

The most recent SIFIPAC/WSES/SICG/SIMEU guidelines recommend the use of
CRP and leukocyte levels together for diagnosing AA in the elderly
{[}30{]}.

In determining perforation, CRP and TB are noted to be significant
markers with high diagnostic value when used together {[}31{]}. In the
present study, CRP was found to be an important marker for diagnosing
acute appendicitis and determining complication status. Again, similar
to the findings in the literature, TB and CRP were found to increase in
parallel to each other (complicated appendicitis: Cut off value:5.11,
AUC:0.83, sensitivity 72\%, specificity 76\%).

To the best of our knowledge, this is the first study in the literature
to demonstrate the diagnostic efficiency of MPV, PLR, and RDW for
determining acute appendicitis severity in the elderly. We can define
these biomarkers as new diagnostic markers for geriatric age patients.

USG and CT are some of the basic imaging modalities that are most
commonly used for diagnosing AA and determining complications. Yet,
these imaging methods can be difficult to access, leading to further
problems. CT has certain disadvantages, such as high costs, ionizing
radiation, and contrast agent reactions. USG, on the other hand, has
significant disadvantages such as being dependent on the person
performing it and that it cannot be retrospectively examined
{[}32,33{]}. Also, CT has a lower sensitivity in the elderly compared to
the general population {[}34{]}. CT has been reported to have a low
sensitivity for detecting perforated appendicitis without abscess or
phlegm {[}35{]}. In the current study, we found CT to have a sensitivity
of 77.7\% and a specificity of 70\%, while USG had a sensitivity of
74.2\% and a specificity of 18.2\%. USG has a particularly low
specificity.

It is worth mentioning that the length of hospital stay was higher in
the elderly compared to younger patients. Higher complication rates,
prolonged antibiotic treatments, and other comorbid diseases may be
associated with this finding {[}36{]}. Omari et al. found a mean length
of hospital stay of 4.2 days for uncomplicated appendicitis patients and
7.4 days for complicated appendicitis patients {[}3{]}. In our patients,
as expected, the longest length of stay was observed in the complicated
appendicitis group, while the shortest length of stay was observed in
the negative appendectomy group. With a descending order, length of
hospital stay was 6.59, 3.34, and 3.13 days in our groups.

Prognosis for uncomplicated appendicitis is almost similar between young
and elderly patients. However, in the case of perforation, morbidity and
mortality increase dramatically in the elderly {[}8,29{]}. Elderly
appendicitis patients have a postoperative complication rate of 21-60\%
and a mortality rate of 0.97-3\% {[}3,6,7{]}. In our study, the rate of
postoperative complications was 35.7\%, with no mortality. The rate of
complications was found to be higher in the perforated patient group.
The low mortality and morbidity rates in our findings can be explained
by the low number of perforated appendicitis cases.

The major limitation of our study is that it is a retrospective study.
Another limitation is a lack of analysis of symptoms and physical
examination findings, which are crucial for diagnosing AA. Still, our
research had certain strengths, including the high number of patients
compared to most studies in the literature, the analyses of many
biomarkers and obtaining new data, and providing more information by
dividing the patients into three groups.

\textbf{5 CONCLUSIONS}

Elderly patients with abdominal pain present to hospitals later due to
the obscurity of their symptoms and signs. The high rates of
comorbidities in the elderly also lead to more complicated appendicitis.
This results in an increased rate of postoperative complications and
longer hospital stay. The USG and CT modalities used for diagnosis have
almost the same, or sometimes even lower sensitivity and specificity
values compared to the laboratory parameters examined here. Preoperative
WBC, neutrophil, NLR, MPV, CRP, and direct and total bilirubin levels
can be used in the diagnosis of AA in elderly patients. Again, NLR, PLR,
RDW, CRP, and direct and total bilirubin levels can be used to determine
the complications in appendicitis.

\textbf{DISCLOSURES}

The authors declare that there is no conflict of interest.

\section*{DATA AVAILABILITY STATEMENT}

{\label{data-availability-statement}}

The data that support the findings of this study are available on
request from the corresponding author.

\subsection*{AUTHORS CONTRIBUTIONS}

{\label{authors-contributions}}

Conceived and designed the clinical trial: MY, RP. Performed the
experiments: MY, RP. Analysed the data: MY, RP. Wrote the paper: MY, RP.
Conception of the manuscript: MY, RP. Critical revisions: MY, RP.

\textbf{FUNDING:} No funding.

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