**Table 1.** Tokyo Guidelines (TG13/TG18) severity risk scale [9,25].

\* WBC—white blood cells.

The management of acute cholecystitis was according to the Tokyo Guidelines 2018 flowchart [25] based on the severity of symptoms, ASA and CCI index. Emergency laparoscopic cholecystectomy was performed as soon as possible to be performed safely, within a time frame of 96 h after the admission. Broad spectrum intravenous antibiotic therapy was used in all cases. In mild cases, we used intravenous ceftriaxone (1 g/12 h), and in medium and severe cases we used a combination of ceftriaxone or piperacillin/tazobactam (4 g + 0.5 g/8 h) and metronidazole (1 g/12 h). The antibiotic therapy was initiated in emergency and continued up to 24–48 h postoperatively, in cases with a favorable outcome. In cases with pyocholecystitis, parietal micro-abscesses, or pericholecystic abscess, bile was sent for a microbiological exam, and antibiotic therapy was adjusted later in correlation with the antibiogram. Low-molecular-weight Heparin for thrombosis prophylaxis was used as a routine pre and postoperatively during the hospital stay, according to body weight and comorbidities, in doses starting from 0.4 mL/day to 1.2 mL/day.

Conversion to open surgery was used as a second option of bailout procedure, after "fundus first", when technical difficulties were encountered and critical view of safety in the Calot triangle was not achieved. Subtotal cholecystectomy was considered a technical solution in difficult cases, and it can be performed either laparoscopically or by open surgery, depending on the surgeon's experience and the local technical conditions. Drainage was used in all these patients.

Patients with ASA ≥ 3 and CCI ≥ 6 or sepsis underwent fluid rebalance and general supportive care before surgery.

#### *2.2. Data Comparison and Statistical Analysis*

The patients included in the study group were divided into 4 age-subgroups: A: ≤49 years; B: 50–64 years; C: 65–79 years; D: ≥80 years.

The main outcomes were: mortality rate and incidence of major systemic and surgery related complications. Secondly, the rate of laparoscopic cholecystectomies and the rate of conversion were analyzed comparatively in the four age-subgroups. A statistical analysis was performed to assess the association correlations between age and anesthetic-surgical risk, the severity forms of acute cholecystitis and post-operatory outcomes.

Pearson chi square, Fisher's exact test and the Linear-by-Linear association test (Mantel-Haenszel test for trend) were used to evaluate the association between discrete variables, the ANOVA test was used for continuous variables and Fisher's linear discriminant analysis was used for multivariate analysis. IBM SPSS Statistics 22 was applied.

In order to describe the preoperative and intraoperative patients' characteristics which determined the applied surgical procedure (LC = Laparoscopic Cholecystectomy, Conversion or OC = Open Cholecystectomy), we have used the stepwise variant of Fisher's linear discriminant analysis. The Canonical Discriminant Function is displayed in standardized form in order to allow the comparison of the importance of each variable. Cross-validation models were used to evaluate the statistical power of discrimination.
