Nikola Lađević

Background and Objectives: Ketamine and magnesium sulfate (MgSO₄) are NMDA receptor antagonists that act through distinct mechanisms. Preclinical data indicate that their analgesic interaction is sequence-dependent: ketamine administered before MgSO₄ produces synergistic antinociception, whereas the reversed sequence is antagonistic. The primary outcomes were postoperative pain intensity (Numerical Rating Scale, NRS 0–10, at rest and on movement) and cumulative intravenous morphine consumption over 48 h, evaluated in patients undergoing open radical nephrectomy to test the hypothesis of sequence-dependent analgesic interaction. Materials and Methods: In this randomized, double-blind, placebo-controlled trial, 208 patients scheduled for elective open radical nephrectomy received two sequential intravenous boluses intraoperatively: Drug A immediately after induction, Drug B 10 min later. Agents were ketamine 0.2 mg/kg, MgSO₄ 15 mg/kg, or placebo (0.9% NaCl) in all nine possible combinations. Primary outcomes were postoperative pain intensity (NRS 0–10, at rest and on movement) and cumulative intravenous morphine consumption, assessed at 14 time points over 48 h. Secondary outcomes included sedation, nausea, vomiting, and the presence of hallucinations. Results: The ketamine → MgSO₄ (K → Mg) sequence significantly reduced NRS pain scores compared to placebo at multiple time points, including 30 min, 1 h, 3 h, 6 h, and 32 h postoperatively, with differences exceeding the minimum clinically important difference of 2 NRS points at the earliest assessments. The MgSO₄ → ketamine (Mg → K) sequence did not differ from placebo at any time point. Cumulative morphine consumption was comparable across groups. No hallucinations or psychomimetic events were observed. Conclusions: Intraoperative ketamine followed by MgSO₄ (K → Mg) provides clinically meaningful postoperative analgesia after open radical nephrectomy; the reversed sequence (Mg → K) offers no benefit over placebo. These findings provide the first clinical confirmation of sequence-dependent NMDA receptor antagonism and support the K → Mg protocol as a safe, simple addition to multimodal perioperative analgesia. Trial registration: ISRCTN registry, ISRCTN83633282.

Introduction. Cervical cancer, as a global health problem, is most commonly associated with HPV infection. The incidence is rising among women of reproductive age. The challenge is that standard treatment is radical hysterectomy that remains a serious problem for women who still wish to conceive. Fertilitysparing surgery is possible in strictly controlled cases, but pregnancy afterwards is still an issue. Case outline. A 32-year-old, nulliparous patient with a diagnosis of early-stage invasive squamous cell cervical cancer is presented. After evaluation and only after selection criteria were met, radical abdominal trachelectomy with pelvic lymph node dissection was performed. Final histological diagnosis revealed that cancer infiltrated the entire depth of the specimen, with malignant cells present at the lateral resection margin. Radical hysterectomy was indicated, but the patient refused. After a year, the patient conceived spontaneously and had a successful pregnancy. Conclusion. The fertility-sparing treatment for early-stage cervical cancer is an oncologically safe option in carefully selected patients. The pregnancy afterwards remains high risk and needs close follow-up to optimize both maternal and fetal outcomes.

Background: Postoperative delirium (POD) is one of the most common surgical complications in elderly patients. This study investigated the incidence of and perioperative risk factors for POD following urological surgery. Methods: A total of 162 male patients aged ≥50 years undergoing elective major urological surgery under general anesthesia from May 2024 to March 2025 were included in this prospective observational study. Delirium was assessed using CAM-ICU twice a day for five postoperative days. Groups with and without delirium were compared, and perioperative predictors of delirium were analyzed. Multivariate regression analysis was used to identify independent risk factors for POD. Results: Overall, 16% of patients developed delirium during the follow-up period. Patients with POD were significantly older (mean age, 73.3 ± 5.2 years vs. 66.3 ± 7.2, p < 0.001), had more comorbidities, and lived in rural areas. Atrial fibrillation and COPD were particularly significant. The incidence of POD was higher in patients with mild/moderate alcohol consumption than in those who never drink. Analysis of intraoperative factors revealed a significant difference between groups in the presence of intraoperative hypotension and blood transfusion. Patients with delirium had more severe postoperative pain. Optimal cutoff values of age (≥67.5), number of comorbidities (≥2), preoperative MMSE score (≤25.5), and postoperative NRS score (≥4.85) were determined using ROC curves. The multivariate analysis identified age ≥ 67.5 years, COPD, mild/moderate alcohol consumption, preoperative MMSE score ≤ 25.5, intraoperative hypotension, and postoperative NRS score ≥ 4.85 as independent risk factors in this cohort. Conclusions: Considering that some of the above risk factors can be modified, it is necessary to emphasize that the prevention of POD is possible and should be one of the treatment priorities in older patients.

Local anaesthetics are widely used for penile and genital surgery, with techniques tailored to the specific nerve supply and dermatomal distribution of the genitalia. For penile and genital surgery, local infiltration (ring block), dorsal penile nerve block, and pudendal nerve block are the most common techniques. The pudendal nerve block providing optimal analgesia for extensive penile or genital surgeries, while local infiltration and topical agents are appropriate for less invasive interventions. The recommended technique for providing local anesthesia for scrotal surgery is ultrasound-guided ilioinguinal and genitofemoral nerve blocks. This approach targets the nerves responsible for sensory innervation of the scrotum and adjacent regions, providing effective intraoperative anesthesia and postoperative analgesia.

Introduction: The increased inflammatory response after knee arthroplasty (TKA) is a result of bone and soft tissue trauma whose extensive reactions contribute to postoperative morbidity and mortality. Methods: After elective TKA, 200 patients were included in this prospective cohort study. In one group of patients the adductor block and IPACK block were applied, while in the second group there were no blocks. Results: In the group with blocks fewer patients experienced pain at rest with lower intensity (1.18±0.76 vs. 3.35±1.18 p<0.001). In the group without blocks, pain was more intense when coughing (1.7±0.52 vs. 3.72±1.61 p<0.001) and during active movements of the operated leg (1.67±0.83 vs. 3.78±1.94 p<0.001). In the first 24 hours after surgery, in the group with blocks, 22% of patients needed opioids in a dose of 9.64±3.21, while all patients in the group without blocks needed opioids in a dose of 30.94±11.47. Postoperatively, a statistically significant difference between the groups was observed in WBC, CRP, ESR, and albumin levels on the 1st, 3rd, and 5th days. Three months after TKA, the KOOS score was statistically higher in the group with blocks (92.6±11.73 vs 85.65±17.49 p<0.001). Conclusion: The combination of nerve blocks provides adequate postoperative analgesia enabling early rehabilitation, reducing morphine consumption, reducing the count of WBC, CRP, ESR, and albumin (1st, 3rd, and 5th day postoperatively), and positively affecting the functional status three months after surgery. Identification and influence on factors that reduce the local and systemic inflammatory response is vital in improving recovery after TKA.

Pain is a major health issue representing a leading cause of disability. It affects millions of adults worldwide and impose significant burdens on society, healthcare systems, and personal well-being. The management of chronic pain presents a major challenge for healthcare professionals, as there is no single or universally effective treatment. Conventional treatments such as opioids and nonsteroidal anti-inflammatory drugs are first line treatment, but they carry significant risks and limitations, including addiction, tolerance, dependence, adverse effects, especially when used long term. As a result, additional approaches are needed to provide effective and safe chronic pain relief. Non-pharmacological pain management strategies represent a promising domain especialy as a part of complementary tailored to individual needs and integrated to contemporary pain medicine.

Introduction: Extracorporeal shock wave lithotripsy (ESWL) used to be performed under general anesthesia. Today, although it is a painful procedure, it is performed under analgosedation. The aim of the study was to determine the severity of acute pain associated with ESWL using two comparative protocols for preemptive analgesics: tramadol vs. ketoprofen plus tapentadol. Methods: A clinical prospective randomized cohort study included 200 patients of both sexes aged 18-80 years who were divided into two groups: group 1 received a combination of ketoprofen 100 mg/ tramadol 50 mg i.m. 30 minutes before surgery; group 2 received tapentadol IR 50 mg orally, 1 hour before surgery. Pain intensity (NRS) and complications were recorded before, during and at the end of the procedure, respectively. Results: No difference was found in the preoperative characteristics of patient population, size and localization of the stone. Dimensions of kidney-localized stones were significantly higher in group 2 compared to group 1 (T test .000). There was a statistically significant increase in pain intensity before and during the procedure as well as pain intensity decrease during and after the procedure in each group (T test .000). In group 2, 10% of patients experienced severe pain during the procedure, compared to 3%of patients in group 1 (Mann-Witney 0.005). In the severe pain subgroups of each patient group, drowsiness occurred in 5% of patients in group 2, which was significantly more than the 1% in group 1 (overall incidence in both groups was 25%). Conclusion: Although both protocols offered average moderate pain intensity during the procedure, severe pain and nausea were observed more frequently in the tapentadol group, which was related to stone size and JJ stent insertion.

Background and Objectives: Smartphone use has been rapidly increasing worldwide, which has brought possible smartphone addiction into the focus of research. In order to identify potential smartphone addicts, several scales were developed to assess smartphone addiction. Among them, the Smartphone Addiction Scale was frequently used. The study aimed to test the reliability and validity of the Serbian version of the SAS-SV and estimate smartphone addiction prevalence among medical students. Materials and Methods: The study was conducted in December 2018 on a convenience sample of 323 third-year medical students. The cross-cultural adaptation was performed following the well-established guidelines for cross-cultural adaptation of self-reported measures. Exploratory factor analysis was used to examine the structure of the questionnaire. Factor extraction was performed by principal component analysis with Varimax rotation. For test–retest reliability, students completed the questionnaire twice within seven days. Results: The Serbian version of the SAS-SV showed good internal consistency (Cronbach’s alpha = 0.89) and excellent reliability for test–retest scores (ICC = 0.94, 95% CI = 0.92–0.96). Factor analysis supported the extraction of one factor, which explained 51.538% of the variance. To explore convergent validity furthermore, the SAS-SV was correlated with time indicators of smartphone use. According to cut-off values for the SAS-SV score, 19.5% of students could be regarded as “addicted”, and often spent more time on smartphones and social networks on working days and weekends than “not addicted” students. Conclusions: The Serbian version of the SAS-SV is a reliable and valid instrument for detecting smartphone addiction among university students. Further research on this issue is encouraged to enable a better understanding of this ever-increasing public health issue.