Search Results (7,680)

Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their low bioavailability requires nanotechnology solutions, such as liposomes. Methods: In this study, we propose the co-encapsulation of acteoside (ACT) with other natural compounds, cannabidiol (CBD) or naringenin (NG), in a cationic liposomal nanoformulation consisting of DOTAP and POPC lipids, which were prepared using the dry lipid film method. The liposomes were characterized by their physicochemical properties, including particle size, zeta potential, and polydispersity index (PDI), with additional analyses performed using ¹H Nuclear Magnetic Resonance (NMR). Furthermore, biological experiments were performed with U-87 MG astrocytoma and U-138 MG GBM cell lines and non-cancerous MRC-5 lung fibroblasts using the MTT assay and evaluating the expression of Bax and Bcl-xL to evaluate their potential as anticancer agents. Conclusions: The IC₅₀ values for the nanoformulations in U-138 MG cells at 48 h were 6 µM for ACT + CBD and 5 µM for ACT + NG. ACT and CBD or NG demonstrated a potential synergistic effect against GBM in a liposomal formulation. Notably, treatment with ACT + CBD (5 µM) and ACT + NG (5 µM) liposomal formulations significantly upregulated Bax protein level in U-138 cells at both 24 and 48 h. In parallel, ACT + CBD (5 µM) also modulated Bcl-xL protein level in both U-138 MG and U-87 MG cell lines at the same time points. The obtained nanoformulations were homogeneous and stable for 21 days, evidenced by a narrow particle size distribution, a low polydispersity index (PDI) < 0.3, and a positive zeta potential. Full article

Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article

An adult female bottlenose dolphin (Tursiops truncatus) housed at a public oceanarium presented with acute anorexia and lethargy. A blood analysis demonstrated mild leukocytosis, marked azotemia, hyperkalemia, and hyperphosphatemia suggestive of acute kidney injury or renal insufficiency. Ultrasound examination of the dolphin revealed ascites, pleural effusion, bilateral nephrolithiasis, mild hydronephrosis, and bilateral hydroureter consistent with bilateral post-renal obstruction. Initial treatment consisted of antibiotics, oral fluids, and anti-inflammatory treatment. Further imaging diagnosed bilateral obstructing ureteroliths at both ureteral orifice junctions of the urinary bladder. The dolphin’s azotemia and hyperkalemia were nonresponsive to traditional medical management; therefore, peritoneal dialysis was performed for emergent clinical stabilization. Peritoneal dialysis was conducted over 3 days and facilitated the patient to undergo laser lithotripsy of the offending ureteral obstruction. The dolphin made a full recovery following months of intensive medical treatment for complications from peritoneal dialysis and secondary peritonitis. This is the first documented case of successful, though complicated, peritoneal dialysis in a cetacean. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts enteral vitamin D absorption and, consequently, elderly bone metabolism—a specific diagnostic and treatment approach is crucial. Our study aimed to determine the prevalence of vitamin D deficiency and exocrine pancreatic insufficiency (EPI) in orthogeriatric patients. We also evaluated differences in vitamin D deficiency severity between patients with normal and impaired pancreatic function. Furthermore, a short-term monitoring of vitamin D level increases after 12 days of substitution therapy in both groups aimed to inform osteoanabolic therapy for specific high-fracture-risk patients, assessing the influence of pancreatic function on substitution efficacy. Methods: We conducted a retrospective, monocentric cohort study, evaluating data from all patients hospitalized with manifest osteoporosis in an orthogeriatric department during a six-month spring/summer period. Demographic data, relevant comorbidities, the type of fracture, the amount of faecal elastase 1 (CALEX^® Cap Bühlmann), and the serum levels of 25-hydroxyvitamin D (25(OH)D) were assessed. Results: We found a high prevalence (70.6%) of vitamin D deficiency (25(OH)D < 30 µg/L) among all orthogeriatric patients. Of these, 16% met the criteria for mild to severe EPI. The group with normal exocrine pancreatic function showed a higher average vitamin D value, and their increase in vitamin D levels following short-term substitution was up to 100% greater compared to the group with impaired pancreatic function. Notably, 69% of women and 20% of men met the therapeutic threshold for specific osteoanabolic osteoporosis therapy, even without a T-score. Conclusions: Our findings reveal a very high prevalence of vitamin D deficiency and a high prevalence of EPI in orthogeriatric patients. Those with impaired exocrine pancreatic function exhibit lower baseline vitamin D levels and a diminished capacity for vitamin D absorption during short-term monitoring. These results have significant clinical implications for osteoporotic therapy, given that a substantial proportion of patients, particularly women, meet the criteria for specific osteoanabolic treatment. Full article

Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone EVT to elucidate patient characteristics and factors associated with a favorable functional outcome after EVT. Methods: We reviewed all cases of EVT at our institution between February 2018 and February 2022 in the extended time window from 6–24 h. Demographic, clinical, imaging, and procedure co-variates were included. A favorable clinical outcome was defined as a modified Rankin scale of 0–2. We included patients with M1 or internal carotid artery occlusion treated with EVT within 6–24 h after symptom onset. We used a univariate and multivariate logistic regression analysis to identify patient factors associated with a favorable clinical outcome at 90 days. Results: Our study included evaluation of 121 patients who underwent EVT at our comprehensive stroke center. Our analysis demonstrates that a higher recanalization score based on the modified Thrombolysis In Cerebral Infarction (mTICI) scale (2B-3) was a strong indicator of a favorable outcome (OR 7.33; CI 2.06–26.07; p = 0.0021). Our data also showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.0095) and the presence of pre-existing hypertension (p = 0.0035) may also be predictors of an unfavorable outcome (mRS > 2) per our multivariate analysis. Conclusion: Patients without pre-existing hypertension had more favorable outcomes following EVT in the expanded time window. This is consistent with other multicenter data in the expanded time window that demonstrates greater odds of a poor outcome with elevated pre-, peri-, and post-endovascular-treatment blood pressure. Our data also demonstrate that the mTICI score is a strong predictor of favorable outcome, even after controlling for other variables. A lower baseline NIHSS at the time of thrombectomy may also indicate a favorable outcome. Furthermore, the presence of clinical or radiographic mismatch based on the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and NIHSS per DAWN and DEFUSE-3 criteria did not emerge as a predictor of favorable outcome, which is congruent with recent randomized controlled trials and meta-analyses. Full article

Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) or with comorbidities. Methods: We conducted a retrospective observational cohort study from March to December 2024 in an Italian tertiary-care hospital. Adult patients treated in the ER with a single dose of dalbavancin (1500 mg) or oritavancin (1200 mg) for SSTIs were included. Demographic, clinical, and laboratory data were collected. Follow-up evaluations were performed at 14 and 30 days post-treatment to assess outcomes. Results: Nineteen patients were enrolled (median age 59 years; 53% female). Most had lower limb involvement and elevated inflammatory markers. Three patients (16%) were septic. Fourteen patients (74%) were discharged without hospital admission; hospitalization in the remaining cases was due to comorbidities rather than SSTI severity. No adverse drug reactions were observed. At 14 days, 84% of patients had clinical resolution; only 10% had recurrence by day 30, with no mortality nor readmission reported. Conclusions: LALs appear effective and well-tolerated in the ER setting, supporting early discharge and reducing healthcare burden. Broader use may require structured care pathways and multidisciplinary coordination. Full article

Background/Objectives: Low-dose corticosteroids have gained popularity in the treatment of acute respiratory distress syndrome (ARDS); however, the efficacy of high-dose corticosteroids as pulse steroid therapy remains controversial. This study aimed to evaluate the efficacy of pulse steroid therapy in patients with severe ARDS requiring venovenous (V-V) extracorporeal membrane oxygenation (ECMO), where enhanced anti-inflammatory effects may be beneficial. Methods: Using data from the J-CARVE registry, which included patients with severe ARDS managed with V-V ECMO across 24 Japanese hospitals between January 2012 and December 2022, we identified 373 patients treated with corticosteroids. The patients were divided into two groups: pulse steroid therapy and non-pulse steroid therapy. Propensity score matching was performed, and all-cause hospital mortality and ECMO-free days within 28 days were compared between groups. Pulse steroid therapy was defined as methylprednisolone at a dose of 1000 mg/day. Results: After matching, 48 patients were included in each group. The all-cause hospital mortality rates were 41.7% (20/48) in the pulse steroid group and 47.9% (23/48) in the non-pulse steroid group, with no significant difference (odds ratio, 1.28; 95% confidence interval: 0.53–3.12, p = 0.68). The median ECMO-free days were 9.5 (interquartile range [IQR]: 0–17.3) in the pulse steroid group and 3 (IQR: 0–17) in the non-pulse steroid group, showing no significant difference (p = 0.69). Conclusions: Pulse steroid therapy did not improve all-cause hospital mortality or ECMO-free days in patients with severe ARDS who required V-V ECMO. Full article

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

Background/Objectives: The calcaneus is the most commonly injured tarsal bone, potentially resulting in long-term functional deficiencies and disability. The type of treatment mainly depends on fracture type and morphology. Treatment of these fractures can be challenging due to a limited soft tissue envelope and is frequently associated with complications. The aim of this study was to classify fracture types and identify factors associated with in-hospital complications. Methods: Patients with calcaneal fractures treated at our level I trauma center between 1997 and 2017 were included. Demographic data, comorbidities, fracture characteristics, type of treatment, complications and revisions, compliance and accompanying injuries were evaluated. Results: A total of 238 patients (m = 163, f = 75) at a mean age of 40 years sustaining either uni- or bilateral calcaneal fracture resulting in a total of 288 calcaneal fractures. Concomitant injuries were present in 103 patients (35.9%). Traumatic spine lesions were present in 21.9%. Complications were recorded in 59 fractures (20.5%). Open fractures were more likely to develop complications (76.0% vs. 15.2%, p < 0.001). Significant complication (33% vs. 14%, p < 0.001) and wound complication rates (29% vs. 10%, p < 0.001) were found in multiple-injured patients. All open fractures were surgically treated on the day of admission. In calcaneal fractures with a Böhler angle below 0 degrees, more complications were seen (33% vs. 17%, p < 0.05). Conclusions: High complication rates following calcaneal fractures were detected, with an increased likelihood in open fractures and in patients with multiple injuries. A negative Böhler angle was associated with worse outcomes. Full article

Objectives: Topical lubricants are the fundamental treatment for dry eye disease (DED). However, the molecular mechanisms underlying their efficacy remain unknown. Here, the protective effects of Thealoz^® Duo with 3% trehalose and 0.15% hyaluronic acid are investigated in DED patients by a longitudinal clinical study and subsequent elucidation of the tear proteome and cell signaling changes. Methods: Participants were classified as moderate to severe DED (DRY, n = 35) and healthy (CTRL, n = 23) groups. Specific DED subgroups comprising evaporative (DRYlip) and aqueous-deficient with DRYlip (DRYaqlip) were also classified. Only DED patients received Thealoz^® Duo. All participants were clinically examined before (day 0, T1) and after the application of Thealoz^® Duo at day 28 (T2) and day 56 (T3). Next, 174 individual tear samples from all groups at three time-points were subjected to proteomics analysis. Results: Clinically, Thealoz^® Duo significantly improved the ocular surface disease index at T2 vs. T1 (DRY, p = 1.4 × 10⁻²; DRYlip, p = 9.2 × 10⁻³) and T3 vs. T1 (DRY, p = 2.1 × 10⁻⁵; DRYlip, p = 1.2 × 10⁻⁴), and the tear break-up time at T3 vs. T1 (DRY, p = 3.8 × 10⁻²; DRYlip, p = 1.4 × 10⁻²). Thealoz^® Duo significantly ameliorated expression of inflammatory response proteins (p < 0.05) at T3, which was observed at T1 (DRY, p = 3.4 × 10⁻⁴; DRYlip, p = 7.1 × 10⁻³; DRYaqlip, p = 2.7 × 10⁻⁸). Protein S100-A8 (S100A8), Alpha-1-antitrypsin (SERPINA1), Annexin A1 (ANXA1), and Apolipoprotein A-I (APOA1) were found to be significantly reduced in all the DED subgroups. The application of Thealoz^® Duo showed the therapeutic characteristic of the anti-inflammatory mechanism by promoting the expression of (Metalloproteinase inhibitor 1) TIMP1 in all the DED subgroups. Conclusions: Thealoz^® Duo substantially improved the DED symptoms and restored the functionality of the tear lipid layer to near normal in DRYlip and DRY patients by ameliorating inflammation. Notably, this study unravels the novel mechanistic alterations underpinning the healing effects of Thealoz^® Duo in DED subgroups in a time-dependent manner, which supports the improvement in corresponding clinical attributes. Full article

Background/Objectives: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia exhibiting 90% mortality without prompt treatment. The aim of this study was to investigate the association of therapeutic plasma exchange (TPE)-treated TTP in end-stage renal disease (ESRD) patients with mortality, demographics, and clinical comorbidities. We queried the United States Renal Data System for ESRD patients starting dialysis between 1 January 2005 and 31 December 2018, using International Classification of Diseases (ICD)-9 and ICD-10 codes for thrombotic microangiopathy, with a TPE procedure code entered within 7 days. Methods: Cox proportional hazards models were used to assess mortality, adjusting for demographic and clinical factors. Results: Among 1,155,136 patients, increased age [adjusted odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.94–0.96]; black race (OR = 0.67, CI: 0.51–0.89); and Hispanic ethnicity (OR = 0.43, CI: 0.28–0.66) were associated with a lower risk of TPE-treated TTP diagnosis, whereas female sex (OR = 1.59, CI: 1.25–2.02) and tobacco use (OR = 2.08, CI: 1.58–2.75) had a higher risk. A claim for TPE-treated TTP carried a lower risk of death (adjusted hazard ratio = 0.024, CI: 0.021–0.028). Female sex, black race, Hispanic ethnicity, and hypothyroidism were also associated with decreased all-cause mortality. Conclusions: These findings suggest that ESRD patients with TPE-treated TTP are significantly protected from mortality compared with ESRD patients without this diagnosis. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article

Ceftazidime–avibactam (CAZ-AVI) is a second-generation intravenous β-lactam/β-lactamase inhibitor combination. In recent years, substantial evidence has emerged regarding the efficacy and safety of CAZ-AVI. However, data on its use in critically ill patients remain limited. Background/Objectives: This multicenter, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure—defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy—in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Results: Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapse or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. Furthermore, treatment failure was more frequent among immunosuppressed individuals, particularly liver transplant recipients. Conclusions: This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies. Full article

Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This meta-analysis aims to determine which inotropic agent may be more effective in this clinical scenario. Methods: A systematic review and meta-analysis were conducted, including data from randomized clinical trials (RCTs) comparing levosimendan and dobutamine in patients with septic shock and persistent hypoperfusion. Summary effect estimates, including odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs), were calculated using a random-effects model. Trial sequential analysis (TSA) was also performed. Results: Of 244 studies screened, 11 RCTs were included. Levosimendan was associated with a reduction in in-hospital mortality (OR 0.64; 95% CI: 0.47; 0.88) and ICU length of stay (SMD 5.87; 95% CI: –8.37; 20.11) compared with dobutamine. Treatment with levosimendan also resulted in significant reductions in BNP (SMD –1.87; 95% CI: –2.45; −1.2) and serum lactate levels (SMD –1.63; 95% CI: –3.13; −0.12). However, TSA indicated that the current evidence is insufficient to definitively confirm or exclude effects on in-hospital and 28-day mortality. Conclusions: Levosimendan may improve hemodynamics, tissue perfusion, and biomarkers, and may reduce in-hospital mortality and ICU length of stay in patients with SICM compared with dobutamine. However, TSA highlights the need for further studies to inform clinical practice and optimize inotrope selection. Full article