Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review.

BACKGROUND/OBJECTIVES: Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. Intravitreal complement inhibitors are an emergent approach in the treatment of AMD, which have had encouraging results. This systematic review analyzes the outcomes and safety of complement inhibitor therapies for GA in AMD cases. METHODS: A comprehensive search on the PubMed and Web of Science databases returned 18 studies involving various complement inhibitor agents, with a total of 4272 patients and a mean follow-up of 68.2 ± 20.4 weeks. RESULTS: Most treated patients were white (96.8%) and female (55.8%), with a mean age of 78.3 ± 7.8 years and a mean GA area of 8.0 ± 3.9 mm2. There were no differences in visual function change between treated and control participants. The mean GA area change was 2.4 ± 0.7 mm2 in treated participants vs. 2.7 ± 0.8 mm2 in control groups (p < 0.001). The ocular and systemic side effects were similar to those of intravitreal anti-VEGF. A less-understood effect was that of the onset of choroidal neovascularization (CNV) in 1.1-13% of patients; this effect was found to be more frequent in patients with neovascular AMD in the fellow eye or nonexudative CNV in the study eye at baseline. CONCLUSIONS: Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes.

The Value of Systemic Inflammatory Indices for Predicting Early Postoperative Complications in Colorectal Cancer.

Background and Objectives: Systemic inflammatory indices have been largely investigated for their potential predictive value in multiple inflammatory, infectious, and oncological diseases; however, their value in colorectal cancer is still a subject of research. This study investigates the dynamics of pre- and postoperative values of NLR, PLR, SII, and MLR in patients with colorectal cancer and their predictive value for early postoperative outcomes. Materials and Methods: A 2-year retrospective cohort study was performed on 200 patients operated for colorectal adenocarcinoma. Systemic inflammatory indices were calculated based on complete blood count preoperatively and on the first and sixth postoperative days. The patients were divided into two groups based on their emergency or elective presentation. The pre- and postoperative values of serum inflammatory biomarkers and their correlations with postoperative outcomes were separately analyzed for the two study subgroups. Results: There were no significant differences in sex distribution, addressability, associated comorbidities, or types of surgery between the two groups. Patients in the emergency group presented higher preoperative and postoperative values of WBC, neutrophils, NLR, and SII compared to elective patients. The postsurgery hospital stays correlated well with pre- and postoperative day one and day six values of NLR (p = 0.001; 0.02; and <0.001), PLR (p < 0.001), SII (p = 0.037; <0.001; <0.001), and MLR (p = 0.002; p = 0.002; <0.001). In a multivariate analysis, reintervention risk was higher for emergency presentation and anemia, and lower in right colon cancer. In the emergency group, a multivariate model including age, MLR PO1, and pTNM stage was predictive for severe postoperative complications (AUC ROC 0.818). First-day postoperative inflammatory indices correlated well with sepsis, with the best predictive value being observed for the first postoperative day NLR (AUC 0.836; sensibility 88.8%; specificity 66.7%) and SII (AUC 0.796; sensitivity 66.6%; specificity 90%). For elective patients, the first postoperative day PLR and anemia were included in a multivariate model to predict Clavien-Dindo complications graded 3 or more (AUC ROC 0.818) and reintervention (AUC ROC 0.796). Conclusions: Easy-to-calculate and inexpensive systemic inflammatory biomarkers could be useful in predicting early postoperative outcomes in colorectal cancer for both elective and emergency surgery.

Factors Affecting the Efficiency of Near-Infrared Indocyanine Green (NIR/ICG) in Lymphatic Mapping for Colorectal Cancer: A Systematic Review.

As laparoscopy gained global popularity in oncologic surgery, the challenge of detecting lymph nodes spurred researchers to explore innovative techniques and approach the situation from a fresh perspective. While many proposed methods have faded into obscurity, the utilization of indocyanine green (ICG) in the surgical treatment of oncologic patients has continued to advance. The immense potential of this dye is widely acknowledged, yet its full extent and limitations in lymphatic mapping for colorectal cancer remain to be precisely determined. This article aims to assess the magnitude of its potential and explore the constraints based on insights from clinical studies published by pioneering researchers. A systematic review of the existing literature, comprising articles in English, was conducted using the Scopus, PubMed, and Springer Link databases. The search employed keywords such as "colorectal cancer" AND/OR "indocyanine green," "fluorescence" AND/OR "lymphatic mapping" AND/OR "lymph nodes." Initially identifying 129 articles, the application of selection criteria narrowed down the pool to 10 articles, which served as the primary sources of data for our review. Despite the absence of a standardized protocol for the application of ICG in colorectal cancer, particularly in the context of lymphatic mapping, the detection rates have exhibited considerable variation across studies. Nevertheless, all authors unanimously regarded this technique as beneficial and promising. Additionally, it is advocated as an adjunctive tool to enhance the accuracy of cancer staging. Near-infrared (NIR)-enhanced surgery holds the promise of transforming the landscape of oncologic surgery, emerging as a valuable tool for surgeons. However, the absence of a standardized technique and the subjective nature of result assessment impose limitations on the potential of this method. Consequently, it can be inferred that the establishment of a universally accepted protocol, encompassing parameters such as dose, concentration, technique, and site of administration of ICG, along with the optimal time needed for fluorescence visualization, would enhance the outcomes. Emphasizing the accurate selection of patients is crucial to prevent the occurrence of false-negative results.

Predictive Factors for Difficult Laparoscopic Cholecystectomies in Acute Cholecystitis.

Laparoscopic cholecystectomy (LC) is the gold standard treatment in acute cholecystitis. However, one in six cases is expected to be difficult due to intense inflammation and suspected adherence to and involvement of adjacent important structures, which may predispose patients to higher risk of vascular and biliary injuries. In this study, we aimed to identify the preoperative parameters with predictive value for surgical difficulties. A retrospective study of 255 patients with acute cholecystitis admitted in emergency was performed between 2019 and 2023. Patients in the difficult laparoscopic cholecystectomy (DLC) group experienced more complications compared to the normal LC group (33.3% vs. 15.3%, p < 0.001). Age (p = 0.009), male sex (p = 0.03), diabetes (p = 0.02), delayed presentation (p = 0.03), fever (p = 0.004), and a positive Murphy sign (p = 0.007) were more frequently encountered in the DLC group. Total leukocytes, neutrophils, and the neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the DLC group (p < 0.001, p = 0.001, p = 0.001 respectively). The Tongyoo score (AUC ROC of 0.856) and a multivariate model based on serum fibrinogen, thickness of the gallbladder wall, and transverse diameter of the gallbladder (AUC ROC of 0.802) showed a superior predictive power when compared to independent parameters. The predictive factors for DLC should be assessed preoperatively to optimize the therapeutic decision.

Association Between Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) With Diabetic Retinopathy in Type 2 Diabetic Patients.

Diabetic retinopathy (DR) is one of the main causes of blindness worldwide, but an effective screening is challenging due to limited available retina specialists. Finding novel biomarkers could help clinical decision in prioritizing ophthalmological consultation in patients at risk of developing severe DR. This study aims to investigate the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the presence and severity of DR in patients with T2DM. A retrospective study was performed on 90 patients with T2DM admitted in the Ophthalmology Clinic, Emergency University Hospital Bucharest in Bucharest, Romania, between March 2022 and March 2023, for routine cataract surgery. The cases were divided into three groups according to the severity of DR: no DR (noDR), non-proliferative diabetic retinopathy (NPDR), and proliferative DR (PDR) groups. NLR values raised significantly in the PDR group, no DR group (p = 0.003), and NPDR group (p = 0.026), while PLR values did not differ statistically significant among the groups (p = 0.059). No difference in terms of age, sex, HbA1C, and comorbidities were observed. In the multivariate analysis, the NLR (OR = 2.01, [1.29; 3.14], p = 0.0019) and diabetic nephropathy (OR = 3.84, [1.23; 11.98], p = 0.0203) were associated with higher rates of PDR. NLR may be a promising tool in the risk stratification of T2DM patients with DR.

The Significance of Preoperative Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Systemic Inflammatory Index (SII) in Predicting Severity and Adverse Outcomes in Acute Calculous Cholecystitis.

The prediction of severity in acute calculous cholecystitis (AC) is important in therapeutic management to ensure an early recovery and prevent adverse postoperative events. We analyzed the value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammatory index (SII) to predict advanced inflammation, the risk for conversion, and postoperative complications in AC. Advanced AC was considered the cases with empyema, gangrene, perforation of the gallbladder, abscesses, or difficulties in achieving the critical view of safety. A 3-year retrospective was performed on 235 patients admitted in emergency care for AC. The NLR was superior to the PLR and SII in predicting advanced inflammation and risk for conversion. The best predictive value was found to be at an NLR "cut-off" value of >4.19, with a sensitivity of 85.5% and a specificity of 66.9% (AUC = 0.824). The NLR, SII, and TG 13/18 correlate well with postoperative complications of Clavien-Dindo grade IV (p < 0.001 for all variables) and sepsis. For predicting early postoperative sepsis, TG 13/18 grading >2 and NLR > 8.54 show the best predicting power (AUC = 0.931; AUC = 0.888, respectively), although not significantly higher than that of the PLR and SII. The NLR is a useful biomarker in assessing the severity of inflammation in AC. The SII and PLR may be useful in the prediction of systemic inflammatory response.

When Not to Operate on Acute Cases-A Surgeon's Perspective on Rapid Assessment of Emergency Abdominopelvic Computed Tomography.

Clinical problem solving evolves in parallel with advances in technology and discoveries in the medical field. However, it always reverts to basic cognitive processes involved in critical thinking, such as hypothetical-deductive reasoning, pattern recognition, and compilation models. When dealing with cases of acute abdominal pain, clinicians should employ all available tools that allow them to rapidly refine their analysis for a definitive diagnosis. Therefore, we propose a standardized method for the quick assessment of abdominopelvic computed tomography as a supplement to the traditional clinical reasoning process. This narrative review explores the cognitive basis of errors in reading imaging. It explains the practical use of attenuation values, contrast phases, and windowing for non-radiologists and details a multistep protocol for finding radiological cues during CT reading and interpretation. This systematic approach describes the salient features and technical tools needed to ascertain the causality between clinical patterns and abdominopelvic changes visible on CT scans from a surgeon's perspective. It comprises 16 sections that should be read successively and that cover the entire abdominopelvic region. Each section details specific radiological signs and provides clear explanations for targeted searches, as well as anatomical and technical hints. Reliance on imaging in clinical problem solving does not make a decision dichotomous nor does it guarantee success in diagnostic endeavors. However, it contributes exact information for supporting the clinical assessments even in the most subtle and intricate conditions.

When Critical View of Safety Fails: A Practical Perspective on Difficult Laparoscopic Cholecystectomy.

The incidence of common bile duct injuries following laparoscopic cholecystectomy (LC) remains three times higher than that following open surgery despite numerous attempts to decrease intraoperative incidents by employing better training, superior surgical instruments, imaging techniques, or strategic concepts. This paper is a narrative review which discusses from a contextual point of view the need to standardise the surgical approach in difficult laparoscopic cholecystectomies, the main strategic operative concepts and techniques, complementary visualisation aids for the delineation of anatomical landmarks, and the importance of cognitive maps and algorithms in performing safer LC. Extensive research was carried out in the PubMed, Web of Science, and Elsevier databases using the terms "difficult cholecystectomy", "bile duct injuries", "safe cholecystectomy", and "laparoscopy in acute cholecystitis". The key content and findings of this research suggest there is high intersocietal variation in approaching and performing LC, in the use of visualisation aids, and in the application of safety concepts. Limited papers offer guidelines based on robust data and a timid recognition of the human factors and ergonomic concepts in improving the outcomes associated with difficult cholecystectomies. This paper highlights the most relevant recommendations for dealing with difficult laparoscopic cholecystectomies.

The Value of White Cell Inflammatory Biomarkers as Potential Predictors for Diabetic Retinopathy in Type 2 Diabetes Mellitus (T2DM).

The pathogenesis of diabetic retinopathy is still challenging, with recent evidence proving the key role of inflammation in the damage of the retinal neurovascular unit. This study aims to investigate the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic inflammation index (SII) for diabetic retinopathy (DR) and its severity. We performed a retrospective study on 129 T2DM patients, divided into three groups: without retinopathy (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). NLR, MLR, and SII were significantly higher in the PDR group when compared to NDR and NPDR (3.2 ± 1.6 vs. 2.4 ± 0.9 and 2.4 ± 1.1; p = 0.005; 0.376 ± 0.216 vs. 0.269 ± 0.083 and 0.275 ± 0.111, p = 0.001; 754.4 ± 514.4 vs. 551.5 ± 215.1 and 560.3 ± 248.6, p = 0.013, respectively). PDR was correlated with serum creatinine (OR: 2.551), NLR (OR: 1.645), MPV (OR: 1.41), and duration of diabetes (OR: 1.301). Logistic regression analysis identified three predictive models with very good discrimination power for PDR (AUC ROC of 0.803, 0.809, and 0.830, respectively): combining duration of diabetes with NLR, MLR, and, respectively, PLR, MPV, and serum creatinine. NLR, MPV, SII, and LMR were associated with PDR and could be useful when integrated into comprehensive risk prediction models.

Gut Microbiota Dysbiosis in Diabetic Retinopathy-Current Knowledge and Future Therapeutic Targets.

Diabetic retinopathy is one of the major causes of blindness today, despite important achievements in diagnosis and therapy. The involvement of a gut-retina axis is thought to be a possible risk factor for several chronic eye disease, such as glaucoma, age-related macular degeneration, uveitis, and, recently, diabetic retinopathy. Dysbiosis may cause endothelial disfunction and alter retinal metabolism. This review analyzes the evidence regarding changes in gut microbiota in patients with DR compared with diabetics and healthy controls (HCs). A systematic review was performed on PubMed, Web of Science, and Google Scholar for the following terms: "gut microbiota" OR "gut microbiome" AND "diabetic retinopathy". Ultimately, 9 articles published between 2020 and 2022 presenting comparative data on a total of 228 T2DM patients with DR, 220 patients with T2DM, and 118 HCs were analyzed. All of the studies found a distinctive microbial beta diversity in DR vs. T2DM and HC, characterized by an altered Firmicutes/Bacteroidetes ratio, a decrease in butyrate producers, and an increase in LPS-expressing and pro-inflammatory species in the Bacteroidetes and Proteobacteria phyla. The probiotic species Bifidobacterium and Lactobacillus were decreased when compared with T2DM. Gut microbiota influence retinal health in multiple ways and may represent a future therapeutic target in DR.

Retrospective Study from a Single Center in Romania of 347 Renal Transplant Patients Treated with Tacrolimus, Mycophenolate, and Steroids to Evaluate the Association Between Anti-HLA Antibodies and 5-Year Graft Survival.

BACKGROUND Kidney transplantation is the most recommended treatment in chronic kidney disease. The recipient's immune system reacts to a kidney graft as to an alloantigen by producing antibodies (anti-human leukocyte antigens [HLAs]). Although immunosuppressive therapy is used to overcome this problem, the long-term survival of a kidney graft after 5 years remains low. This retrospective study from a single center in Romania of 347 renal transplant patients treated with tacrolimus, mycophenolate, and steroids aimed to evaluate the association between anti-HLA antibodies and 5-year graft survival. MATERIAL AND METHODS Anti-HLA antibodies were screened and identified using the Luminex method, while tacrolimus levels were monitored using the chemiluminescent assay. RESULTS Twenty-seven patients had pre-existing anti-HLA antibodies, while 320 patients did not. Of the 320 patients, 15% developed anti-HLA antibodies following kidney transplantation. The intrapatient minimum blood level of tacrolimus (cut-off value: 4.6 ng/mL) after transplantation was significantly associated with the risk of de novo anti-HLA antibodies (P<0.001). In patients with or without de novo anti-HLA antibodies, the 5-year allograft survival rate was 77.1% vs 90.8% (P=0.004). After Bonferroni correction, donor age (P=0.001), and donor type (P<0.0001) were statistically associated with the risk of allograft rejection. CONCLUSIONS This study showed that anti-HLA antibodies at 5 years after kidney transplantation were significantly associated with graft failure. The findings support previous studies and indicate that monitoring of anti-HLA antibodies should be considered in patients with renal transplant.

PLGA Nanoparticles Uptake in Stem Cells from Human Exfoliated Deciduous Teeth and Oral Keratinocyte Stem Cells.

Polymeric nanoparticles have been introduced as a delivery vehicle for active compounds in a broad range of medical applications due to their biocompatibility, stability, controlled release of active compounds, and reduced toxicity. The oral route is the most used approach for delivery of biologics to the body. The homeostasis and function of oral cavity tissues are dependent on the activity of stem cells. The present work focuses, for the first time, on the interaction between two types of polymeric nanoparticles, poly (lactic-co-glycolic acid) or PLGA and PLGA/chitosan, and two stem cell populations, oral keratinocyte stem cells (OKSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). The main results show that statistical significance was observed in OKSCs uptake when compared with normal keratinocytes and transit amplifying cells after 24 h of incubation with 5 and 10 µg/mL PLGA/chitosan. The CD117+ SHED subpopulation incorporated more PLGA/chitosan nanoparticles than nonseparated SHED. The uptake for PLGA/chitosan particles was better than for PLGA particles with longer incubation times, yielding better results in both cell types. The present results demonstrate that nanoparticle uptake depends on stem cell type, incubation time, particle concentration, and surface properties.

Histopathological evaluation of cutaneous malignant melanoma: A retrospective study.

Malignant melanoma is a melanocytic neoplasm with a steadily increasing incidence worldwide. In order to define a proper diagnostic protocol and to establish an accurate prognostic method for the disease, specific biomarkers are of notable importance. Their contribution is also significant in the treatment of melanoma for the improvement of newer and more targeted therapeutic approaches. To emphasize the importance of specific immune markers in the diagnosis of melanoma, immunohistochemical analysis was performed on 56 formalin-fixed paraffin-embedded cutaneous melanomas. Besides the traditional prognostic factors, depth of invasion and mitotic rate, the markers tested in the present study were S100 protein family, Melan A, Ki67 and HMB-45. The present results indicated that immunocytochemistry represents a valuable test in the diagnosis and treatment of malignant melanoma and each biomarker had different associations with the progression and prognosis of the disease. Patients with S100 expression were 4.83 times (95% CI=1.2-20.8) more likely to suffer a relapse, whereas patients with a Ki67 expression of >30% had a 5.41-fold higher risk (95% CI=1.3-22.0). The correlation between S100 and the Breslow depth was statistically significant (r-value: 0.43; P=0.027). In addition, the importance of a multidisciplinary team including a plastic surgeon, anatomopathologist and oncologist was highlighted.

Relevance of HLA gene polymorphisms in Romanian patients with chronic renal insufficiency undergoing renal transplantation.

BACKGROUND: Chronic renal insufficiency (CRI) is a global public health problem with a high incidence in the Romanian population. In this study, we aimed to investigate genomic HLA polymorphisms in Romanian patients with CRI waiting for kidney transplantation. To determine the existence of a potential strong link between certain HLA polymorphisms and CRI, we also looked at HLA specificity combinations within the same locus or even different loci, referring to randomly inherited allelic combinations rather than potential haplotypes. METHODS: A total of 2199 patients with CRI on the kidney transplantation waiting list were included. A total of 2786 healthy individuals were included as controls. Both patients and controls were assessed for both HLA I and class II genes. HLA genes were typed using the low-resolution method polymerase chain reaction sequence-specific primer. RESULTS: Certain class I and class II HLA allele groups, genotypes and haplotypes were significantly more frequent in patients with CRI than in the control individuals (eg B* 40 (p ≤ .001, pc ≤ .001), C* 12 (p ≤ .001, pc ≤ .001), DRB1*14 (p = .0022, pc = .04), C*12,- (p < .001, pc < .001), A*01-C*15 (p = .0003, pc = .03) and A*02-C*12 (p = .0005, pc = .0486)). CONCLUSIONS: HLA gene polymorphisms could be clinically relevant CRI-associated genetic profiles in Romanian patients with CRI.

Immunological and hormonal mechanisms in Alzheimer's disease.

Alzheimer's disease (AD) is a disorder which is today treated and approached at the crossroad of two medical specialties - psychiatry and neurology. The insidious onset which can often mimic depressive disorders or other type of psychiatric disorders, the behavioral changes, the paranoid thoughts usually send people to the psychiatrist, while the brain changes observed on magnetic resonance imaging (MRI) scans and other imaging techniques may indicate the need for neurological monitoring also. The complex symptomatology and progression of this dementia requires a multidisciplinary approach and recent studies focused on adding a third perspective: a metabolic one. The common findings regarding type 2 diabetes and AD made some researchers to informally name it "the third type diabetes". This mini review aims to highlight the mechanisms through which brain insulin resistance can lead to cognitive impairment and to make a short overview of the current findings which demonstrate why insulin may be a promising adjunctive treatment of Alzheimer's dementia, for certain patients.