Integration of Ultrasound in Image-Guided Adaptive Brachytherapy in Cancer of the Uterine Cervix.

Cervical cancer continues to be a public health concern, as it remains the second most common cancer despite screening programs. It is the third most common cause of cancer-related death for women, and the majority of cases happen in developing nations. The standard treatment for locally advanced cervical cancer involves the use of external beam radiation therapy, along with concurrent chemotherapy, followed by an image-guided adaptive brachytherapy (IGABT) boost. The five-year relative survival rate for European women diagnosed with cervical cancer was 62% between 2000 and 2007. Updated cervical cancer treatment guidelines based on IGABT have been developed by the Gynecological working group, which is composed of the Group Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology. The therapeutic strategy makes use of three-dimensional imaging, which can be tailored to the target volume and at-risk organs through the use of computed tomography or magnetic resonance imaging. Under anaesthesia, the brachytherapy implantation is carried out. Ultrasonography is utilised to assess the depth of the uterine cavity and to facilitate the dilation of the uterine canal during the application insertion. In this study, we examine data from the international literature regarding the application of ultrasound in cervical cancer brachytherapy.

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.

Laparoscopic Management of Multiple Liver, Omental, Mesenteric, Peritoneal, and Round Ligament Hydatid Cysts-A Rare Report of a Case and a Systematic Literature Review.

Hydatid cyst disease is a parasitic ailment with an endemic nature, predominantly affecting geographical areas with a tradition in animal husbandry. The most common localization of hydatid disease is in the liver (60%), followed by the lungs, with other organ localizations comprising less than 10%. The surgical approach to this condition can be carried out through open surgery or laparoscopy. The coexistence of hepatic and intraperitoneal hydatidosis often leads to the preference for open surgery. We performed a literature review aiming to retrieve data regarding demographic characteristics, clinical features, preoperative management, and surgical approach concerning these unusual localizations of hydatid disease. It was observed that the mesenteric localization frequently presented with acute abdominal pain (p = 0.038) and that the open approach was preferred in 85.71% of cases. Furthermore, an interdependence was identified between the localization of the cysts and the type of surgical approach (p = 0.001), with mesenteric localizations being approached through laparotomy and excision (p = 0.037), while omental localizations, due to the easier approach, benefited from laparoscopy with excision in 14.29% of cases. Overall, the laparoscopic approach was less frequently used, but its utilization resulted in a lower number of complications and faster recovery. Additionally, we present a rare case of hepatic and intra-abdominal hydatidosis, resolved exclusively through a laparoscopic approach, including a review of the literature for these uncommon localizations of hydatid disease. A 45-year-old patient diagnosed with multiple hydatid cysts, both hepatic and intraperitoneal, underwent surgical intervention with exploratory laparoscopy. Laparoscopic excision of peritoneal, epiploic, mesenteric cysts, and round ligament, along with laparoscopic inactivation, evacuation, and pericystectomy of hepatic hydatid cysts, was performed. The patient's recovery was uneventful, and she was reevaluated at 3 and 9 months without signs of recurrence. The association of hepatic hydatid cysts with multiple intra-abdominal localizations is not commonly encountered. The treatment of choice is surgical and is predominantly conducted through open surgery. The presented case is unique due to the exclusive laparoscopic approach in the management of mixed hepatic and intra-abdominal hydatidosis.

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.

Tips and Tricks for a Successful Literature Review as Part of Medical Career Development.

The literature review is a direct consequence of the increased volume of scientific information, becoming a necessity not only for the medical field. Such material, properly done, is of great use to any professional who wishes to keep abreast of the latest knowledge and concepts. The proposed goal is to help and guide resident doctors, doctoral students, and young researchers in understanding the concepts that are the basis of conducting a literature review and acquiring the generally accepted methodology for conducting it. The selection of information sources, accessing databases, the concept of peer-review, indexing and the impact factor are clearly presented as elements that cannot be neglected in the valorisation of scientific information sources. The structure of a literature review must consider the generally accepted format for such an article, with each chapter having its own importance. Depending on the quality and heterogeneity of the results obtained after analysing the collected data, the review can be structured narratively or systematically, the homogeneity of the results allowing the application of statistical study methods (meta-analysis). Although it seems difficult, conducting a literature review is easier and faster than developing an original study based on experimental or clinical scientific research. The literature review can be carried out in comfortable conditions, online, regardless of location and is a welcome support in the development of the professional and scientific career.

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.

Variability of Sentinel Lymph Node Location in Patients with Trunk Melanoma.

(1) Background: Melanoma is one of the most aggressive types of neoplasia, and the management of this pathology requires a correct staging, as well as a personalized modern oncological treatment. The main objective of the study is to determine the variability of the lymphatic drainage for patients with melanomas located on the trunk and, secondarily, to determine the features of individuals who underwent sentinel lymph node biopsy (SLNB) depending on the exact location on the trunk. (2) Methods: This retrospective, observational, single-center study included 62 cases of trunk melanoma operated between July 2019 and March 2023, in which SLNB was performed and a total of 84 lymph nodes were excised. (3) Results: Patients had a median age of 54.5 (33-78) years, with 58.1% being male; the melanomas had a median Breslow index of 2.3 (0.5-12.5) mm. Approximately 64.3% of the cohort had melanoma on the upper part of the trunk (54 cases) and 35.7% had it on the lower part (30 cases). The type of anesthesia chosen was general anesthesia in 53 cases and spinal anesthesia in 9 cases (85.5% vs. 14.5%, p < 0.001). The number of sentinel lymph nodes excised was 54 for melanomas located on the upper part of the trunk (8 cervical and 46 axillary) and 30 sentinel lymph nodes for melanomas of the lower part of the trunk (16 at the axillary level and 14 at the inguinal level). Out of the 54 LNs identified in patients with melanoma on the upper part of the trunk, 13 were positive, with a total of 12 positive lymph nodes (LNs) from the axillar basin, and only one from the cervical region. Additionally, the incidence of patients with a minimum of two identified sentinel lymph nodes was 32.2%, with a total of seven having LN involvement in two basins, and only one of these cases showed positivity for malignancy. (4) Conclusions: SLNBs were more frequent in the axillary region overall, and had more positive SLNs. Moreover, melanoma on the upper part of the trunk had a higher rate of positive SLNs compared to the lower part. Tumors located on the lower part of the truck had more positive SLNs in the axillary region than in the inguinal one.

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.

Transabdominal Preperitoneal Versus Lichtenstein Procedure for Inguinal Hernia Repair in Adults: A Comparative Evaluation of the Early Postoperative Pain and Outcomes.

Inguinal hernia repairs are one of the most common procedures in general surgery. In addition to classical open surgery, laparoscopic techniques, such as transabdominal preperitoneal (TAPP) and total extraperitoneal (TEP) hernia repair, have gained acceptance and are increasingly used for inguinal hernia repairs, and these three techniques are the only standards for inguinal hernia repairs. This study aimed to compare the results of inguinal hernia repairs in adult patients using the TAPP patch technique and Lichtenstein techniques regarding the level of pain perceived one day after surgery and the number of days of hospitalization. A two-year study was performed on 129 patients who underwent TAPP vs. 109 patients who underwent Liechtenstein hernia repair. Our results revealed statistical significance for both variables (Tpain(233) = -7.12, p< 0.001, d=2.92; Tdays of hospitalization(233) = -31.34, p< 0.001, d=4.01). TAPP is a safe method for inguinal hernia repairs, allowing quick recovery and less postoperative pain than the classical Liechtenstein technique.

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.

Laparogastroscopy-A Transgastric Laparoscopic Approach for Malignant Esophageal Stenosis.

This paper presents the laparogastroscopy procedure, a mini-invasive, palliative method as an alternative to gastrostomy to be recommended by gastroenterologists. Laparogastroscopic stenting with endoluminal transtumoral drilling solves the problem of oral nutrition in patients with unresectable esophageal cancer, avoiding percutaneous feeding. The results of this technique are presented in a retrospective analysis of a study group of 63 patients with advanced esophageal carcinoma admitted between January 2015 and December 2020 at Department of General Surgery of Emergency County Hospital Sibiu, Romania, in terms of post-operative morbidity and mortality. The type of stents used were Pezzer prostheses (48.6%), silicone prostheses (31.9%), and self-expanding metal stents (6.9%). Eight patients (12.7%) had fistulas (at admission to the clinic), which were successfully sealed. Post-operative dysphagia was absent in most patients and minimal in 16.6% of patients, so all patients could initiate oral feeding, improving their nutritional status. The average length of hospitalization for all patients was 9.22 ± 5.05 days. The most frequent local complications were restenosis (9.5%), stent displacement (7.9%), and bleeding (4.8%). The mean survival time was 10.75 ± 15.72 months. Laparogastroscopic stenting could be a valuable alternative in palliative esophageal cancer surgery, improving the quality of life and nutritional status in patients unsuitable for endoscopic stenting.

Novel Biomarkers Predictive of Diabetic Charcot Foot-An Overview of the Literature.

Background: Although Charcot diabetic foot (CDF) is a frequent complication of diabetic neuropathy, less is known about the possibility of its early prevention. Methods: A review of the original articles published in English, using the "biomarkers AND Charcot's foot" criterion, resulted in 33 articles from the PubMed database and seven articles from the Web of Science database. The five duplicates were eliminated, and two independent reviewers selected the most relevant articles, leaving a total of 21 articles. Results: The biomarkers identified are exhaustively described, related to the system of advanced glycation end products (AGEs) and their soluble receptors (sRAGE), inflammatory cascade, osteoclastogenesis, and, respectively, osteoblastic activity. Conclusions: This article highlights the importance of potential early identifiable biomarkers that can lead to microstructural changes in the affected bones.

Role of glutathione-S-transferase gene P1 in the diagnosis of prostate cancer in patients with 'grey level' prostate-specific antigen values.

Prostate cancer (PC) represents the second most frequent cancer diagnosis in men and, at the same time, is one of the top six causes of death worldwide. The aim of the present study was to evaluate the diagnostic value of glutathione-S-transferase gene P1 (GST-P1) in patients that fall within the 'grey area' of the prostate-specific antigen (PSA) values. A retrospective observational study on 80 patients with prostate abnormal volumes and PSA values in the range 4-10 ng/ml was performed. The prostate gland was extracted following transrectal ultrasonography, and GST-P1 gene expression was analysed. A histopathological examination was considered the gold standard for PC diagnosis. Among the 53 patients diagnosed with PC, 69.8% (n=37) were GST-P1-positive, whereas, among the 27 patients diagnosed with benign prostatic hyperplasia, 18.5% (n=5) were GST-P1-positive. The sensitivity for diagnosing PC in patients with PSA values between 4 and 10 ng/ml was 69.81%, and the specificity was 81.48%. The positive predictive value was 88.1% [95% confidence interval (CI), 74.37-96.02%] and the negative predictive value was 57.89% (95% CI, 40.82-73.69%). Collectively, these results show the potential of using GST-P1 gene expression in patients who are suspected of having PC, but where the PSA values are inconclusive.

Optimal Timing and Outcomes of Minimally Invasive Approach in Acute Biliary Pancreatitis.

BACKGROUND We analyzed the outcomes of early biliary decompression by a minimally invasive approach in acute biliary pancreatitis (ABP). MATERIAL AND METHODS A retrospective study was conducted on 143 patients with ABP who underwent biliary decompression by laparoscopic or endoscopic approach between January 2015 and March 2022. Data from the observation sheets and surgical protocols were analyzed in terms of demographic characteristics, clinical and paraclinical features at admission, comorbidities, therapeutic management, and outcomes. RESULTS The mean patient age was 62.3±11.4 years. Mild ABP had a higher frequency in men (75.5%) and urban areas (70.4%). The comorbidities associated with a higher risk of severe forms were diabetes mellitus (odds ratio [OR]: 11.250), chronic bronchopneumopathy (OR: 29.297), and ischemic coronary disease (OR: 2.784). The mean hospital stay was 7.6±3.8 days and was significantly higher in severe forms (10±2.4 days, P<0.001). The time from onset to presentation was significantly higher in severe vs mild forms (5.6 vs 1.8 days, P<0.001) and was associated with systemic and local complications. Creatinine over 2 mg/dL (OR: 4.821) and leukocytes >15 000/mmc at admission (OR: 3.533) were risk factors for systemic complications, while obesity was associated with increased local complications (OR: 5.179). None of the patients with an early presentation developed severe ABP. CONCLUSIONS Early biliary decompression, as soon as possible after onset, either by an endoscopic or minimally invasive approach, is a safe and effective procedure in ABP. The type of procedure and optimal timing should be individualized, according to the patient's local and general features.

A Real-World Study to Compare the Safety and Efficacy of Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir, with or without Ribavirin, in 587 Patients with Chronic Hepatitis C at the Fundeni Clinical Institute, Bucharest, Romania.

BACKGROUND In the European Union, a tablet with fixed doses of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir is an authorized treatment for patients with chronic hepatitis C virus (HCV) infection. Ribavirin is a broad-spectrum antiviral used in several treatment regimens for patients with HCV infection. This real-world study aimed to compare the safety and efficacy of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin, in 587 patients with chronic hepatitis C attending the Fundeni Clinical Institute, Bucharest, Romania. MATERIAL AND METHODS This is an observational prospective study including 315 patients with F4 degree of fibrosis and compensated cirrhosis, 185 patients with F3 fibrosis, and 83 patients with F2 fibrosis. Liver fibrosis was evaluated by liver biopsy or Fibromax. Efficacy was defined as undetectable HCV-RNA at 12 weeks after the end of treatment. In terms of safety, we monitored the development of adverse reactions, liver cytolysis, cholestasis, and hematologic disorders. RESULTS Of the 587 patients, 2 patients with B-cell lymphoma died during therapy. In total, 3/585 patients (0.51%) did not achieve sustained virologic response. Common adverse effects were nausea and asthenia (especially in patients with other medical treatments; P=0.03 and P=0.04, respectively) and anemia in patients who received ribavirin (P<0.01). None of the patients discontinued antiviral treatment. Patients with kidney transplant or end-stage kidney disease did not receive or discontinued ribavirin. CONCLUSIONS Ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin had an efficacy rate of over 99% in HCV genotype 1b infection. We report no serious adverse reactions.

A review of NTRK fusions in cancer.

The family of the neurotrophic tropomyosin kinase receptors (NTRK or TRK) is a part of the transmembrane tyrosine kinases responsible for neuronal development. The members of this receptor family are TRKA, TRKB and TRKC and they are encoded by the genes NTRK1, NTRK2 and NTRK3. Alterations of NTRK genes can induce carcinogenesis both in neurogenic and non-neurogenic cells. The prevalence of NTRK gene fusion is under 1% in solid tumors, but is highly encountered in rare tumors. The presence of NTRK 1 gene fusion is associated, in some types of neoplasia, with a favorable evolution, but the presence of NTRK 2 may be associated with a poor prognosis. The identification of cancer patients harboring NTRK gene fusions is constantly growing, especially with the advent of NTRK inhibitors. This has promisingly provided a rationale for personalized therapeutics that improved outcomes in settings with this signature.

Safety and Outcomes of Intravitreal Aflibercept in Diabetic Macular Edema - A Systematic Review.

BACKGROUND: Recent evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of ischemia and microvascular hyperpermeability leading to macular edema has brought anti-VEGF intravitreal therapy into the limelight. OBJECTIVE: We performed a systematic literature review focusing on the outcomes and safety of the intravitreal use of aflibercept in diabetic macular edema. METHODS: The studies documented cases with at least three consecutive intravitreal injections of aflibercept (IVA) repeated monthly with a follow-up period of at least one year. The outcomes were evaluated in terms of reported functional and anatomical improvement of the macula, as reflected by changes in visual acuity and macular thickness measured by Optical Coherence Tomography (OCT). In addition, for safety assessment, all reported local and general adverse effects were analyzed. RESULTS: All studies showed an overall significant anatomical and functional improvement. In patients with the 5 IVA monthly at the beginning of the therapy, the visual gain at 52 weeks varied widely between 5 and 18.9 EDRS letters, with a mean value of 9.48 letters. The higher gain was obtained in treatment naïve patients, with worse VA and increased CST at baseline. The lower gain was obtained in patients previously treated with anti- VEGF. Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events were not statistically different between the aflibercept group and the laser group. CONCLUSION: Intravitreal aflibercept therapy provides significant improvement in visual acuity and a good safety profile. Randomized studies are needed to document the optimal frequency of intravitreal injections for optimal treatment.