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DERM12345: A Large, Multisource Dermatoscopic Skin Lesion Dataset with 40 Subclasses
(Nature Research, 2024) Yılmaz, Abdurrahim; Yaşar, Şirin Pekcan; Gençoglan, Gülsüm; Temelkuran, Burak
Skin lesion datasets provide essential information for understanding various skin conditions and developing effective diagnostic tools. They aid the artificial intelligence-based early detection of skin cancer, facilitate treatment planning, and contribute to medical education and research. Published large datasets have partially coverage the subclassifications of the skin lesions. This limitation highlights the need for more expansive and varied datasets to reduce false predictions and help improve the failure analysis for skin lesions. This study presents a diverse dataset comprising 12,345 dermatoscopic images with 40 subclasses of skin lesions, collected in Turkiye, which comprises different skin types in the transition zone between Europe and Asia. Each subgroup contains high-resolution images and expert annotations, providing a strong and reliable basis for future research. The detailed analysis of each subgroup provided in this study facilitates targeted research endeavors and enhances the depth of understanding regarding the skin lesions. This dataset distinguishes itself through a diverse structure with its 5 super classes, 15 main classes, 40 subclasses and 12,345 high-resolution dermatoscopic images. © The Author(s) 2024.
Comparison of the Effects of Anaesthesia Methods Used in Caesarean Delivery on Neonatal Cerebral and Renal Oxygenation: A Randomised Controlled Trial
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Arslan, Ülkü; Kavrut Öztürk, Nilgün; Kavaklı, Ali Sait; Dağdelen, Hatice Özge
Background: During a newborn’s adaptation to extrauterine life, many changes take place that are influenced by various factors. The type of delivery and anaesthesia strategy utilised during labour can modify these adaptive modifications. In this regard, this study was designed to compare the effects of general and spinal anaesthesia on cerebral and renal oxygenation after elective caesarean deliveries. Methods: This randomised controlled study comprised sixty parturient women who were over 18 years old and had a gestational age between 37 and 41 weeks. All participants had an ASA (American Society of Anesthesiologists) classification of II. Neonatal cerebral (CrSO2) and renal (RrSO2) regional oxygen saturations were assessed using near-infrared spectroscopy. Additionally, the 1st–5th min Apgar scores, preductal and postductal peripheral oxygen saturation (SpO2), and perfusion index were recorded in both the general anaesthesia and spinal anaesthesia groups. Results: There was no statistically significant difference between the two groups in terms of CrSO2 or RrSO2 values. The values of CrSO2 and RrSO2 in both groups showed a significant rise from the 10th to the 15th min, respectively. Conclusions: General and spinal anaesthesia techniques used for cesarean delivery have similar effects on neonatal cerebral and renal oxygenation. © 2024 by the authors.
The effect of ultrasound-guided erector spinae plane block on postoperative opioid consumption and respiratory recovery in laparoscopic sleeve gastrectomy: a randomized controlled study
(Springer, 2024) Karaveli, Arzu; Kaplan, Serdar; Kavaklı, Ali Sait; Koşar, Mehmet Nuri; Mayir, Burhan
Background The aim of this prospective, randomized, controlled study was to evaluate the effect of ultrasound (US)-guided bilateral erector spinae plane (ESP) block on postoperative opioid consumption and respiratory recovery in patients with obesity undergoing laparoscopic sleeve gastrectomy (LSG). Methods The study was conducted on 40 patients scheduled for LSG. The patients were randomly allocated into either the ESP block group or the control group. The US-guided bilateral ESP block was performed preoperatively. The control group received no intervention. Results Postoperative median [IQR] tramadol consumption was significantly lower in the ESP block group [150.0 [100-200] mg vs 450.0 [400-500] mg, p < 0.0001]. Postoperative spirometric variables were significantly impaired in both groups, compared with preoperative variables (p < 0.0001). Intraoperative median [IQR] fentanyl consumption was 200.0 [200-200] mu g in the ESP block group, and 350.0 [300-400] mu g in the control group (p < 0.0001). Postoperative mean pain scores at rest and during movement were significantly lower in the ESP block group, at all time points (p < 0.05). In terms of mean arterial PH, Horowitz ratio, and PaCO2, there was no statistically significant difference between the groups (p > 0.05). None of the patients experienced postoperative respiratory adverse events and/or block-related complications. Conclusions US-guided bilateral ESP block significantly reduced both intraoperative and postoperative analgesic consumptions and provided effective postoperative pain control for patients with obesity undergoing bariatric surgery. Following bariatric surgery, all patients' postoperative pulmonary functions deteriorated. The effect of US-guided bilateral ESP block on postoperative respiratory recovery could not be clearly demonstrated. Randomized controlled studies with a larger patient population are necessary.
Machine Learning May Be an Alternative to BIPSS in the Differential Diagnosis of ACTH-dependent Cushing Syndrome
(Endocrine Society, 2025) Demir, Ahmet Numan; Ayata, Değer; Öz, Ahmet; Sulu, Cem; Kara, Zehra; Şahin, Serdar; Özaydın, Dilan; Korkmazer, Bora; Arslan, Serdar; Kızılkılıç, Osman; Çiftçi, Sema; Çelik, Özlem; Özkaya, Hande Mefkure; Tanrıöver, Necmettin; Gazioğlu, Nurperi; Kadıoğlu, Pınar
Context: Artificial intelligence research in the field of neuroendocrinology has accelerated. It is possible to develop noninvasive, easy-to-use and cost-effective procedures that can replace invasive procedures for the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) by artificial intelligence. Objective: This study aimed to develop machine-learning (ML) algorithms for the differential diagnosis of ACTH-dependent CS based on biochemical and radiological features. Methods: Logistic regression algorithms were used for ML, and the area under the receiver operating characteristics curve was used to measure performance. We used Shapley contributed comments (SHAP) values, which help explain the results of the ML models to identify the meaning of each feature and facilitate interpretation. Results: A total of 106 patients, 80 with Cushing disease (CD) and 26 with ectopic ACTH syndrome (EAS), were enrolled in the study. The ML task was created to classify patients with ACTH-dependent CS into CD and EAS. The average AUROC value obtained in the cross-validation of the logistic regression model created for the classification task was 0.850. The diagnostic accuracy of the algorithm was 86%. The SHAP values indicated that the most important determinants for the model were the 2-day 2-mg dexamethasone suppression test, greater than 50% suppression in the 8-mg high-dose dexamethasone test, late-night salivary cortisol, and the diameter of the pituitary adenoma. We have also made our algorithm available to all clinicians via a user-friendly interface. Conclusion: ML algorithms have the potential to serve as an alternative decision-support tool to invasive procedures in the differential diagnosis of ACTH-dependent CS. © The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved
Efficacy of omentopexy on complications of laparoscopic sleeve gastrectomy
(Springer, 2024) Kara, Yalçın Burak; Özel, Yahya; Yardımcı, Samet
Background Laparoscopic sleeve gastrectomy (LSG) is a commonly performed type of bariatric surgery. Early complications of LSG include bleeding, leakage, pulmonary embolism, and surgical site infections. Most surgeons try to implement preventive methods, such as omentopexy. Staple line-imbrication, which has a difficult learning curve, often prevents complications. This study aimed to evaluate the effect of omentopexy on patients with imbricated LSG.Material and Methods The study applied a retrospective data analysis design to patients who underwent LSG between 2020 and 2023. All patients' staple lines were imbricated, and patients were then divided into two groups: omentopexy group and control group. Patients' demographic features, such as age, gender, height, weight, body mass index(BMI), bleeding, leakage, and reoperations, were recorded and examined retrospectively.Results A total of 1356 patients were included in the study (540 in omentopexy, 816 in control), of which the mean age was 37.9 +/- 10.5 years, 82.3% were women, and mean BMI was 40.9 +/- 5.8 kg/m2. The mean bleeding rate was 1.0% (1.3-0.7%), the mean leakage rate was 0.2% (0.2-0.2%, respectively), and the mean reoperation rate was 0.6% (0.7% and 0.5%, respectively). No statistically significant differences were observed.Conclusion Omentopexy is a technique that is widely used to prevent staple line complications. According to our study, omentopexy applied to an imbricated stapler line increased the operation time but did not affect bleeding or leakage ratios. This is the first study to evaluate the effect of omentopexy on imbricated staple lines. The findings of the study indicate that omentopexy has no additional benefit on early complications when using staple-line imbrication.
Emerging therapies against Naegleria fowleri
(Taylor & francis ltd, 2024) Siddiqui, Ruqaiyyah; Lloyd, David; Alharbi, Ahmad M.; Khan, Naveed Ahmed
Introduction Naegleria fowleri is a free-living protist pathogen. Given the opportunity, it can produce infection of the central nervous system. It is distressing that the brain-eating amoebae, Naegleria fowleri remains one of the lethal parasites resulting almost always in death, despite advances in antimicrobial chemotherapy and supportive care. Areas covered The overall aim is to present a timely review of our current understanding of emerging therapies and priorities. By searching bibliographic databases (PubMed) for the available peer-reviewed research literature, herein, we discuss current advances, challenges and opportunities pertinent in the development of therapeutic interventions. Expert opinion The prospect of exploring repurposed drugs in combination with nanotechnology and a theranostic approach to concurrently achieve diagnosis and drug delivery will offer promise in the rational development of effective therapies to counter N. folweri-associated fatal brain infections.
Evaluation of the effect of morphological structure on dilatational tracheostomy interference location and complications with ultrasonography and fiberoptic bronchoscopy
(MDPI, 2024) Bulut, Esin; Yıldız, Ülkü Arslan; Cengiz, Melike; Yılmaz, Murat; Kavaklı, Ali Sait; Arıcı, Ayşe Gülbin; Öztürk, Nihal
Background: Percutaneous dilatational tracheostomy (PDT) is the most commonly performed minimally invasive intensive care unit procedure worldwide. Methods: This study evaluated the percentage of consistency between the entry site observed with fiberoptic bronchoscopy (FOB) and the prediction for the PDT level based on pre-procedural ultrasonography (USG) in PDT procedures performed using the forceps dilatation method. The effect of morphological features on intervention sites was also investigated. Complications that occurred during and after the procedure, as well as the duration, site, and quantity of the procedures, were recorded. Results: Data obtained from a total of 91 patients were analyzed. In 57 patients (62.6%), the USG-estimated tracheal puncture level was consistent with the intercartilaginous space observed by FOB, while in 34 patients (37.4%), there was a discrepancy between these two methods. According to Bland Altman, the agreement between the tracheal spaces determined by USG and FOB was close. Regression formulas for PDT procedures defining the intercartilaginous puncture level based on morphologic measurements of the patients were created. The most common complication related to PDT was cartilage fracture (17.6%), which was proven to be predicted with maximum relevance by punctured tracheal level, neck extension limitation, and procedure duration. Conclusions: In PDT procedures using the forceps dilatation method, the prediction of the PDT intervention level based on pre-procedural USG was considerably in accordance with the entry site observed by FOB. The intercartilaginous puncture level could be estimated based on morphological measurements.
Evaluating YouTube Videos With Prophylactic Mastectomy Content in Terms of Their Quality and Reliability
(2025) Altıntaş, Tansu; Bilgi Kırmacı, Mehlika
Aim: Purpose of this study is to investigate the quality and reliability of YouTube video contents on prophylactic mastectomy. Material and Methods: The search terms "prophylactic mastectomy," "prophylactic mastectomy surgery," "preventive surgery for breast cancer," "risk-reducing mastectomy," and "prophylactic mastectomy and breast reconstruction" were searched on YouTube. The uploader, video content, length (seconds), upload date, number of days since upload date, number of views, number of comments, and likes were recorded and evaluated. Finally, the videos included in the study were evaluated using modified Quality Criteria for Consumer Health Information (DISCERN) and Global Quality Scale (GQS). Results: The total number of views of the 50 videos reviewed in the study was found as 3.674.469. The mean DISCERN score of the two observers was calculated as 3.35 ± 1, and the videos were found to be of medium reliability. The mean GQS score of all videos was 3.39 ± 0.9 and the videos were of medium quality. The researchers gave 1-2 points (misleading) to 7 (14%) videos, 3 points (somewhat helpful) to 20 (40%) videos, 4 points (beneficial) to 16 (32%) videos, and 5 points (excellent) to 7 (14%) videos. Conclusion: In our study, we found that the videos uploaded by doctors were of good quality, the videos uploaded by health channels were of medium quality, and the videos uploaded by patients were of poor quality and misleading. The videos with health contents should be evaluated by the relevant specialists, and only useful videos should be broadcast. Copyright © 2025 Tansu Altintas and Mehlika Bilgi Kirmaci. The Breast Journal published by John Wiley & Sons Ltd.
External Auditory Canal Transillumination-Guided Middle Fossa Approaches: An Anatomical Feasibility Study
(Lippincott Williams and Wilkins, 2025) Şahin, Mustafa; Güngör, Abuzer; Doǧruel, Yücel; Luzzi, Sabino; Yılmaz, Adem; Türe, Uğur
BACKGROUND AND OBJECTIVES: The middle fossa approaches are tremendously versatile for treating small vestibular schwannomas, selected petroclival meningiomas, midbasilar trunk aneurysms, and lesions of the petrous bone. Our aim was to localize the internal acoustic canal and safely drill the petrous apex with these approaches. This study demonstrates a new method to locate the internal acoustic canal during surgery in the middle fossa. METHODS: The microsurgical anatomy of the middle fossa floor was studied in 11 formalin-fixed and silicone-injected cadaveric heads. Extradural dissection of the skull base was completed from the posterior to the anterior side. A zero-degree rigid endoscope was inserted perpendicularly into the external auditory canal. The light beam was first directed through the tympanic membrane, avoiding injury to the tympanic membrane. The room lights were dimmed to provide a clearer view of the transilluminated bony area. Drilling was performed with transillumination guidance. RESULTS: The transilluminated area included the tympanic and mastoid tegmen up to the arcuate eminence. The nonilluminated area was bounded posteriorly by the arcuate eminence, laterally by the greater superficial petrosal nerve, and posteromedially by the petrous ridge. In all specimens, drilling the transition line between the Kawase triangle and the transilluminated area unroofed the internal auditory canal (IAC). No transillumination of the carotid canal was seen after anterior petrosectomy in any of the specimens. The entire contents of the IAC were preserved in both anterior petrosectomy and unroofing of the IAC. CONCLUSION: In this anatomical study, transillumination of the external auditory canal proved to be feasible, accurate, and safe in guiding the middle fossa approaches. The ease of implementation and cost-effectiveness of the technique may suggest a possible application in operative scenarios. © Congress of Neurological Surgeons 2025. All rights reserved.
Medical management of chronic subdural hematoma with low-dose hydrocortisone: a case series
(Springer Science and Business Media Deutschland GmbH, 2024) Gürses, Muhammet Enes; Ülgen, Meriç; Gökalp, Elif; Gecici, Neslihan Nisa; Güngör, Abuzer; Türe, Hatice; Türe, Uğur
Chronic subdural hematomas (cSDH) are often managed with a burr-hole craniostomy and drainage, but surgery is associated with elevated mortality, morbidity, and recurrence. Despite reports of steroid use for such patients, its efficacy and feasibility are still debated. We present our patient series treated with low-dose hydrocortisone. We retrospectively reviewed data from patients treated with hydrocortisone between 2017 and 2023. Demographics, clinical and radiological data were collected. Of 27 patients identified, nine required a burr-hole craniotomy for an average volume of 120.23 cm3, average midline shift of 9 mm, and neurological deficits. Eighteen met the criteria for inclusion. The mean age was 78.5 years; 13 were male. None had severe symptoms requiring urgent intervention. Except for one with a Karnofsky Performance Scale score of 70, all could maintain normal activity before treatment. The mean baseline volume was 52.6 cm3. Midline shift, present in six, averaged 6.8 mm. Patients underwent treatment for an average of 5.15 months. Nine had complete resolution within 3 months, while nine required longer treatment, including one who needed 9 months for a re-bleed after a fall. Paired t-tests indicated significant reductions in hematoma volumes at the second week (p = 0.01), first month (p < 0.0001), and third month (p < 0.0001) of treatment. No complications occurred and the post-treatment Karnofsky scores ranged from 90 to 100. Treatment for cSDH should be tailored to the patient. Low-dose hydrocortisone is safe and effective in asymptomatic patients, those with mild to moderate symptoms, and those who are either unsuitable for or decline surgical intervention. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models
(American association advancement science, 2024) Demirlenk, Yusuf M.; Albadawi, Hassan; Zhang, Zefu; Atar, Dila; Çevik, Enes; Keum, Hyeongseop; Kim, Jinjoo; Rehman, Suliman; Gündüz, Şeyda; Graf, Erin; Mayer, Joseph L.; Dos Santos, Pedro R.; Oklu, Rahmi
Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.
Can We Predict Gastric Leaks after Laparoscopic Sleeve Gastrectomy by Evaluating the Complete Blood Count on Postoperative Day 1?
(Lippincott Williams and Wilkins, 2024) Seyit, Hakan; Gökçal, Fahri; Alış, Halil
Introduction: We assessed whether postoperative day-1 (POD-1) complete blood count (CBC) test parameters, including red cell distribution width (RDW), mean platelet volume (MPV), plateletcrit (PCT), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), could identify patients with gastric leaks after laparoscopic sleeve gastrectomy (LSG). Methods: Patients with postoperative gastric leaks (n=36) and patients with no complications who were selected by age-sex-BMI matching (n=254) were included in the study. The levels of RDW, MPW, PCT, PLR, and NLR were compared between groups in univariate analyses. Receiver operating characteristic (ROC) curve analysis was run for CBC parameters with a P-value<0.05 in univariate analyses. The area under the curve (AUC) was evaluated, and a cutoff value was determined. Sensitivity, specificity, likelihood ratio (LR), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Results: The level of PCT was significantly lower, while levels of PLR and NLR were significantly higher in patients with postoperative gastric leaks as compared with those without (P<0.05). The AUC of both PCT and PLR was <0.750, while the AUC of NLR was 0.911. NLR cutoff at 3.6 yielded 80% sensitivity, 92% specificity, and an LR of 10. In the study cohort, PPV of 59%, NPV of 97%, and an accuracy of 90% were found. Conclusions: Our results suggest that NLR at POD-1, with a cutoff value of 3.6, is a useful indicator of postoperative gastric leak who underwent LSG. We recommend the use of this easily calculated parameter in clinical practice. © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Human adapted prosomeric model: a future for brainstem tumor classification
(Elsevier, 2024) Munoz-Gualan, Alberth Patricio; Güngör, Abuzer; Cezayirli, Phillip Cem; Rahmanov, Serdar; Gürses, Muhammet Enes; Puelles, Luis; Türe, Uğur
This study reevaluates the conventional understanding of midbrain anatomy and neuroanatomical nomenclature in the context of recent genetic and anatomical discoveries. The authors assert that the midbrain should be viewed as an integral part of the forebrain due to shared genetic determinants and evolutionary lineage. The isthmo-mesencephalic boundary is recognized as a significant organizer for both the caudal midbrain and the isthmo-cerebellar area. The article adopts the prosomeric model, redefining the whole brain as neuromeres, offering a more precise depiction of brain development, including processes like proliferation, neurogenesis, cell migration, and differentiation. This shift in understanding challenges traditional definitions of the midbrain based on external brain morphology. The study also delves into the historical context of neuroanatomical models, including the columnar model proposed by Herrick in 1910, which has influenced our understanding of brain structure. Furthermore, the study has clinical implications, affecting neuroanatomy, neurodevelopmental studies, and the diagnosis and treatment of brain disorders. It emphasizes the need to integrate molecular research into human neuroanatomical studies and advocates for updating neuroanatomical terminology to reflect modern genetic and molecular insights. The authors propose two key revisions. First, we suggest reclassifying the isthmo-cerebellar prepontine region as part of the hindbrain, due to its role in cerebellar development and distinct location caudal to the genetically-defined midbrain. Second, we recommend redefining the anterior boundary of the genetically-defined midbrain to align with genetic markers. In conclusion, the authors highlight the importance of harmonizing neuroanatomical nomenclature with current scientific knowledge, promoting a more precise and informed understanding of brain structure, which is crucial for both research and clinical applications related to the human brain.
Peak force of insertion during ureteral access sheath placement in an ex-vivo experimental model with different commercially available access sheaths
(Elsevier, 2024) Ergül, Rıfat Burak; Butticè, Salvatore; Yitgin, Yasin; Günver, Mehmet Güven; Özcan, Faruk; Nane, İsmet; Traxer, Olivier; Tefik, Tzevat
Objective: To measure the force necessary to win the resistance during insertion of ureteral access sheaths (UAS) in an experimental homemade model and to compare the peak force of insertion (PFOI) of different commercially available UASs. Methods: Three investigators (2 novice and 1 expert) inserted the UASs into 2 different adapters with diameters of 10 Fr and 8 Fr. The force of insertion was continuously measured with a digital force gauge connected to the UAS during each insertion. Four different brands of UAS with different diameters, totally 11 different UASs were used for the experiment. The PFOI of each UAS was compared among each other and adapter diameters. Results: The mean PFOI in adapters 1 and 2 were 1.85 N and 5.32 N, respectively. All of the mean PFOIs were significantly lower in adapter 1 compared to adapter 2, regardless of the novice vs expert surgeons and the UASs. (P <.001) In adapter 1, the mean PFOI was lowest with the UAS-1 and highest with the UAS-8. In adapter 2, the mean PFOI was lowest with the UAS-3 and highest with the UAS-9. For adapters 1 and 2, no statistical difference was found when comparing an expert and the 2 novice surgeons. Conclusion: The PFOI during UAS placement is not solely correlated with UAS thickness and adapter diameters. Other factors such as hydrophilic coating, UAS flexibility, inner dilator properties, UAS smoothness, and the actual measured external diameter of UASs should be taken into consideration. The clinical relevance and ureteral injury risk of the UAS PFOI need to be studied.
Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial
(Nature portfolio, 2024) Powles, Thomas; Chang, Yen-Hwa; Yamamoto, Yoshiaki; Munoz, Jose; Reyes-Cosmelli, Felipe; Peer, Avivit; Cohen, Graham; Yu, Evan Y.; Lorch, Anja; Bavle, Abhishek; Moreno, Blanca Homet; Markensohn, Julia; Edmondson, Mackenzie; Chen, Cai; Cristescu, Razvan; Pena, Carol; Lunceford, Jared; Gündüz, Şeyda
Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance. To identify potential biomarkers of response, we retrospectively evaluated the association of pre- and posttreatment ctDNA with clinical outcomes in a subset of patients who received pembrolizumab (n = 130) or chemotherapy (n = 130) in KEYNOTE-361. Baseline ctDNA was associated with best overall response (BOR; P = 0.009), progression-free survival (P < 0.001) and overall survival (OS; P < 0.001) for pembrolizumab but not for chemotherapy (all; P > 0.05). Chemotherapy induced larger ctDNA decreases from baseline to treatment cycle 2 than pembrolizumab; however, change with pembrolizumab (n = 87) was more associated with BOR (P = 4.39 x 10(-5)) and OS (P = 7.07 x 10(-5)) than chemotherapy (n = 102; BOR: P = 1.01 x 10(-4); OS: P = 0.018). Tumor tissue-informed versions of ctDNA change metrics were most associated with clinical outcomes but did not show a statistically significant independent value for explaining OS beyond radiographic change by RECIST v.1.1 when jointly modeled (pembrolizumab P = 0.364; chemotherapy P = 0.823). These results suggest distinct patterns in early ctDNA changes with immunotherapy and chemotherapy and differences in their association with long-term outcomes, which provide preliminary insights into the utility of liquid biopsies for treatment monitoring in metastatic urothelial cancer. Clinical trial registration: NCT02853305.
Phosphonium chloride-based deep eutectic solvents inhibit pathogenic Acanthamoeba castellanii belonging to the T4 genotype
(Springer, 2024) Akbar, Noor; Khan, Amir Sada; Siddiqui, Ruqaiyyah; Ibrahim, Taleb Hassan; Khamis, Mustafa I.; Alawfi, Bader S.; Al-ahmadi, Bassam M.; Khan, Naveed Ahmed
Herein, we investigated the anti-amoebic activity of phosphonium-chloride-based deep eutectic solvents against pathogenic Acanthamoeba castellanii of the T4 genotype. Deep eutectic solvents are ionic fluids composed of two or three substances, capable of self-association to form a eutectic mixture with a melting point lower than each substance. In this study, three distinct hydrophobic deep eutectic solvents were formulated, employing trihexyltetradecylphosphonium chloride as the hydrogen bond acceptor and aspirin, dodecanoic acid, and 4-tert-butylbenzoic acid as the hydrogen bond donors. Subsequently, all three deep eutectic solvents, denoted as DES1, DES2, DES3 formulations, underwent investigations comprising amoebicidal, adhesion, excystation, cytotoxicity, and cytopathogenicity assays. The findings revealed that DES2 was the most potent anti-amoebic agent, with a 94% elimination rate against the amoebae within 24 h at 30 degrees C. Adhesion assays revealed that deep eutectic solvents hindered amoebae adhesion to human brain endothelial cells, with DES2 exhibiting 88% reduction of adhesion. Notably, DES3 exhibited remarkable anti-excystation properties, preventing 94% of cysts from reverting to trophozoites. In cytopathogenicity experiments, deep eutectic solvent formulations and dodecanoic acid alone reduced amoebae-induced human brain endothelial cell death, with DES2 showing the highest effects. Lactate dehydrogenase assays revealed the minimal cytotoxicity of the tested deep eutectic solvents, with the exception of trihexyltetradecylphosphonium chloride, which exhibited 35% endothelial cell damage. These findings underscore the potential of specific deep eutectic solvents in combating pathogenic Acanthamoeba, presenting promising avenues for further research and development against free-living amoebae.
Graft Paste to Tackle Nasal Dorsal Irregularities: A Comparative, Prospective, Double Blinded Study
(Springer, 2024) Zuhour, Moath; Ismayilzade, Majid; İnce, Bilsev
Background: Preventing dorsal irregularities, especially in noses with high humps, is still a challenging process. Classic treatment with diced grafts may itself result in dorsal irregularities. Objectives: It was aimed to investigate the effectiveness of graft paste in preventing and correcting the dorsal irregularities. Methods: A total of 60 patients were included in this study. While diced cartilage was used in group A, graft paste was used in group B. Hump heights and collected graft volume were recorded. To evaluate aesthetic outcomes, preoperative and postoperative ROE questionnaire and postoperative physical examination were performed. Results: Although the hump height of group A (5.9 ± 1.02 mm) was greater than that of group B (5.6 ± 1.15 mm), the collected graft volume in group B was statistically higher (P < 05) (0.26 ± 0.05 cc and 0.16 ± 0.13 cc, respectively). Group B showed higher postoperative ROE scores (84.67 ± 8.9) compared to group A (80.15 ± 7.6). While the mean physical examination score for group A was 1.12 ± 0.96, this value was 0.62 ± 0.71 for group B (P < 05). None of the patients of group B had visible irregularities, but two patients of group A had. Conclusion: The graft paste is a safe and reliable method to prevent and treat the dorsal irregularities. The paste has a soft and cohesive structure which makes it to ideal for filling the irregularities and the dead spaces on the surface of the dorsum. Graft paste was associated with a better aesthetic outcome compared to diced cartilage. Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266. © Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2024.
Next generation imidazothiazole and imidazooxazole derivatives as potential drugs against brain-eating amoebae
(Springer, 2024) Akbar, Noor; Siddiqui, Ruqaiyyah; El-Gamal, Mohammed I.; Khan, Naveed Ahmed; Zaraei, Seyed-Omar; Saeed, Balsam Qubais; Alharbi, Ahmad M.; Dash, Nihar Ranjan
Managing primary amoebic meningoencephalitis, induced by Naegleria fowleri poses a complex medical challenge. There is currently no specific anti-amoebic drug that has proven effectiveness against N. fowleri infection. Ongoing research endeavours are dedicated to uncovering innovative treatment strategies, including the utilization of drugs and immune modulators targeting Naegleria infection. In this study, we explored the potential of imidazo[2,1-b]thiazole and imidazooxazole derivatives that incorporate sulfonate and sulfamate groups as agents with anti-amoebic properties against N. fowleri. We assessed several synthesized compounds (1f, 1m, 1q, 1s, and 1t) for their efficacy in eliminating amoebae, their impact on cytotoxicity, and their influence on the damage caused to human cerebral microvascular endothelial (HBEC-5i) cells when exposed to the N. fowleri (ATCC 30174) strain. The outcomes revealed that, among the five compounds under examination, 1m, 1q, and 1t demonstrated notable anti-parasitic effects against N. fowleri (P <= 0.05). Compound 1t exhibited the highest anti-parasitic activity, reducing N. fowleri population by 80%. Additionally, three compounds, 1m, 1q, and 1t, significantly mitigated the damage inflicted on host cells by N. fowleri. However, the results of cytotoxicity analysis indicated that while 1m and 1q had minimal cytotoxic effects on endothelial cells, compound 1t caused moderate cytotoxicity (34%). Consequently, we conclude that imidazo[2,1-b]thiazole and imidazooxazole derivatives containing sulfonate and sulfamate groups exhibit a marked capacity to eliminate amoebae viability while causing limited toxicity to human cells. In aggregate, these findings hold promise that could potentially evolve into novel therapeutic options for treating N. fowleri infection
Neglected tracts of the brainstem: transverse peduncular tract of Gudden and taenia pontis
(American association of neurological surgeons, 2024) Rahmanov, Serdar; Güngör, Abuzer; Gülsuna, Beste; Munoz-Gualan, Alberth Patricio
OBJECTIVE The anatomy and function of the brainstem have fascinated scientists for centuries; however, the brain- stem remains one of the least studied regions of the human brain. As the authors delved into studying this structure, they observed a growing tendency to forget or neglect previously identified structures. The aim of this study was to describe two such structures: the transverse peduncular tract, also known as the Gudden tract, and the taenia pontis. The authors analyzed the potential effects of neglecting these structures during brainstem surgery and the implications for clinical practice. METHODS After removal of the arachnoid and vascular structures, 20 human brainstem specimens were frozen and stored at -16 degrees C degrees C for 2 weeks, according to the method described by Klingler. The specimens were then thawed and dissected with microsurgical techniques. The results of microsurgical fiber dissection at each step were photographed. RESULTS This study revealed two previously neglected or forgotten structures within the brainstem. The first is the transverse peduncular tract of Gudden, which arises from the brachium of the superior colliculus. This tract follows an arcuate course along the lateral and ventral surfaces of the midbrain, perpendicular to the cerebral peduncle, and terminates in the nuclei of the transverse peduncular tract within the interpeduncular fossa. The second structure is the taenia pontis, which originates contralaterally in the interpeduncular fossa. It becomes visible at the level of the pontomesencephalic sulcus and extends to the base of the lateral mesencephalic sulcus, where it divides into several thin bundles. Along the interpeduncular sulcus, between the superior and middle cerebellar peduncles, it reaches the parabrachial recess and enters the cerebellum. CONCLUSIONS Recently, with increasing understanding and expertise in brainstem research, surgical approaches to this area have become more common, emphasizing the importance of a detailed knowledge of the brainstem. The two structures mentioned in this paper are described in history books and were widely studied in the 19th century but have not been mentioned in modern literature. The authors propose that a deeper understanding of these structures may prove valuable in neurosurgical practice and help reduce patient comorbidity.
Evaluation of the effects of ectopic replantation on amputate survival in the management of crush traumatic amputations in rats: An experimental study
(Turkish Association of Trauma and Emergency Surgery, 2024) Kendir, Münür Selçuk; İnce, Bilsev; İsmayılzade, Majid; Baycar, Zikrullah; Nurşen, Hayri Ahmet Burak; Dadacı, Mehmet
BACKGROUND: This controlled experimental study aimed to compare ectopic replantation with other replantation techniques in a rat model of crush amputations. It also assessed the impact of different replantation methods on the viability of amputates. METHODS: Forty male Wistar albino rats were divided into four groups. Groin flaps served as the amputation model. Group 1 underwent guillotine-style amputation followed by orthotopic replantation, Group 2 experienced crush-type amputation and orthotopic replantation, Group 3 had crush-type amputation and orthotopic replantation with a vein graft, and Group 4 underwent crush-type amputation followed by ectopic replantation. Flap viability and perfusion rates were assessed on day 3 using an infrared perfusion assessment system. The ratio of viable area to total flap area and thrombus formation in the pedicle vessels were evaluated on day 7. RESULTS: Infrared evaluations on day 3 post-replantation revealed flap perfusion percentages of 73.5% in Group 1, 11.1% in Group 2, 65% in Group 3, and 64.1% in Group 4. Statistical analysis indicated that Group 1 exhibited the highest perfusion rates, while Group 2 showed the lowest. No differences were observed between Groups 3 and 4. On the seventh day, the average surviving flap areas were found to be 74.6% in Group 1, 2.5% in Group 2, 64.5% in Group 3, and 64% in Group 4. Statistically, Group 1 exhibited the best outcomes, while Group 2 had the poorest, with no differences between Groups 3 and 4. Additionally, thrombus formation was observed in the vessels of two animals in Group 1, nine in Group 2, and three each in Groups 3 and 4. Significant statistical differences were noted among the groups. CONCLUSION: The results indicate that ectopic replantation and replantation with a vein graft are equally effective. The preferred method for crush-type replantations may depend on the patient’s and the amputated limb’s conditions. In crush-type amputations, we recommend vein graft repair if the patient’s overall condition supports replantation and if crushed segments can be debrided without excessive shortening of the amputated part. If these conditions are not met, temporary ectopic replantation is advised to preserve the amputated limb. © 2024, Turkish Association of Trauma and Emergency Surgery. All rights reserved.

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