Aorto caval fistulas.

BACKGROUND: The purpose of this paper is to examine and assess the outcomes following open repair in 39 patients who experienced aorto-caval fistula (ACF) resulting from the spontaneous rupture of an abdominal aortic aneurysm (AAA). METHODS: We reviewed the clinical records of all patients surgically treated with open repair for ACF at the Clinic for Vascular and Endovascular Surgery of the Serbian Clinical Center in Belgrade, Serbia, from January 2012 to February 2023. All of the patients in this series were consecutive and had aorto-caval fistula from AAA. No patients were excluded from the procedure due to the life-threatening nature of the state. A follow-up assessment was performed during the follow-up examination or by telephone interview with the patient or a family member. RESULTS: All patients were male, with mean age 67.4±8.3 years (range: 52-83 years). The 30-day mortality rate in our cohort was 35.9%, with three (7.7%) intraoperative deaths, and 11 deaths in the postoperative period (28.2%). A total of 25 patients out of 39 (64.1%) in the original cohort have survived the surgery and the postoperative period and were followed-up for a total of 67.1 person-years. The mean follow-up was 3.7±2.2 years (range 0.25-8.4 years). Two patients (8.0%) died during the follow-up, 16 patients (64.0%) survived, and seven (28.0%) were lost to follow-up. The long-term mortality rate in the cohort that survived the postoperative period was 3.0/100 person-years. CONCLUSIONS: ACF caused by spontaneous AAA rupture into the inferior caval vein or iliac veins is a relatively rare, life-threatening condition which requires prompt treatment. An exact preoperative diagnosis is essential for perioperative strategy. As the comparison of our results with the results from contemporary literature indicates, wherever possible endovascular repair should be considered since it results might be superior to open repair.

Corticosteroid Injection With and Without Local Anesthetic for the Treatment of Trigger Finger: A Randomized Clinical Trial.

PURPOSE: This study aimed to report pain during and following injection for trigger finger as well as failure to resolve triggering. We hypothesized that a corticosteroid injection alone would be equally or less painful compared with the standard combination of corticosteroid and lidocaine for the treatment of trigger fingers, and there would be no difference in the resolution of triggering. METHODS: Our study was a prospective, single-blinded, randomized controlled trial at a single institution, comprising 76 patients with a diagnosis of trigger finger. Each treatment group consisted of 38 patients. Patients were randomized to receive either a betamethasone (1 mL, 6 mg) injection without lidocaine or a betamethasone injection (1 mL, 6 mg) with 1% lidocaine (1 mL). Patients were assessed during injection and at 1 hour, 6 hours, 2 days, and 6 weeks after the injection. The primary outcome was pain measured using a numerical rating scale. The secondary outcome was the rate of failure to resolve symptoms at 6 weeks. RESULTS: There was a statistically significant difference in pain scores between the lidocaine and betamethasone versus betamethasone-only injections during administration (4.6 vs 6.2) and after 1 hour (1.3 vs 2.5). There was no statistically significant difference in pain scores after 6 hours (1.5 vs 2.0) and 2 days (0.7 vs 0.6) or in failure rate at the 6-week time point (21% vs 18%). CONCLUSIONS: This study showed that there is a statistically significant difference in pain during and shortly after injection when using a steroid with lidocaine versus steroid alone for the treatment of trigger finger, but that difference may not be clinically relevant. There was no significant difference in the failure rate between the treatments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Mapping Origins of Tendons on the Medial Epicondyle to Improve Treatment of Medial Epicondylitis: Anatomical Study.

PURPOSE: Medial epicondylitis is a tendinosis found commonly in throwing and golfing athletes. Although there are choices for nonsurgical treatments, when these fail, surgical intervention can be considered. When surgical treatment is performed, the objective is to debride the diseased tissue from the epicondyle. The purpose of this study was to clarify the locations and size of the common flexor tendons and medial collateral ligament (MCL) relative to each other and to the posterior ridge of the medial epicondyle. METHODS: The common flexor tendons and MCL were dissected and reflected their origin on the medial epicondyle in six cadaver elbows. Measurements were taken from the posterior and distal ridges of the medial epicondyle with respect to the humerus. Each origin was also measured for its height and width. RESULTS: The flexor carpi ulnaris origin starts at a mean of 4.2 mm from the posterior ridge of the medial epicondyle and extends anteriorly an average of 4.8 mm. The flexor carpi radialis starts at a mean of 4.2 mm from the posterior ridge and extends anteriorly an average of 7.4 mm. The pronator teres begins at a mean of 4.6 mm from the posterior ridge and extends an average of 5.7 mm anteriorly. The MCL starts at an average of 10.4 mm from the posterior ridge and extends 5.2 mm anteriorly. CONCLUSIONS: The measurements found have allowed the creation of a map of the specific common flexor tendon origins and their sizes on the medial epicondyle, as well as their position relative to the MCL. CLINICAL RELEVANCE: A surgeon may debride 1 cm anteriorly from the posterior ridge of the medial epicondyle to safely address the affected tissues and ensure the safety and integrity of the MCL.

First total synthesis of asperilactone B. Revision of absolute stereochemistry of asperilactones B and C.

The first total synthesis and absolute configuration assignment of asperilactone B (I) have been accomplished. Additionally, a revision of the absolute stereochemistry of asperilactone C has been done. The first total synthesis of the opposite enantiomer of asperilactone B (ent-I) has also been achieved, as well as that of C-7 epimers of both asperilactones B (8) and C (9).

Synthesis and biological activity of thiophene bioisosteres of natural styryl lactone goniofufurone and related compounds.

Ten new thiophene derivatives related to goniofufurone have been obtained by multistep synthesis starting from d-glucose. The critical step of the synthesis was the Grignard reaction of 2-thienyl magnesium bromide with a protected dialdose, yielding the C-5 epimeric thiophene derivatives 9 and 10. The mixture was oxidized to the 5-keto derivative 11, which after deprotection was converted to the corresponding keto-lactone 14. Stereoselective reduction of 14 afforded the thiophene mimic of goniofufurone 3. Esterification of 3 with cinnamic or 4-fluorocinnamic acid gave hybrids 5-7. Synthesized analogues were evaluated for their in vitro cytotoxicity against several tumour cell lines. The vast majority of them showed better activity than lead 1. In the culture of K562 cells, compound 3 was more active than the commercial antitumour drug doxorubicin. Structural features of analogues important for their antiproliferative activities were identified by SAR analysis. Pro-apoptotic potential examination of compound 3 on the K562 cell line was performed using flow cytometry, double fluorescence staining and apoptotic morphology screening. Results show that this derivative induces cell membrane disruptions attributable to apoptosis and induces the apoptotic morphology, but decreasing simultaneously the population of cells in the subG1 phase of the cell cycle. The results further suggest that analogue 3 achieves strong cytotoxicity without causing DNA fragmentation. This is clearly indicated by the relatively low incidence of micronuclei, as well as the SAR analysis of all biological effects.

Cu(II) complexes with a salicylaldehyde derivative and α-diimines as co-ligands: synthesis, characterization, biological activity. Experimental and theoretical approach.

Copper(II) complexes with an α-diimine show a wide variety of biological activities, such as antibacterial, antifungal, antioxidant and anticancer. In this work, we synthesized and structurally characterized two novel Cu(II) complexes with methyl 3-formyl-4-hydroxybenzoate (HL) and α-diimines: 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen). Crystal structure analysis shows that the formulas of the compounds are [Cu(bipy)(L)(BF4)] (1) and [Cu(phen)(L)(H2O)](BF4)·H2O (2), with BF4- as a ligand in complex 1, which is rarely coordinated to metals. Both complexes have a square pyramidal geometry, while DFT calculations showed that the most stable structures of complexes 1 and 2 in a water/DMSO mixture are square-planar derivatives [Cu(bipy)(L)]+ and [Cu(phen)(L)]+. The antibacterial activity of compounds was evaluated in vitro on four Gram-negative and four Gram-positive bacterial strains. Complex 2 showed greater antibacterial activity towards all bacterial strains comparable to the control compound Amikacin. Complex 2 exerted a strong cytotoxic effect against the tested cancer cell lines (IC50 values ranging from 0.32 to 0.44 µM). Both complexes caused apoptotic cell death in HeLa cells and a noticeable in vitro antiangiogenic effect. In the concentration range of 5 to 100 µM, the complexes showed the absence of a genotoxic effect and displayed a protective effect against oxidative DNA damage induced by H2O2 in human peripheral blood cells. The interaction between the compounds and calf-thymus DNA was evaluated by diverse techniques suggesting a tight binding, which was also confirmed by molecular docking. In addition, it was found that the complexes bind tightly and reversibly to bovine and human serum albumin.

On the Selectivity in the Synthesis of 3-Fluoropiperidines Using BF3-Activated Hypervalent Iodine Reagents.

Fluorinated piperidines find wide applications, most notably in the development of novel therapies and agrochemicals. Cyclization of alkenyl N-tosylamides promoted by BF3-activated aryliodine(III) carboxylates is an attractive strategy to construct 3-fluoropiperidines, but it suffers from selectivity issues arising from competitive oxoaminations and the inability to easily modulate the reactions diastereoselectivity. Herein, we report an itemized optimization of the reaction conditions carried out on both cyclic and acyclic substrates and outline the origins of substrate- and reagent-based stereo-, regio-, and chemoselectivity. Extensive mechanistic studies encompassing multinuclear NMR spectroscopy, deuterium labeling, rearrangements on stereodefined substrates, and careful structural analyses (NMR and X-ray) of the reaction products are performed. This revealed the processes and interactions crucial for achieving controlled preparation of 3-fluoropiperidines using I(III) chemistry and has provided an advanced understanding of the reaction mechanism. In brief, we propose that BF3-coordinated I(III) reagents attack C═C to produce the corresponding iodiranium(III) ion, which then undergoes diastereodetermining 5-exo-cyclization. Transiently formed pyrrolidines with an exocyclic σ-alkyl-I(III) moiety can further undergo aziridinium ion formation or reductive ligand coupling processes, which dictate not only the final product's ring size but also the chemoselectivity. Importantly, the selectivity of the reaction depends on the nature of the ligand bound to I(III) and the presence of electrolytes such as TBABF4. Reported findings will facilitate the usage of ArI(III)-dicarboxylates in the reliable construction of fluorinated azaheterocycles.

Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations.

To improve the antiproliferative effect of ALC67 (diastereomeric mixture of ethyl 2-phenyl-3-propioloyl-1,3-thiazolidine-4-carboxylate), its structure was modified via (i) bioisosteric substitution of the phenyl ring by the ferrocene unit and (ii) replacing the propiolamide side-chain in ACL67 with other acyl groups having differing electrophilicities. In this way, a small library of methyl N-acyl-2-ferrocenyl-1,3-thiazolidine-4-carboxylates (13 compounds in total) was created and characterized by spectral and crystallographic means. The last N-acylation step was highly diastereoselective toward the cis-diastereomer. In solution, most of the obtained compounds existed as a mixture of two rotamers and displayed a preference for the syn-orientation around the CN bond. A twisted 5T4 envelope conformation was adopted by the derivative containing the N-phenoxyacetyl group in the crystalline state. Two derivatives with chloroacetyl and bromoacetyl groups in the N-3 side chain were cytotoxic to fibroblasts and hepatocellular cancer cells in the low micromolar range (IC50(MRC5) = 9.0 and 11.8 µM, respectively, and IC50(HepG2) = 10.6 and 18.4 µM, respectively) causing an effect similar to the lead compound (IC50(HepG2) = 10.0 µM) and cisplatin (IC50(MRC5) = 4.0 µM and IC50(HepG2) = 7.7 µM). Several derivatives also manifested modest antimicrobial effects against the studied microbial strains (MICs in the range from 0.44 to 4.0 µmol/mL). Our findings demonstrated that the introduction of a ferrocene core facilitated the preparation of optically pure analogs of ALC67 and that the cytotoxicity of compounds may be enhanced by adding proper electrophilic centers to the N-acyl side-chain.

Treatment of vascular non-iatrogenic injuries of upper and lower extremities in tertiary vascular center.

BACKGROUND: The purpose of this study was to examine demographic and baseline characteristics of patients with vascular injuries of extremities and to define the most relevant factors which influenced an early outcome, as well as limb salvage after the management of vascular trauma. METHODS: This study used the database that included 395 patients with peripheral arterial injuries, who were treated in the tertiary vascular university center in the period between 2005-2020. Exclusion criteria were isolated thoracic, abdominal and neck injuries as well as iatrogenic injuries and injuries of intravenous addicts. Univariate binary logistic regression analysis and multiple logistic regression were used to determine risk factors for lomb loss (after vascular reconstruction) or mortality. Decision to perform primary amputation (without vascular reconstruction) was based on surgeons' preference and experience. RESULTS: Out of 395 vascular injuries treated in the period 2005-2020, 210 (53.2%) presented with non-iatrogenic vascular injuries of upper and lower extremities were analyzed. According to the univariate regression analysis, hemorrhage as the main clinical manifestation on admission (P=0.035) and early reintervention (P=0.048) increased, while an early patency of repaired artery (0.010) significantly decreased a 30-day amputation rate. Multivariate logistic regression analysis of these three variables showed that only early patency of repaired artery significantly decreased the early amputation rate (P=0.009). CONCLUSIONS: Based on presented experience, the patency of vascular reconstruction plays a crucial role in limb salvage in patients with non-iatrogenic peripheral vascular injuries. All factors that might influence the patency should be in focus of improvement.

The first total synthesis and revision of absolute stereochemistry of natural cytotoxic lactone cleistanolate.

Development of a synthetic route applicable to d-ribose and d-xylose enabled the synthesis of cleistanolate putative structure, its five stereoisomers, and led to revision and confirmation of absolute stereochemistry of the natural product. Key steps of the synthesis included zinc-mediated THF ring-opening and stereoselective dihydroxylation under the Upjohn conditions. The first total synthesis of cleistanolate was completed in eight steps starting from d-xylose. The C-5 stereocenter of the natural product was assigned the correct (5S)-stereochemistry. Cytotoxicity of natural product was briefly investigated.

Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation.

Synthesis of protulactone A (PLA, 1) and twelve of its analogues have been achieved starting from d-galactose. PLA was isolated in the crystalline state, and its crystal structure was determined utilizing X-ray crystallography, which confirmed the assumed stereochemistry at all stereocenters. All tested compounds displayed antiproliferative activity against a panel of tumour cell lines, and all of them were non-cytotoxic toward the normal cells (MRC-5). Natural product PLA (1) was the most active against the K562 and MCF-7 cell lines (IC50 6.52 and 2.20 µM, respectively). Some of the synthesized derivatives showed very potent cytotoxicity, especially analogues 11, 13 and 15 (IC50 1.08-1.14 µM against MCF-7), and 9 and 14 (IC50 1.29 and 1.64 µM against K562). SAR analysis indicated important structural motifs for antiproliferative activity. Unfortunately, PLA (1), its C-7 epimer (2) and demethylated analogue (3) did not display a significant antimicrobial activity (two Gram-positive and two Gram-negative bacteria and one fungal strain) and they also cannot affect the ability to modulate bacterial communication.

Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity.

The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 µM.

Full-Self-Powered Humidity Sensor Based on Electrochemical Aluminum-Water Reaction.

A detailed examination of the principle of operation behind the functioning of the full-self-powered humidity sensor is presented. The sensor has been realized as a structure consisting of an interdigitated capacitor with aluminum thin-film digits. In this work, the details of its fabrication and activation are described in detail. The performed XRD, FTIR, SEM, AFM, and EIS analyses, as well as noise measurements, revealed that the dominant process of electricity generation is the electrochemical reaction between the sensor's aluminum electrodes and the water from humid air in the presence of oxygen, which was the main goal of this work. The response of the sensor to human breath is also presented as a demonstration of its possible practical application.

Is Colorectal Cancer Stage Affected by COVID-19 Pandemic?

Background: Causing healthcare systems overload, COVID-19 pandemic has a huge influence on patients with colorectal cancer. The aim of our study was to assess the potential impact of COVID-19 on the stage of colorectal cancer. Methods: In our retrospective study, two groups of patients operated for colorectal cancer were analyzed at the Clinic for Surgery "Nikola Spasic", Zvezdara University Medical Center. The study group consisted of 49 patients operated in the period from March 15, 2020 to April 2021, during COVID-19 pandemic. The control group consisted of 152 patients, who were operated on in the period from January 1, 2019. to December 31, 2019. Results: There were no difference in surgical approach, prevalence of stoma, percentages of postoperative complications and rates of hospital readmission between both groups. T4b tumor stage was statistically significant more common in the study group (12.2% vs 3.3%, p=0.027). Locally advanced tumors, stage IIC, were statistically significantly more common in the group of patients operated on during the COVID-19 pandemic (10.2% vs 1.3%, p=0.01). Conclusion: Higher number of locally advanced tumors in study group could probably be caused by the impact of the COVID-19 pandemic on healthcare system.

Ultrafast humidity sensor based on liquid phase exfoliated graphene.

Humidity sensing is important to a variety of technologies and industries, ranging from environmental and industrial monitoring to medical applications. Although humidity sensors abound, few available solutions are thin, transparent, compatible with large-area sensor production and flexible, and almost none are fast enough to perform human respiration monitoring through breath detection or real-time finger proximity monitoring via skin humidity sensing. This work describes chemiresistive graphene-based humidity sensors produced in few steps with facile liquid phase exfoliation followed by Langmuir-Blodgett assembly that enables active areas of practically any size. The graphene sensors provide a unique mix of performance parameters, exhibiting resistance changes up to 10% with varying humidity, linear performance over relative humidity (RH) levels between 8% and 95%, weak response to other constituents of air, flexibility, transparency of nearly 80%, and response times of 30 ms. The fast response to humidity is shown to be useful for respiration monitoring and real-time finger proximity detection, with potential applications in flexible touchless interactive panels.

Treatment of pediatric vascular injuries: the experience of a single non-pediatric referral center.

BACKGROUND: Pediatric peripheral vascular trauma carries significant risk of complications including limb loss and long-term invalidity. Mechanisms and types of morphological lesions are very diverse. The objectives of this study are to present the experience of a single vascular center in the surgical approach to pediatric vascular injuries, and to analyze the main challenges related to this clinical entity. METHODS: Over a period of 25 years, 17 pediatric peripheral vascular injuries were treated in our institution. Patient's age ranged between one day (newborn) and 15 years (mean: 10.7 years). There were five injuries of upper and 12 injuries of the lower extremity. Preoperative diagnosis was established by clinical examination (N.=4), ultrasonography (N.=1) and angiography (N.=12). Blunt trauma mainly caused arterial thrombosis while penetrating trauma caused arterial laceration or complete transection. Five patients had associated orthopedic injuries (29,4%). There were two posttraumatic pseudoaneurysms and two arterio-venous fistulas. RESULTS: There was no perioperative mortality. Vascular reconstructions included arterial suture (N.=4), thrombectomy + patch angioplasty (N.=1), termino-terminal anastomosis (N.=3), venous anatomic bypass (N.=6), PTFE graft reconstruction (N.=2), and venous extra-anatomic reconstruction (N.=1). Two patients had associated venous injury demanding both arterial and venous reconstruction. In the only case of war trauma treatment ended with limb loss. Other reconstructions presented good early and long-term patency. CONCLUSIONS: Pediatric vascular injuries are extremely challenging issues. Treatment includes broad spectrum of different types of vascular reconstructions. It should be performed by vascular surgeon trained in open vascular treatment or pediatric surgeon with significant experience in vascular surgery.

Reinforcement Learning-Based Adaptive Insulin Advisor for Individuals with Type 1 Diabetes Patients under Multiple Daily Injections Therapy.

The existing adaptive basal-bolus advisor (ABBA) was further developed to benefit patients under insulin therapy with multiple daily injections (MDI). Three different in silico experiments were conducted with the DMMS.R simulator to validate the approach of combined use of self-monitoring of blood glucose (SMBG) and insulin injection devices, e.g. insulin pen, as are used by the majority of type 1 diabetes patients under insulin therapy. The proposed approach outperforms the conventional method, as it increases the time spent within the target range and simultaneously reduces the risks of hyperglycaemic and hypoglycaemic events.

A novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cells.

A novel binuclear Cd complex (1) with hydrazone-based ligand was prepared and characterized by spectroscopy and single crystal X-ray diffraction techniques. Complex 1 reveals a strong pro-apoptotic activity in both human, mammary adenocarcinoma cells (MCF-7) and pancreatic AsPC-1 cancer stem cells (CSCs). While apoptosis undergoes mostly caspase-independent, 1 stimulates the activation of intrinsic pathway with noteworthy down regulation of caspase-8 activity in respect to non-treated controls. Distribution of cells over mitotic division indicates that 1 caused DNA damage in both cell lines, which is confirmed in DNA interaction studies. Compared to 1, cisplatin (CDDP) does not achieve cell death in 2D cultured AsPC-1 cells, while induces different pattern of cell cycle changes and caspase activation in 2D cultured MCF-7 cells, implying that these two compounds do not share similar mechanism of action. Additionally, 1 acts as a powerful inducer of mitochondrial superoxide production with dissipated trans-membrane potential in the majority of the treated cells already after 6 h of incubation. On 3D tumors, 1 displays a superior activity against CSC model, and at 100 µM induces disintegration of spheroids within 2 days of incubation. Fluorescence spectroscopy, along with molecular docking show that compound 1 binds to the minor groove of DNA. Compound 1 binds to the human serum albumin (HSA) showing that the HSA can effectively transport and store 1 in the human body. Thus, our current study strongly supports further investigations on antitumor activity of 1 as a drug candidate for the treatment of highly resistant pancreatic cancer.