Treatment Procedures Research Articles

Probing Dual Covalent Irreversible Inhibition of EGFR/FGFR4 by Electrophilic-Based Natural Compounds to Overcome Resistance and Enhance Combination Therapeutic Potentials and Management of Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is one of the most prevalent cancer types in the world and accounts for the majority of cases of primary liver cancer. A crucial part of the carcinogenesis of HCC involves aberrant stimulation of the FGF19-FGFR4 signaling pathway. Therefore, FGFR4 inhibition has become a strategic therapeutic approach for the treatment of HCC. However, the clinical treatment procedure is significantly hampered by the prevalence of kinase inhibitors resistance. It was recently established that the activation of EGFR signaling was found to be one of the primary mechanisms mediating the acquired resistance to FGFR4 inhibitors, moreover, sensitivity to FGFR4 inhibitors was effectively restored by inhibiting EGFR. These results provide compelling evidence that dual inhibition of EGFR and FGFR4 could represent a viable therapeutic approach to overcome resistance, hence enhanced management of HCC. To this end, we proposed a dual irreversible inhibition strategy through covalent binding by naturally occurring electrophilic warhead-bearing compounds (curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A and andrographolide) to covalently target both EGFR and FGFR4 through cysteine residues, Cys797 and Cys552, respectively. Covalent docking and covalent molecular dynamics (MM/MDcov) simulations combined with thermodynamic binding free energy calculations were performed, and the results were compared against known potent and selective covalent EGFR and FGFR4 inhibitors with available X-ray crystal structures, Afatinib and BLU9931, respectively. Curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A, and andrographolide showed relative binding free energies of -22.85, -17.14, -12.98, -21.81, and - 19.00kcal/mol against EGFR and - 41.06, -29.45, -24.76, -40.11, and - 37.55kcal/mol against FGFR4, respectively. The mechanisms of binding were emphasized by hydrogen bonding and binding forces analysis as well as active site physicochemical profiling. The findings of this study identified that curcumin, syringolin A and andrographolide-but not eupalmerin acetate or deoxyelephantopin -could be viable dual EGFR and FGFR4 covalent irreversible inhibitors and could be implemented in HCC combination therapy protocols alone or in conjunction with other chemotherapeutic agents. Investigations of this study conclusively indicate dual blockade of EGFR and FGFR4 may be a promising future therapeutic strategy for enhanced management of HCC.

Recurrent catamenial hemoptysis: diagnostic challenges and management strategies—a case report

Catamenial hemoptysis (CH) is a rare, known disease for which diagnosis is crucial and treatment is indefinite. In this case report, CH was identified 2 years ago while taking medical history of the patient. It has disclosed hemoptysis at night with breathlessness that was concurrent with her menses every month for the past 6 months. A series of radiological tests followed by a bronchoscopic examination during menses confirmed the diagnosis. A complex fluid-filled cystic lesion with few air foci in the right lower lobe superior segment with ground glass opacity was seen by a CT scan test. Subsequent bronchoscopy examination showed an active bleeding site at the right lower lobe superior segment. The bronchial wash tests were negative for microbial infections as well as for malignancies. Bronchial artery embolization (BAE) was done and it ceased the hemoptysis. However, it recurred after 2 years of the BAE procedure. The symptoms and amount of hemoptysis were milder; hence, repeated BAE was not required. Earlier, the patient refused hormonal therapy (HT) owing to its side effects, but this time, she accepted HT. After 2 months of HT, hemoptysis gradually ceased. If complications arise in the future, then surgical treatment along with HT (combination therapy) would be the course of treatment. The diagnosis of CH is challenging, and treatment procedures vary from patient to patient; hence, they are customised. Hormones regulate the CH recurrence even though the symptoms have ceased after treatment. Therefore, regular follow-up and close vigilance are crucial requirements.

Impact of veterinary pharmaceuticals on environment and their mitigation through microbial bioremediation

Veterinary medications are constantly being used for the diagnosis, treatment, and prevention of diseases in livestock. However, untreated veterinary drug active compounds are interminably discharged into numerous water bodies and terrestrial ecosystems, during production procedures, improper disposal of empty containers, unused medication or animal feed, and treatment procedures. This exhaustive review describes the different pathways through which veterinary medications enter the environment, discussing the role of agricultural practices and improper disposal methods. The detrimental effects of veterinary drug compounds on aquatic and terrestrial ecosystems are elaborated with examples of specific veterinary drugs and their known impacts. This review also aims to detail the mechanisms by which microbes degrade veterinary drug compounds as well as highlighting successful case studies and recent advancements in microbe-based bioremediation. It also elaborates on microbial electrochemical technologies as an eco-friendly solution for removing pharmaceutical pollutants from wastewater. Lastly, we have summarized potential innovations and challenges in implementing bioremediation on a large scale under the section prospects and advancements in this field.

Suction use in ureterorenoscopy: A systematic review and meta‐analysis of comparative studies

AbstractObjectivesUreterorenoscopy is seeing a bloom of technological advances, one of which is incorporating suction. The objective of this study is to systematically review existing literature regarding suction use in rigid and flexible ureterorenoscopy and perform meta‐analysis of studies comparing suction versus no suction ureteroscopy or mini percutaneous nephrolithotomy (PCNL).MethodsA literature search was performed (November 2023) in MEDLINE, Embase and Cochrane CENTRAL. Study protocol was registered at PROSPERO (CRD42023482360). Comparative studies (observational and randomized) were eligible for inclusion if they compared suction versus no suction group and reported at least one primary outcome of interest (stone‐free or complication rate).ResultsSixteen studies (5 randomized and 11 observational), analysing 1086 and 1109 patients in standard and suction groups, respectively, were included. Final stone‐free rates (SFRs), overall and infectious complications and length of hospital stay exhibited significant improvement when suction was used. When mini‐PCNL was compared with flexible ureterorenoscopy with suction, no differences were found in terms of stone‐free and infectious complications rates.ConclusionsUreterorenoscopy is a commonly performed endoscopic procedure for urolithiasis treatment, the success of which is defined by SFRs and complication rates. Application of suction via ureteral access sheaths, ureteral catheters or scopes may provide improved SFRs, reduced overall and infectious complication rates, along with a reduction in length of hospital stay. Further randomized studies are needed to validate these findings and standardize indications and protocols.

Perinatal management for fetal oral epignathus with duplication of the pituitary gland (DPG)-plus syndrome: A case report and literature review.

The prenatal diagnosis of epignathus presents a unique challenge for physicians. Differential diagnosis is usually based on the anatomic location of the tumor. Typical prenatal ultrasound characteristics of epignathus include a mixed solid and cystic lesion with vascularity in the solid component, originating from the hard or soft palate, and it is often associated with other anomalies such as craniofacial clefts or trans-sphenoidal intracranial extension. Herein, we present a case of prenatal diagnosis of epignathus with rare ultrasonographic findings, prenatal management requiring collaborative efforts of a multidisciplinary team, and a well-planned innovative ex utero intrapartum treatment procedure. In addition, this report highlights the evolving postnatal diagnosis of the rare developmental anomaly, duplication of the pituitary gland-plus syndrome, which includes various midline craniofacial, central nervous system, spinal, and endocrine abnormalities.

Apoptotic effects of biodentine, calcium-enriched mixture (CEM) cement, ferric sulfate, and mineral trioxide aggregate (MTA) on human mesenchymal stem cells isolated from the human pulp of exfoliated deciduous teeth.

Preservation of primary teeth in children is highly important. Pulpotomy is a commonly performed treatment procedure for primary teeth with extensive caries. Thus, biocompatibility of pulpotomy agents is highly important. Biodentine, calcium enriched mixture (CEM) cement, ferric sulfate, and mineral trioxide aggregate (MTA) Angelus are commonly used for this purpose. Thus, this study aimed to assess the apoptotic effects of Biodentine, CEM cement, ferric sulfate, and MTA on stem cells isolated from the human pulp of exfoliated deciduous teeth. In this in-vitro, experimental study, stem cells isolated from the human pulp of exfoliated deciduous teeth were exposed to three different concentrations of Biodentine, CEM cement, ferric sulfate, and MTA for different time periods. The cytotoxicity of the materials was evaluated by flow cytometry using the annexin propidium iodide (PI) kit. Data were analyzed by ANOVA and Tukey's test at P<0.05 level of significance. All four tested materials induced significantly greater apoptosis compared with the control group. The difference in cell apoptosis caused by the first concentration of ferric sulfate and MTA was not significant at 24 hours. In other comparisons, the cytotoxicity of ferric sulfate was significantly lower than that of other materials. Biodentine showed higher cytotoxicity than MTA at first; but this difference faded over time. The cytotoxicity of CEM cement was comparable to that of MTA. The highest cell viability was noted at 24 hours in presence of the minimum concentration of ferric sulfate. The lowest cell viability was noted at 72 hours in presence of the maximum concentration of CEM cement. In comparison with other materials, ferric sulfate showed minimum cytotoxicity; the cytotoxicity of the three cements was comparable. It appears that the concentration of ferric sulfate and the composition of cements are responsible for different levels of cytotoxicity.

Flexible Ureteroscopy versus Retroperitoneal Laparoscopic Ureterolithotomy in the Management of upper Ureteric Stones Measuring from One to Two Centimeters: Randomized Prospective Study

Abstract Objective This prospective study aims to compare the clinical efficacy and safety of flexible ureteroscopy versus laparoscopic ureterolithotomy in the management of upper ureteric stones measuring from one to two centimeters. Methods his randomized-prospective study was conducted on 64 patients admitted from Urology unit, Ain Shams University in the period from October 2020 till September 2022; only 56 patients were analyzed statistically and 8 patients were excluded due to shortage in post- operative data and follow up. Patients were divided into two groups Group A consists of 31 patients and Group B consists of 25 patients with matched age, gender and body mass index (BMI). Results In our study, The VAS score at 6 hours post-operative and day 1 post-operative was found to be 5.32 and 2.71 in FURS group and was found to be 7.28 and 3.28 in RPLU group respectively showing significant difference with (p- value &amp;lt;0.001 and 0.016 respectively) between the two groups with more satisfaction in FURS group mostly due to the absence of trocars incisions. The complications were classified according to modified Clavien classification system. No major complications such as septic shock or death were reported in either treatment groups. As regards the recovery to work in postoperative and follow up periods in the present study, there was a significant difference between both groups with (P-value &amp;lt;0.001), as we found that it takes about 4.56 ± 0.82 days in RPLU group and 3.06 ± 1.91 days in FURS group to return daily routine activities. As regards the stone free rate in follow up periods in the present study, there was a significant difference between both groups with (P-value 0,02), as we found that it was 100% and 80,6% in RPLU and FURS group respectively. Our success rate in RPLU group was found to be 100% in comparison to Irfan Nazir Mir et al which was 93.4% (28/30) with two patients (2/30) converted to open ureterolithotomy, either due to technical snag or due to difficulty in localizing the ureter laparoscopically. Conclusion Both F-URS and RTLU were safe and effective surgical procedures for treatment of large proximal ureteral stones. However, RTLU had a higher stone-free rate with comparable operating time and complication rate as compared to F-URS. Also as regards to postoperative pain, shorter hospital stay and faster return to daily activities, both have almost similar results.

Management of Common Bile Duct Stones: Evaluation of the Effect of Size of Stones as the Determinant for the Procedure for Treatment in Era of Laparoscopic and Endoscopic Surgery

Abstract Background Common bile duct stones (CBDS) are estimated to be present in 10–20% of individuals with symptomatic gallstones. A variety of imaging modalities can be employed to identify the condition while management of confirmed cases of CBDS may involve endoscopic retrograde cholangiopancreatography (ERCP), surgery and radiological methods of stone extraction. Clinicians are therefore confronted with a number of potentially valid options to treat individuals with suspected CBDS. Objective To determine if ERCP sphincterotomy and extraction is effective in management of CBDS ranging from 10 to 20 mm or if surgical intervention is preferred in a sample of patients with common bile duct stones. Patients and Methods In this study, the data of (30) patients with CBDS who presented for the first time to the department of General surgery at Ain Shams University hospitals, Cairo, Egypt. Were collected during the period of August 2021 to February 2022. Results In the current study, all patients received proper pre-operative assessment and were operated on using same endoscope set and by experienced operators. Also, all patients were observed for post ERCP complications. The current study found that ERCP stone extraction in stones ranging from 10-20 mm success rate shows no significant difference in comparison with results that were published in different recent researches studying ERCP success rate in different stone sizes. Conclusion The current study found that success rate of ERCP in CBD stones extraction in stones ranging from 10-20 mm in size is similar to success rate in stone extraction compared to other studies not specifying stone size range. Also, complication rate was comparable to other recent published studies’ complication rate.

Assessment of Anti-Reflux Suture in One Anastomosis Gastric Bypass for Prevention of Biliary Gastritis

Abstract Background Obesity continues to be a leading public health concern associated with many comorbidities and major hindering effect on the daily lifestyle of many people around the world. Surgical treatment for obesity has proved that it is the best and most effective, durable means of preventing the life-threatening complications and serious problems associated with morbid obesity. Objective Assessing the effect of the anti-reflux suture on the incidence and clinical consequences of bile reflux in OAGB Procedure. Patients and Methods In this prospective randomized study, 30 patients were selected in Ain Shams University hospitals between November 2021 and May 2022 for assessment of impact of Anti reflux suture on the incidence of post OAGB biliary gastritis. Results The cases presented in this study did not undergo upper GI endoscopy when they presented with symptoms of reflux or gastritis and thus it was not possible to differentiate between the presence of GERD or biliary gastritis as the source of their symptoms. Conclusion OAGB is safe and one of the leading procedures for treatment of obesity but it is still surrounded by controversy regarding its relation and effect on bile reflux gastritis. As far as this study shows, the anti-reflux suture modification alone does not seem to prevent the incidence of biliary reflux gastritis post OAGB.

Fascia Iliaca Block versus Femoral Nerve Block as Post Operative Analgesia in Total Hip Arthroplasty

Abstract Background Total hip arthroplasty (THA) are common surgical procedures for treatment of the degenerative disorders and traumatic diseases. However, a majority of patients often experience moderate to severe postoperative pain after THA. Postoperative pain control has a significant impact on earlier ambulation, initiation of physiotherapy, and better functional recovery. In addition, effective pain control would lower the length of hospital stay and the risk of thrombotic events which improves patients’ satisfaction. Objective To assess the efficacy and safety of FICB compared with FNB. Patients and Methods After approval of anesthesiology department scientific and ethical committees in Ain Shams University Hospitals, patients were included in the study, and were divided into two groups (n = 20; each); group FICB and FNB group. Group FICB: Patients (n = 20) of this group received ultrasound guided Fascia iliaca compartment block (FICB) before spinal anesthesia using 20-40 ml of 0.25% bupivacaine. Group FNB: Patients (n = 20) of this group received ultrasound guided femoral nerve block (FNB) before spinal anesthesia using 20-40 ml of 0.25% bupivacaine. Results The two groups were adequately monitored and assessed post-operatively and they were compared regarding analgesic outcome by using the visual analogue scaling system, besides, recording time for first call for rescue analgesia. Demographic data, post-operative hemodynamics, and sedation score were also assessed. Conclusion Fascia iliaca compartment block is effective for pain relief during the early post- operative period after total hip arthroplasty. Meanwhile, it can reduce the cumulative meperidine consumption and the risk of opioid-related adverse effects.

Pure red cell aplasia among ABO mismatched hematopoietic stem cell transplant recipients: a 13-years retrospective study and literature review

BackgroundPure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload.MethodsWe performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected.ResultsThe literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p&amp;lt;0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p&amp;lt;0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders.ConclusionsStandardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers.

Comparison between Palonosetron and Ondansetron in Prevention of Chemotherapy Induced Nausea Vomiting

Background: Chemotherapy induced nausea and vomiting (CINV) is the commonest and the most incapacitating experience of thepatient undergoing cancer chemotherapy. Poorly controlled CINV sometimes make patients to refuse further treatment. This study aimed to compare the efficacy and safety of Palonosetron and Ondansetron in preventing CINV during cancer chemotherapy. Methods:This randomized controlled trial was conducted in the Department of Pharmacology and Therapeutics of Sylhet MAG Osmani Medical College from January 2021 to December 2021. There were 190patients enrolled initially; 14 patients from both groups withdraw themselves. Finally, 91 patients of Palonosetron and 85 patients of Ondansetron treated were recruited. The Palonosetron group were treated with Palonosetron at 0.25 mg and the Ondansetron group were treated with Ondansetron 8.0 mg intravenously, 30min before chemotherapy. After that Palonosetron 0.5 mg single time and Ondansetron 8.0 mg orally three times a day were given and total follow-up period was seven days. Episode of nausea and vomiting graded according to the guideline “Common Terminology Criteria for Adverse Events (CTCAE)”, version 4.0, which was published by the US Department of Health and Human Services (National Institute of Health and National Cancer Institute). Result: The groups were matched for the age (p = 0.263), gender (p = 0.630), body weight (p = 0.846),site of malignancy (p = 0.375), and drugsused for chemotherapeutic (p = 0.301) in both study groups. Palonosetron treated patients experienced significant lower episode of nausea in day-1 (p = &lt;0.001) and day-2 (p = 0.025), and in case vomiting in day-1 (p = 0.026) compared to Ondansetron. Significantly higher number of patients of Palonosetron compared to Ondansetron treated group showed complete response in both acute phase (p = 0.026), delayed phase (p = 0.036) and finally in overall phase (p = 0.014). Only four patients experienced with treatment failure in Ondansetron treated group. Observed adverse effects were in low intensity and not caused to stop the treatment procedure. Conclusion: Palonosetron was found to be more efficacious and well tolerated in preventing acute, delayed and overall phase of chemotherapy induced nausea and vomiting in this study.

Role of percutane peritoneal drainage in management of neonatal pneumoperitoneum: is surgery always necessary?

Aims: The standard procedure in the management of neonatal pneumoperitoneum (NP) cases is laparotomy. However, in some of the cases in which surgery is not a viable option, percutaneous peritoneal drainage (PD) can be performed in order to stabilize the patient prior laparotomy. This study reviews the role of PD in NP patients using previous studies in the literature. Methods: 26 neonates diagnosed with NP in Van Yüzüncü Yıl Faculty of Medicine, Van Training and Research Hospital neonatal ICU from April 2015 to January 2018 were retrospectively reviewed. In terms of surgical assessment, patients were divided into 2 groups according to their birth weight. Group A consisted of neonates with birth weight above 1000 grams whereas Group B consisted of neonates with birth weight above 1000 grams whereas Group B consisted of neonates with a birth weight of 1000 grams or below. Demographic values, diagnosis, and treatment methods were put on record in patient files. Results: 10 cases (7 male – 3 female) in Group A had a mean body weight of 1850 (Range: 1070 – 3400 gr) grams. In this patient group, NP developed as a result of pneumothorax, necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP). 3 (30%) of the patients who were treated with classical approaches were lost during the treatment period. Group B consisted of 16 (9 male – 7 female) patients with a mean body weight of 780 (Range 470 – 950) grams. In this case group, NP developed as a result of NEC. PD was performed prior to conventional treatment procedures and 5 (31%) of the patients were lost during the treatment period. Conclusion: Group B had similar mortality rates with Group A. result explains to us that PD is a viable option in stabilizing the patient prior to laparotomy as a starting procedure, especially in neonates below 1000 grams and deemed as surgically unstable.

Exploiting multivariate network meta-analysis: A calibrated Bayesian composite likelihood inference.

Multivariate network meta-analysis has emerged as a powerful tool in evidence synthesis by incorporating multiple outcomes and treatments. Despite its advantages, this method comes with methodological challenges, such as the issue of unreported within-study correlations among treatments and outcomes, which potentially lead to misleading conclusions. In this paper, we proposed a calibrated Bayesian composite likelihood approach to overcome this limitation. The proposed method eliminated the need to specify a full likelihood function while allowing for the unavailability of within-study correlations among treatments and outcomes. Additionally, we developed a hybrid Gibbs sampler algorithm along with the Open-Faced Sandwich post-sampling adjustment to enable robust posterior inference. Through comprehensive simulation studies, we demonstrated that the proposed approach yielded unbiased estimates while maintaining coverage probabilities close to the nominal level. Furthermore, we implemented the proposed method on two real-world network meta-analysis datasets; one comparing treatment procedures for the root coverage and another comparing treatments for anaemia in chronic kidney disease patients.

Evaluation of a Novel Ablative 1940 nm Pulsed Laser for Skin Rejuvenation.

Skin rejuvenation is a widely sought-after goal, prompting advancements in laser technology for noninvasive and effective treatments. Ablative lasers, in particular, have evolved to address diverse skin concerns, with fractional ablative lasers offering better-tolerated outcomes. The introduction of a novel ablative Thulium pulsed laser, based on Thulium-doped Yttrium aluminum Perovskite (Tm:YAP) crystal, delivers precise and controlled skin rejuvenation by allowing customization of ablative microcolumns. A pilot in vivo study was conducted on the abdominal skin of a live female pig. Using the Laser Team Medical (LTM) prototype laser, treatments were administered with varying coagulation settings (minimal and maximum) and energies (32, 80, 120, and 160 mJ per microcolumn). Biopsies were harvested, fixed, and stained for subsequent analysis. The penetration depth and width of the microcolumns were evaluated. Low coagulation settings produced ablative microcolumns with thermal affected zones of 160 µm width, while high coagulation settings resulted in wider zones of 400-530 µm. The ablation cavities' width was estimated to be less than 100 µm in both settings. The novel 1940 nm pulsed laser demonstrated superior microcolumn properties, offering potential advantages such as shorter downtime and increased efficacy compared to existing fractional ablative lasers. This study presents encouraging preliminary results regarding the efficacy and safety of the first ablative 1940 nm pulsed laser. The results show ablative microcolumns thinner than the counterpart devices, showing the device safety and potential higher efficacy along with short downtime. The LTM novel ablative 1940 nm pulsed laser holds immense potential for enhancing skin rejuvenation treatments due to its superior microcolumns properties. The versatility of this laser can open new treatment procedures and may extend to different areas of dermatology.

Assessment of the eutrophication status at Mediterranean sub-basin scale, within the European Marine Strategy Framework Directive

The aim of this work is to define harmonized reference conditions and assessment thresholds for selected criteria elements of the Marine Strategy Framework Directive (MSFD) Descriptor 5 (Eutrophication) in the Eastern Mediterranean Sea and to test if a tool for integrated assessment of the status of marine systems can be used as a common methodological approach. In this frame, we tested two statistical approaches in order to set threshold values for four criteria of Descriptor 5: nutrients, chlorophyll a, transparency and dissolved oxygen in the bottom waters. It is noteworthy that this work revealed the need to apply common procedures in data treatment and assessment evaluation. This is the first attempt to set common methods for the assessment of eutrophication in the Eastern Mediterranean, which is essential in marine environments, especially those shared by several countries. To this end, we have applied common criteria and metrics and established thresholds “Good” and “Moderate” for nutrients, chlorophyll a, transparency and dissolved oxygen in the bottom waters for the different Water Types of the Adriatic and Aegean Seas (I, II, IIIW, IIIE), based on datasets provided by Italy, Slovenia, Croatia and Greece. The selected criteria elements were common for all countries, providing a unified approach to GES assessment of two case study areas: the Adriatic Sea and the Saronikos Gulf. Dissolved Inorganic Nitrogen (DIN) threshold values of 15.6, 6.85, 1.61 and 2.11 μmol L−1 were set for the Water Types I, II, IIIW and IIIE, respectively.We also tested if an aggregation tool for GES assessment, such as Nested Environmental status Assessment Tool (NEAT), could be used as a common methodological approach. The comparison of NEAT with TRIX showed good comparability. In this end, NEAT can be used as a useful and much needed assessment tool for assessing eutrophication status of the marine.

An automation of Monte Carlo workflow for dosimetry study of an Elekta LINAC delivery system in radiotherapy

PurposeThis study aims to automate the Monte Carlo (MC) workflow utilized for radiotherapy dosimetry, focusing on an Elekta LINAC delivery system. It addresses the challenge of integrating MC simulations into routine clinical practice, making this accurate yet complex method more accessible and efficient for radiotherapy dosimetry. Methods and MaterialsWe developed a user-friendly software featuring a graphical user interface (GUI) that integrates EGSnrc for MC simulations. The software streamlines the process from retrieving Digital Imaging and Communications in Medicine (DICOM) data to executing dose calculations and comparing dose distributions. To validate our proposed tool, we compared its computed doses for IMRT and VMAT plans from the Pinnacle TPS for an Elekta Versa HD linear accelerator against MC simulation results. This comparison utilized our in-house software and GUI as the tool, covering various treatment sites and prescriptions. ResultsThe automated MC workflow demonstrated high accuracy in dose calculations and streamlined integration with clinical workflows. The comparison between the MC-simulated and TPS-calculated doses revealed excellent agreement, highlighting the reliability of MC for independent dose verification in complex treatment scenarios. ConclusionsThe automated MC workflow developed represents a substantial improvement in the practicality and efficiency of MC simulations in radiotherapy. This advancement not only simplifies the dosimetry process but also ensures high accuracy, establishing it as a valuable tool for routine patient-specific quality assurance and the development of specialized treatment procedures.

Clinical efficacy of a two-piece abutment conforming to the concept of one abutment one time in the posterior region: A clinical pilot study.

To assess the impact of a two-piece abutment workflow on enhancing the stability of the alveolar bone and gingiva surrounding the dental implant, and to determine the level of patient satisfaction. A total of 48 patients with dentition defect in the posterior region were included and divided into two groups: the two-piece abutment workflow (TAW) and the sealing screw with submerged healing workflow (SHW). Marginal bone level (MBL), soft tissue indicators, oral hygiene indicators, and patient satisfaction were assessed and recorded partially at 0, 3, 6, and 12 months after surgery. The primary outcome was the change of MBL in different time periods. A generalized linear mixed model (GLMM) was used to take into account the correlated nature of the data, and adjust for potential confounding factors within inter-group differences. The survival rate of implants and prosthesis reached 100% at 12-month follow-up, with an average decrease of 0.25 mm (SD 0.23 mm) of MBL in the TAW group and 0.48 mm (SD 0.45 mm) in the SHW group. The change of MBL in the TAW group (0.15 ± 0.31 mm) was significantly lower than the SHW group (0.41 ± 0.41 mm) through the analysis of GLMM within 6 months, while no significance was found in 12 months. Moreover, less gingival pain and oppression during prosthesis loading, and less time consumption overall duration were showed in the TAW group through Visual Analogue Scale (VAS, p < 0.05). Within a 6-month period, the two-piece abutment workflow showed superior efficacy in preserving the integrity of the marginal bone level. Furthermore, it streamlined treatment procedures and mitigated discomfort, hence increasing patient satisfaction.

Effect of heat treatment on the anisotropic mechanical properties and corrosion resistance of laser powder bed fusion fabricated Inconel 625

The microstructure evolution of laser powder bed fusion processed Inconel 625 after heat treatment at 650 ℃ (aging), 850 ℃ (sensitization) and 1050 ℃ (homogenization) was studied. Relationship of microstructure evolution and the anisotropic mechanical properties and corrosion resistance was analyzed. Decreased corrosion resistance after aging and sensitization was observed, which is related to the different precipitation behavior. After aging, γ″ and MC carbides precipitated along cellular structures further accelerate the corrosion along melting pool boundaries. While after sensitization, δ precipitated along cellular structures aggravated the corrosion along the melting pool boundaries. At the meantime, precipitation of M23C6 carbides and δ along grain boundaries made it vulnerable to be corroded, which further accelerate the corrosion rate. After homogenization, segregation and precipitates are barely observed in the microstructure which contribute to an enhancement of corrosion resistance. Moreover, with the increasing of heat treatment temperature, recovery of anisotropic microstructure contributes to the decrease of the anisotropy of mechanical properties. This study may contribute to the profound comprehension of heat treatment procedure on microstructure evolution as well as mechanical properties and corrosion resistance of laser powder bed fusion processed Inconel 625.

An analysis of PIK3CA hotspot mutations and response to neoadjuvant therapy in breast cancer patients from four prospective clinical trials.

The PI3K signaling pathway is frequently dysregulated in breast cancer (BC), and mutations in PIK3CA, are relevant for therapy resistance in HER2pos BC. Mutations in exons 9 or exon 20 may have different impact on response to neoadjuvant chemotherapy-based treatment regimens. We investigated PIK3CA mutations in 1691 early BC patients, randomized in four neoadjuvant multicenter trials: GeparQuattro (NCT00288002), GeparQuinto (NCT00567554), GeparSixto (NCT01426880) and GeparSepto (NCT01583426). The role of different PIK3CA exons and hotspots for pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) and patient survival was evaluated for distinct molecular subgroups and anti-HER2 treatment procedures. A total of 302 patients (17.9%) of the full cohort of 1691 patients had a tumor with a PIK3CA mutation, with a different prevalence in molecular subgroups: luminal/HER2neg 95 of 404 patients (23.5%), HER2pos 170 of 819 patients (20.8%) and TNBC 37 of 431 patients (7.9%). We identified mutations in PIK3CA exon 20 to be linked with worse response to anti-HER2 treatment (OR=0.507, 95%CI 0.320-0.802, p=0.004), especially in HR positive HER2 positive BC (OR=0.445, 95%CI 0.237-0.837, p=0.012). In contrast, exon 9 hotspot mutations p.E452K and p.E545K revealed no noteworthy differences in response therapy response. Luminal/HER2neg patients show a trend to have worse treatment response when PIK3CA was mutated. Interestingly, patients with residual disease after neoadjuvant treatment, have better survival when PIK3CA was mutated. PIK3CA hotspot mutation p.H1047R are associated with worse pCR rates after NACT in HER2pos BC, while hotspot mutations in exon 9 seems to have less impact.