Tailoring neoadjuvant systemic therapy in breast cancer: "The advent of a personalized approach"-The Breast-Gynecological and Immuno-Oncology International Cancer Conference (BGICC) consensus and recommendations.

BACKGROUND: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus. METHODS: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer. RESULTS AND CONCLUSIONS: The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified.

The Outcome of the WALANT Technique in Primary Hand Flexor Tendons Repair.

Introduction: Wide-awake local anesthesia and no tourniquet (WALANT) represents a revolutionary technique for hand surgeons who dismiss tourniquets and sedation. In this study, we present our experience with the WALANT technique in primary flexor tendon injuries of the hand. Patient and methods: This prospective research was carried out on 30 patients undergoing hand primary, flexor tendon repair surgery. Flexor tendon injury zones 2, 3, 4, and 5 were included. WALANT was prepared and injected. The tendons were surgically managed by a cruciate single cross-stitched locked 4-strand technique. The pain was assessed using a visual analog scale (VAS) score. The range of motion (ROM) of affected fingers was assessed according to the Strickland evaluation system. Results: There was a highly significant relationship between the patient's compliance with physiotherapy and obtained ROM of the affected finger with a P value <0.001. During injection of WALANT solution, 4 cases (13.3%) had no pain, 25 cases (83.3%) had mild pain (score 1-4), and 1 case (3.3%) had moderate pain (score 5-7). Conclusion: WALANT provides an optimal bloodless and comfortable field with an opportunity to assess the strength of tendon repair, gapping or triggering and managing them intra-operatively.

Cytogenetic Subclone Burden: A New Biomarker Predicting Chronic Lymphocytic Leukemia Patients Outcome.

BACKGROUND: Chronic lymphocytic leukemia is the most prevalent adult leukemia that occurs in older patients and presents a variable course of the disease. Risk stratification of CLL is a matter of continuous improvement. Thus, this study aimed to assess the impact of the quantification of 17p del and 11q del cytogenetic subclones on the outcome of patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: This is a prospective study that involved 100 subjects with CLL. For all included patients; assessment of the cytogenetic subclones burden for 17p del and 11q del using the FISH technique was carried out. RESULTS: CLL patients with a high 17p del (>33%) cytogenetic subclone burden showed significantly shorter lymphocyte doubling time (LDT), time to first treatment (TTFT), and progression free survival (PFS) compared to those with a lower burden. On contrary 11q del subclone(>30%) burden had an insignificant impact on LDT, TTFT and PFS. CONCLUSION: Quantification of 17pdel burden (>vs.≤33%) could be used for refining risk stratification of CLL patients.

Cross-leg flaps: Case series, review, and proposed classification.

Background: Cross-leg (CL) flap procedures have a long history in reconstructive surgery, having been described for the first time in 1854. The application of these flaps can potentially solve many reconstructive issues with satisfactory outcomes. Patients and methods: During our research into the history and development of CL flaps, we identified a variety of flaps for which a classification system can be proposed based on blood supply and flap modifications. In this study, 10 patients with different complaints were managed using posterior tibial artery (PTA) perforator CL flap and superiorly based sural CL flap with satisfactory outcomes. Results: All flaps survived and healed smoothly; consequently, the flaps provided stable coverage, and the donor sites were reconstructed using skin grafts, which provided satisfactory results to the patients and/or their guardians. Conclusion: To our knowledge, this is the first study to propose a simple classification and group different types of flaps mentioned in the literature under one category. CL flaps are a common reconstructive option for patients with injuries that limit their mobility.

Araucaria heterophylla oleogum resin essential oil is a novel aldose reductase and butyryl choline esterase enzymes inhibitor: in vitro and in silico evidence.

The essential oil isolated by hydrodistillation of the oleogum resin of Araucaria heterophylla has been analyzed by GC-MS. Twenty-four components accounting to 99.89% of the total detected constituents of this essential oil were identified. The major ones were: caryophyllene oxide (14.8%), ( +)-sabinene (12.07%), D-limonene (11.22%), caryophyllene (10.36%), α-copaene (8.00%), ß-pinene (6.44%), trans-verbenol (5.88%) and α-pinene oxide (5.18%). The in vitro inhibitory activities of this oil against aldose reductase, BuCHE, COX-2 and SARS-CoV-2 Mpro enzymes were evaluated. This revealed promising inhibitory activity of the essential oil against both aldose reductase and BuCHE enzymes. The molecular docking study of the major components of the Araucaria heterophylla essential oil was carried out to correlate their binding modes and affinities for aldose reductase and BuCHE enzymes with the in vitro results. In conclusion, the in vitro inhibitory activity of the essential oil attributed to the synergistic effect between its components and the in silico study suggested that compounds containing epoxide and hydroxyl groups may be responsible for this activity. This study is preliminary screening for the oil to be used as antidiabetic cataract and Alzheimer's disease therapeutics and further investigations may be required.

Design and Synthesis of New 4-(3,4,5-Trimethoxyphenyl)Thiazole-Pyrimidine Derivatives as Potential Antiproliferative Agents.

A new series of 3,4,5-trimethoxyphenyl thiazole pyrimidines has been synthesized and biologically evaluated for its in vitro anticancer activity. Compounds 4a, 4b, and 4h with substituted piperazine showed the best antiproliferative activity. In the NCI-60 cell line screening, compound 4b showed promising cytostatic activity against multiple cell lines. Notably, it elicited a GI value of 86.28% against the NSCL cancer cell line HOP-92 at a 10 µM dose. Compounds 4a and 4h at 10 µM showed promising GI values of 40.87% and 46.14% against HCT-116 colorectal carcinoma and SK-BR-3 breast cancer cell lines, respectively. ADME-Tox prediction of compounds 4a, 4b, and 4h revealed their acceptable drug-likeness properties. In addition, compounds 4a, 4b, and 4h showed a high probability of targeting kinase receptors via Molinspiration and Swiss TargetPrediction.

Prognostic value of MTSS1 gene expression on acute leukemia patients outcome.

Background: This study aimed to evaluate the prognostic value of the MTSS1 gene expression in patients with acute leukemia. Patients & methods: MTSS1 gene expression was quantified in 120 newly diagnosed acute leukemia patients, by quantitative reverse transcription PCR at diagnosis and after induction chemotherapy therapy. Results: Baseline MTSS1 gene expression was significantly higher in acute leukemia patients compared to the control group (p < 0.001). Acute leukemia patients with low baseline MTSS1 gene expression at diagnosis have significantly shorter overall survival and disease-free survival compared with those with higher expression (p < 0.001 for both). Conclusion: Downregulation of MTSS1 gene expression at diagnosis was associated with poor outcome in either cytogenetic acute myeloid leukemia or B-cell acute lymphoblastic leukemia.

New thiazole-based derivatives as EGFR/HER2 and DHFR inhibitors: Synthesis, molecular modeling simulations and anticancer activity.

New series of thiazole and imidazo[2,1-b]thiazole derivatives were synthesized and tested for their in vitro anticancer activity. Compounds 27, 34, 39 and 42-44 showed the best anticancer activity against the tested cancer cell lines with high safety profile and selectivity indices, especially MCF-7 breast cancer, compared to sorafenib. As an attempt to reveal their mode of cytotoxicity, EGFR, HER2 kinase and DHFR inhibition assays were performed. Compounds 39 and 43 were the most potent dual EGFR/HER2 kinase inhibitors, with IC50 values of 0.153 (EGFR), 0.108 (HER2) and 0.122 (EGFR), 0.078 (HER2) µM, respectively. 39 and 42 were the best DHFR inhibitors showing IC50 0.291 and 0.123 µM, respectively. 39 and 43 induced their cytotoxicity via cell cycle arrest at G1/S and G1 phases, respectively, and apoptosis rather than necrosis in the MCF-7 breast cancer cell line. In vivo anti-breast cancer assay of 39 and 43 showed significant tumor volume reduction with recovered caspase-3 immunoexpression. Modeling study results proved the importance of the 5-(4-substituted phenyl)-imidazo[2,1-b]thiazole moiety and the hydrazide side chain for the anticancer activity. The most potent compounds showed good drug-likeness features and could be used as prototypes for further optimization. 39 could be an example of a multi-targeting anticancer agent that acts by inhibiting EGFR/HER2 kinase, DHFR enzymes and cellular apoptosis.

Effect of Organic Selenium-Enriched Yeast on Relieving the Deterioration of Layer Performance, Immune Function, and Physiological Indicators Induced by Heat Stress.

Heat stress (HS) induces deleterious effects on the performance of laying hens and causes economic losses for poultry industry. This study was carried out to investigate the organic effect of selenium-enriched yeast (SY) on relieving the performance, immunity and physiological deterioration induced by heat stress in laying hens. A total of 324, 28-week-old, Hy-Line Brown commercial chicken layers were randomly distributed into 4 treatments according to a 2 × 2 factorial design, with 9 hens × 9 replicates per treatment (n = 81). From 30 to 34 weeks of age, layers were exposed to 2 temperature treatments (the HS treatment groups): a thermoneutral temperature at 24°C and a heat stress at 35°C. Layers were further assigned into the 2 subgroups according to dietary supplementation with organic selenium-enriched yeast (the SY treatment groups) at either 0 or 0.4 mg/kg diet. Results indicated that all the aspects of the layer performance during the experimental period were impaired by exposure to HS, while SY supplementation improved the layer performance in both the HS and non-HS layers. Intestinal villi disruptions and liver necrotic hepatocytes were observed in the layers exposed to HS, while villi integrity and hepatocytic normality were enhanced by SY treatment. A significant (P < 0.05) decrease in the total leukocyte count, sheep red blood cell (SRBC) antibody titer, and T- and B-lymphocyte proliferation along with an increase in the heterophils/lymphocytes (H/L) ratio were observed in the HS layers compared to non-HS layers. On the contrary, SY treatment significantly (P < 0.05) improved the immune function traits in both the HS layers and non-HS layers. Furthermore, the SY treatment plays an important role in mitigating the oxidative stress and inflammation induced by HS, displaying lower levels of plasma corticosterone, lipid peroxidation, interleukin-1ß, and tumor necrosis factor-α in HS layers supplemented with SY compared to HS layers without SY supplementation. These results conclude that addition of SY to the diet of laying hens could be applied as a potential nutritional approach to relieve the deterioration effects of heat stress on the immunity, physiological status, and productive performance of laying hens.

Facial Anthropometry and Analysis in Egyptian Women.

Human facial analysis can be considered both an art and a science, and is used extensively to measure soft tissue proportions. Remarkable changes exist in anthropometric measures due to changes over centuries of geographical, genetic, and environmental factors, as well as waves of migration causing facial proportions to vary among the different ethnic groups. The purpose of this study was to establish facial soft tissue norms for the Egyptian female population between the ages of 18 and 50, as well as several age-related changes in facial measurements that are described fairly scarcely in the literature. Methods: A prospective study was carried out on 300 Egyptian women between June 2019 and December 2020. All were volunteers and between 18 and 50 years old. Facial measurements were obtained by both direct (caliper-based) and indirect (3D Crisalix software) anthropometric analysis. Anthropometric measurements used in the study included seventeen facial measurements derived from different anthropometric soft tissue landmarks from each subject and eight measurements for analysis. Results: Our results were able to describe the average facial and nasal measurements of the Egyptian female population, as well as the horizontal and vertical analysis of facial proportions. We also determined similarities with other Middle Eastern female measurements, with subtle differences in facial width and nasal height and width compared with Turkish and Iranian women. Conclusions: The current study is valuable because it delivers facial anthropometric measures for Egyptian female faces. This can provide a database for a multitude of uses, including operative planning, postoperative measurements, and forensic and ergonomic purposes.

Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats

Abstract Cardiorenal syndrome is a life-threatening condition. The aim of the current study was to determine the cardioprotective effects of amlexanox in 5/6 nephrectomized rats. Rats were randomly assigned to three groups: sham, 5/6 nephrectomized rats, and amlexanox-treated 5/6 nephrectomized group. Amlexanox (25 mg/kg/day, i.p.) administration was started just after surgery and continued for 10 weeks. After treatment, kidney function (serum creatinine and urea) and blood pressure (systolic and diastolic) were measured. Heart weight (normalized to tibial length) and fibrosis area percentage were measured. Serum brain natriuretic peptide (BNP, heart failure marker) and cardiac levels of ß1-adrenergic receptor (ß1AR), ß-arrestin-2, phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol (DAG), pS473 Akt (a survival marker), and caspase-3 activity (an apoptosis marker) were also measured. The 5/6 nephrectomy caused renal impairment, cardiac fibrosis, apoptosis, and heart failure indicated by down- regulation of cardiac ß1AR down-stream signals compared with those in the sham group. Interestingly, amlexanox significantly reduced all cardiopathological changes induced after 10 weeks of 5/6 nephrectomy. Amlexanox showed potent cardiac antifibrotic and antiapoptotic effects in 5/6 nephrectomized rats, which were associated with reduced heart failure. To our knowledge, this is the first study that addresses the potent in vivo cardioprotective effects of amlexanox

The use of vitamin E in preventing taxane-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy. Several trials have evaluated the protective effect of vitamin E in preventing CIPN with controversial results. This study aims to outline the role of vitamin E in preventing CIPN. METHODS: A prospective phase II, open-label randomized controlled study was conducted in patients receiving taxane-based chemotherapy in Ain Shams University Hospitals, using vitamin E at a dose of 400 mg twice daily. The primary endpoint was the incidence of grade ≥ 2 sensory neuropathy according to CTCAE v 5.0 in each treatment arm. Secondary endpoints include time to onset and the duration of grade ≥ 2 sensory neuropathy. RESULTS: A total of 140 patients were randomized between the control and vitamin E arms. There was no difference in the incidence of grade ≥ 2 sensory neuropathy between the two arms (25.7% in each arm; P = 1.0), as well as the time to onset of neuropathy (P = 0.24). However, there was a statistically significant difference between the 2 arms as regards the duration of neuropathy. The median duration was 12.5 vs. 5 weeks in the control and vitamin E arms respectively (P = 0.01). CONCLUSION: Our study did not demonstrate a protective role of vitamin E in decreasing the incidence of CIPN in patients receiving taxane-based chemotherapy. However, the recovery from CIPN was much better as compared to the control arm, which may indicate a role for vitamin E in decreasing the duration and severity of CIPN.

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer.

Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

Evaluation of Cortactin and HS1 Genes Expression: New Players in Adult B-Cell Acute Lymphoblastic leukemia.

OBJECTIVES: This study aimed to assess the prognostic value of cortactin and HS1 genes expression in adult B-cell acute lymphoblastic leukemia. METHODS: The study included a cohort of 74 adult B-ALL patients and 76 controls. Cortactin and HS1 genes expression were quantified by real time PCR. RESULTS: The expression of cortactin and HS1 were significantly higher in B-ALL patients at diagnosis as compared to post induction levels (p.

2-Substituted-mercapto-quinazolin-4(3H)-ones as DHFR Inhibitors.

Antifolates are a class of drugs used as antibacterial, antiparasitic, and anticancer agents. This review focuses on 2-substituted-mercapto-quinazolin-4(3H)-one analogues as dihydrofolatereductase (DHFR) inhibitors. Several research work have concluded a structural model for this class of 2-thio-quinazoline derivatives to get compounds with remarkable biological activity. The pattern and orientation of the p-system substitutions with regard to the quinazoline nucleus manipulate the activity. The application of the obtained model criteria produced compounds 18, 20 and 21, which proved to be 4-8 times more active than the reference drug methotrexate (MTX, 1).

The first BGICC consensus and recommendations for breast cancer awareness, early detection and risk reduction in low- and middle-income countries and the MENA region.

In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.

Effect of fluoxetine on the testes of adult albino rats and the possible protective role of curcumin.

Fluoxetine (FLX) is extensively used for the treatment of a diversity of psychiatric disorders, mainly depression. However, it can adversely affect male fertility. This study was done to clarify the changes which take place in the testes after the oral administration of FLX and to evaluate the possible preventative role of curcumin. Seventy-six adult male albino rats were randomly divided into four equal groups. Control group: kept without any treatment. Curcumin group: received daily dose of curcumin (150 mg/kg body weight) through oral gavage for 8 weeks. FLX group. They were given daily dose of FLX (10 mg/kg body weight) given through oral gavage for 8 weeks. FLX and curcumin group. They were given FLX together with curcumin with the same previous doses through oral gavage daily for 8 weeks. By the end of the experiment, blood samples were collected for the biochemical study of testosterone. All the animals were anaesthetized by ether inhalation, and the testis specimens were dissected out and weighed. The specimens were subjected to histopathological, immunohistochemical, and morphometrical evaluation. FLX decreased serum testosterone, diminished both epithelial height and diameter of seminiferous tubules, increased collagen fiber deposition in testicular tissue and induced positive immune reaction to B-cell lymphoma-2-associated X protein. In the FLX and curcumin group, the FLX-induced changes were less remarkable. Exposure to FLX led to pronounced testicular alterations. Co-administration of curcumin with FLX ameliorated these changes.

Brain and Cardiac Concomitant Localization of the Hydatid Cyst.

Hydatid cyst is a parasitic infestation that is usually observed in the liver and lungs. The localization in the brain and the heart is exceptional. Here, we report a 11-year-old boy who was diagnosed to have two large hydatid cysts of the heart and brain. We discuss this unusual presentation of hydatid cyst and its management.

Prognostic Value of CD200 Expression and Soluble CTLA-4 Concentrations in Intermediate and High-Risk Myelodysplastic Syndrome Patients.

OBJECTIVE: This study was designed in order to identify the prognostic relevance of CD200 expression and soluble Cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in myelodysplastic syndrome (MDS) patients. METHODS: The study included 57 MDS (37 intermediate and 20 high risk) patients and 10 controls. For all of included patients; CD200 expression was identified by flowcytometry on CD33 positive cells and soluble CTLA-4 (CD152) concentration was determined by ELISA. RESULTS: CD200 positive expression was detected in 32/57 (56.1%) of MDS cases, the mean serum CTLA-4 concentrations were significantly higher in MDS patients as compared to controls (P<0.01). Significant association between high CD200 positive expression; high CTLA-4   concentration levels and   MDS risk stages being higher in high risk MDS group as compared to intermediate risk one (P < 0.01).  After 36-month follow-up; the subgroup of MDS patients with high expression of CD200; and high serum CTLA-4 concentrations showed high death rate and high frequency of acute myeloid leukemia transformation. CONCLUSIONS: CD200 positive expression could be considered as a new prognostic marker for risk stratification of MDS patients. CD200 expression may exert its effect through upregulation of CTLA-4.
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