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Mahmoud Abunasser,1– 3 Hala Abu-Fares,1 Sarah Abdel-Razeq,2 Omar Shamieh,2,3 Osama Salama,1 Khaled Ashouri,1 Abdullah Al Qudah,1 Ayat Taqash,4 Hala Abu-Jaish,5 Salwa S Saadah,1,2 Hikmat Abdel-Razeq1,2 1Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, the University of Jordan, Amman, Jordan; 3Department of Palliative Medicine, King Hussein Cancer Center, Amman, Jordan; 4Office of Scientific Affairs and Research, King Hussein Cancer Center, Amman, Jordan; 5School of Medicine, Jordan University of Science and Technology, Irbid, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, 202 Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman, 11941, Jordan, Tel +962-6 5300460, Ext: 1000, Email habdelrazeq@khcc.joBackground: Contrary to Western societies, more than 15% of patients with breast cancer in Jordan are diagnosed with stage IV disease. In this study, we evaluate the value of early palliative care integration in the end-of-life care of such patients.Methods: All consecutive adult patients who died between 2014 to 2018, while under the care of our institution, with a confirmed diagnosis of breast cancer at the time of death, irrespective of place of death, were retrospectively reviewed.Results: During the study period, a total of 433 patients, median age 51.6 years, were included in the analysis. Among the whole group, 102 (23.6%) were referred to palliative care service early (≥ 30 days prior to death), 182 (42.0%) had late referral (< 30 days from death), while 149 (34.4%) were never referred and were followed up by their medical oncologists. During the last 30 days prior to death, patients who were never referred to palliative care were more likely to visit the Emergency Room (ER) more than once (OR 1.89, 95% CI 1.20– 2.99, p = 0.006), more likely to be admitted to the hospital more than once (OR 2.27, 95% CI 1.38– 3.73, p = 0.001), and more likely to be admitted to the intensive care unit (ICU) (OR 3.07, 95% CI 1.48– 6.38, p = 0.0027). Fewer patients in the “no referral” group died with advance directives compared to those who had early or late referral; 60.8%, 75.0% and 82.5%, respectively, p = 0.0003. Survival of patients followed by medical oncologist was not better than those referred to palliative care, either late or early; median survival was 19.0, 19.1 and 23.8 months, respectively (p = 0.2338).Conclusion: Findings suggest that earlier palliative care referral is associated with less aggressive end-of-life care, leading to less frequent ER visits, hospital and ICU admissions during the last month of life, and does not compromise survival.Keywords: metastatic breast cancer, palliative care, end-of-life, Do not resuscitate, DNR

Baha’ Sharaf, Hala Abu-Fares, Faris Tamimi, Suhaib Al-Sawajneh, Osama Salama, Rand Daoud, Abdulrahman Alhajahjeh, Sawsan Al-Lababidi, Hikmat Abdel-Razeq Department of Internal Medicine, King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman, 11941, Jordan, Tel +962-6 5300460, Ext: 1000, Email habdelrazeq@khcc.joBackground: Metastatic breast cancers (MBC) with no expression of human epidermal growth factor receptor-2 (HER2) are recently classified into two groups; HER2-zero [HER2-immunohistochemistry (IHC) score of 0 (IHC-0)] and HER2-low, defined as those with IHC score of 1+ or 2+ with negative in situ hybridization (ISH) assay. We investigate differences in treatment outcomes between both groups treated with endocrine therapy (ET) and the CDK4/6 inhibitor ribociclib.Methods: Data were retrospectively collected for patients with HR-positive+/HER2−negative MBC who received ribociclib with an aromatase inhibitor (AI) or fulvestrant and were divided into two groups: HER2-zero and HER2-low.Results: A total of 257 patients, median age 48 (22– 87) years, all with MBC who were treated with ET and ribociclib were enrolled. One hundred and thirty-seven (53.3%) patients had de novo MBC, and majority (n = 162, 63.0%) received ribociclib as a first-line therapy. In total, 114 (44.4%) patients had HER2-zero (IHC-0), while 143 (55.6%) others had HER2-low disease. The overall response rate (ORR) was 52.0% for the HER2-zero group compared to 39.4% for the HER2-low group, p = 0.005. The median PFS was 22.2 (95% confidence interval [CI], 19.4-NR) months for HER2-zero versus 17.3 (95% CI, 14.1– 20.6) months for HER2-low, P = 0.0039. In multivariable analysis, HER2-low expression remained significant determinant of inferior PFS after adjusting for other factors, including the site of metastasis, prior chemotherapy, and the line of treatment.Conclusion: In patients with MBC treated with ET and ribociclib, level of HER2 negativity may affect treatment outcomes; patients with HER2-zero had better response rate and PFS compared to those with HER2-low disease. These findings, if confirmed in larger studies, may help oncologists select patients with HER2-low for better treatment options.Keywords: breast cancer, CDK4/6 inhibitors, endocrine therapy, HER2-low, HER2-zero

Hikmat Abdel-Razeq,1,2 Lama Abujamous,3 Khansa Al-Azzam,1 Hala Abu-Fares,1 Hira Bani Hani,1 Mais Alkyam,1 Baha’ Sharaf,1 Shatha Elemian,1 Faris Tamimi,1 Fawzi Abuhijla,4 Sarah Edaily,1 Osama Salama,1 Hazem Abdulelah,1 Rand Daoud,1 Mohammad Abubaker,1 Areej Al-Atary5 1Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, The University of Jordan, Amman, Jordan; 3Department of Cell Therapy & Applied Genomic, King Hussein Cancer Center, Amman, Jordan; 4Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan; 5Department of Nursing, King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, School of Medicine, University of Jordan, Queen Rania Al Abdullah Street, P.O. Box 1269, Amman, 11941, Jordan, Tel +962-6 5300460, Ext 1000, Email habdelrazeq@khcc.joBackground: Genetic testing for at-risk patients with breast cancer should be routinely offered. Knowledge generated may influence both treatment decisions and cancer prevention strategies among the patients themselves and their relatives. In this study, we report on the prevalence and patterns of germline mutations, using commercially available next-generation sequencing (NGS)-based multi-gene panels (MGP).Patients and Methods: Consecutive at-risk breast cancer patients, as determined by international guidelines, were offered germline genetic testing using a 20-gene NGS-based panel at a reference lab. Samples of peripheral blood were obtained for DNA extraction and genetic variants were classified as benign/likely benign (negative), pathogenic/likely pathogenic (positive) or variants of uncertain significance (VUS).Results: A total of 1310 patients, median age (range) 43 (19– 82) years, were enrolled. Age ≤ 45 years (n = 800, 61.1%) was the most common indication for testing. Positive family history of breast, ovarian, pancreatic or prostate cancers, and triple-negative disease were among the common indications. Among the whole group, 184 (14.0%) patients had pathogenic/likely pathogenic variants; only 90 (48.9%) were in BRCA1 or BRCA2, while 94 (51.9%) others had pathogenic variants in other genes; mostly in APC, TP53, CHEK2 and PALB2. Mutation rates were significantly higher among patients with positive family history (p = 0.009); especially if they were 50 years or younger at the time of breast cancer diagnosis (p < 0.001). Patients with triple-negative disease had relatively higher rate (17.5%), and mostly in BRCA1/2 genes (71.4%). Variants of uncertain significance (VUS) were reported in 559 (42.7%) patients; majority (90.7%) were in genes other than BRCA1 or BRCA2.Conclusion: Pathogenic mutations in genes other than BRCA1/2 are relatively common and could have been missed if genetic testing was restricted to BRCA1/2. The significantly high rate of VUS associated with multi-gene panel testing can be disturbing.Keywords: breast cancer, BRCA1, BRCA2, multigene panel, hereditary breast cancer, next generation sequencing

Hikmat Abdel-Razeq,1,2 Baha’ Sharaf,1 Rama AlMasri,3 Rashid Abdel-Razeq,1 Faris Tamimi,1 Omar Khader,1 Osama Salama,1 Mahmoud Abunasser,1 Sarah Edaily,1 Hazem Abdulelah1 1Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan; 2Department of Internal Medicine, School of Medicine, The University of Jordan, Amman, Jordan; 3Department of Internal Medicine, Istishari Hospital, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, 202 Queen Rania Al Abdullah Street, Amman, Jordan, Tel +962 79 643 3993, Fax +962 6 535 3001, Email habdelrazeq@khcc.joPurpose: Cyclin dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) modulate endocrine resistance and are integral treatment for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Since their approval, CDK4/6 inhibitors are widely used in clinical practice. Thromboembolic events (TEE) were not a major issue in patients treated on clinical trials utilizing these agents. However, conflicting data started to emerge describing higher than expected rates of both arterial and venous thrombosis in patients treated with CDK4/6 inhibitors. In this study, we report our experience on TEE in patients treated with one of these agents (ribociclib) in real-world settings.Patients and Methods: All consecutive patients with metastatic breast cancer (mBC) treated with ribociclib combined with letrozole or fulvestrant were retrospectively reviewed. All episodes of radiologically confirmed arterial or venous thrombosis were recorded. TEE was considered ribociclib-related if diagnosed while patients are on the drug, or within 4 weeks after the last dose.Results: A total of 305 patients, median age (range), 49 (22– 87) years were enrolled. All patients had metastatic disease, and most (n=241, 79.0%) were with visceral metastasis. Ribociclib was used for a median duration of 7 months (range: 1– 45) and was used beyond the first-line setting in 110 (35.9%) patients. TEE were confirmed on 6 (1.97%) patients; 3 were pulmonary embolism, 2 cerebral venous sinus thrombosis (CVST), and one case of limb ischemia and all were symptomatic. Similar rates of TEE were noted prior to initiation, and after stopping ribociclib.Conclusion: In real-world settings, breast cancer patients treated with ribociclib, combined with aromatase inhibitors or fulvestrant, may not be at higher risk for thromboembolic events. However, unusual sites of thrombosis, like CVST, may raise some concerns.Keywords: CDK4/6 inhibitors, letrozole, fulvestrant, thrombosis, patient stratification, prediction

Baha’ Sharaf,1 Rama AlMasri,2 Nayef Abdel-Razeq,3 Osama Salama,1 Ibrahim Hamad,1 Mahmoud Abunasser,1 Hikmat Abdel-Razeq1,4 1Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan; 2Department of Internal Medicine, Istishari Hospital, Amman, Jordan; 3Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA; 4School of Medicine, University of Jordan, Amman, JordanCorrespondence: Hikmat Abdel-RazeqDepartment of Internal Medicine, King Hussein Cancer Center, School of Medicine, University of Jordan, Queen Rania Al Abdullah Street, PO Box 1269, Amman 11941, JordanTel + 962-6 5300460, Ext: 1000Email habdelrazeq@khcc.joBackground: Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer, with an impressive efficacy and safety profile. Cytopenia is the main adverse event, which is both predictable and manageable. Here, we report a case of CDK4/6 inhibitor-induced vitiligo-like lesions. Vitiligo or vitiligo-like lesions are a rare adverse event; only a few cases are reported in the literature.Case Presentation: A 71-year-old female patient was diagnosed initially with early-stage right breast cancer (HR+/HER2−) and was treated with breast-conserving surgery followed by chemotherapy, radiotherapy, and hormonal therapy. A few years later, she developed metastatic disease to the hilar lymph nodes, and to multiple skeletal sites, including the left scapula, left shoulder, left iliac bone, and dorsal vertebrae, for which she was treated with ribociclib and letrozole. While on treatment, she developed hypopigmented lesions involving both hands, feet, and face, which were described as vitiligo-like lesions.Conclusion: CDK4/6 inhibitor-induced vitiligo is a rare and unpredictable adverse event. This case report highlights the rarity of this adverse event, the dilemma related to the optimal treatment, and decisions related to continuation, holding, or switching CDK4/6 inhibitors.Keywords: CDK4/6 inhibitors, ribociclib, vitiligo, vitiligo-like, breast cancer, skin adverse events

Hikmat Abdel-Razeq,1,2 Faris Tamimi,1 Lama Abujamous,3 Sara Edaily,1 Mahmoud Abunasser,1 Rayan Bater,1 Osama Salama1 1Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan; 2Department of Internal Medicine, School of Medicine, University of Jordan, Amman, Jordan; 3Department of Cell Therapy & Applied Genomic, King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-RazeqDepartment of Internal Medicine, King Hussein Cancer Center, Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman, 11941, JordanTel +962-6 5300460, Ext: 1000Email habdelrazeq@khcc.joBackground: Among all subtypes, patients with triple-negative (TN) breast cancer is known for their poor outcome and their higher risk of harboring BRCA1 or BRCA2 pathogenic mutations. Identification of such mutations has clinical impact on breast and ovarian cancer prevention and treatment decisions. We here report on patterns and prevalence of BRCA1 and BRCA2 mutations among Arab patients diagnosed with TN subtype.Patients and Methods: Patients with TN-breast cancer (n=197) were enrolled regardless of their age or family history. Following a detailed genetic counseling, BRCA1/2 testing was performed at reference labs. BRCA1 and BRCA2 variants were classified as negative, pathogenic/likely pathogenic (positive) and variants of uncertain significance (VUS).Results: Median age of enrolled patients was 42 (range, 19– 74) years and 27 (13.7%) were non-Jordanian Arabs. Among the study group, 50 (25.4%) were tested positive for BRCA1 (n=36, 18.3%) or BRCA2 (n=14, 7.1%), while 14 (7.1%) others had VUS. Compared to older ones, mutation rates were higher among patients < 40 years (32.9%, P= 0.034), those with close relatives with breast, ovarian, pancreatic or prostate cancer (37.8%, P=0.002) and those with two or more breast cancers (41.4%, P=0.032). Among eligible patients, 23 (63.9%) patients underwent prophylactic mastectomy, while 19 (52.8%) patients had risk-reducing salpingo-oophorectomy. None of the patients with VUS underwent any prophylactic surgery.Conclusion: Arab patients with TN-breast cancer have relatively high BRCA1 or BRCA2 mutation rates. Young age at diagnosis and personal and family history of breast cancer further increase this risk.Keywords: cancer genetics, genetic consultation, genetic variants, women’s cancer, breast cancer, BRCA1/2 mutation

Omar Hassan Salama,1 Ezzat Nabil Abbas Ibrahim,1 Mostafa Osman Hussein,1 Ahmed Mohammed Madinah Alkady,1 Mohammed Eid Abd El-Salam,1 Saad Ghanem2 1Ophthalmology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 2Rheumatology and Rehabilitation Department, Faculty of Medicine, Al-Azhar University, Cairo, EgyptCorrespondence: Omar Hassan Salama, Lecturer of Ophthalmology, Faculty of Medicine, Al Azhar University, El Hussain University Hospital, Gawhar Al Qaed Street, Al Darrasah, Cairo, 11561, Egypt, Tel +201146316323, Email omar.salama@azhar.edu.egPurpose: To report clinical, serological, and histopathological findings in Egyptian patients with dacryoadenitis associated with ImmunoglobulinG4-related disease (IgG4-RD).Methods: We retrospectively revised medical records of patients presented to Al-Azhar University Hospitals with lacrimal gland (LG) swelling between June 2016 and February 2022. We included patients with definite IgG4-related disease (IgG4-RD) diagnosis and excluded those with possible, probable, or unlikely IgG4-RD based on The Japanese Ministry of Health, Labour, and Welfare’s 2011 guidelines.Results: Sixteen cases were included in the study (Fourteen females and two males, mean age 39.2± 12.2 years); Seven cases met the criteria of Mikulicz disease, and nine cases met full clinical, serological, and histopathological criteria. Mean reported serum IgG was 1792.5 ± 313.7 (range 1063– 2134) mg/dl, mean serum IgG4 was 576.25± 215.3 (range 112– 841) mg/dl, and mean Serum IgG4/IgG ratio was 31.9 ± 12.4%. The mean number of IgG4+ plasma cells/HPF was 74 ± 21.2, and the mean IgG4+ plasma cell percentage was 55 ± 9.7%. Serum IgG4 level showed a positive correlation to tissue IgG4+plasma cell percentage, while serum IgG4/IgG ratio positively correlated to both percentage and number of IgG4+plasma cells. Steroids had a good initial response, but recurrences were common.Conclusion: A considerable proportion of patients with lacrimal gland swelling fall within the range of IgG4-RD. Proper diagnosis requires clinical, serological, and histopathologic correlation. Patients require long follow-up periods.Keywords: IgG4-RD, IgG4-ROD, IgG4-related dacryoadenitis, Mikulicz disease

LC-ESI-MS/MS was used for a comprehensive characterisation of ethanol extract from the leaves of three Pistacia species. After optimisation of the method and the use of the negative ionisation mode, a total of 42 different compounds were identified, of which 22 were tentatively characterised in P. chinensis Bunge, 33 in P. khinjuk stocks and 25 in P. lentiscus L. leaves. Flavonoids, phenolic acids, and their derivatives were the most abundant identified compounds. LC-ESI-MS/MS revealed identification of 15, 18 and 6 not previously detected compounds in P. chinensis Bunge, P. khinjuk Stocks and P. lentiscus L., respectively. The three extracts were also tested for their cytotoxic activities against human PC3 prostate cancer, A549 lung cancer, MCF7 breast cancer and HepG2 liver cancer. Generally, all the extracts have a moderate cytotoxic activity against lung, breast and prostate cancer, with different IC50. However, only P. lentiscus L. showed moderate activity against liver cancer. [ABSTRACT FROM AUTHOR]

This work proposes an advanced control of power converters used in photovoltaic solar energy. The boost converter and NPC three level inverter are usually associated with photovoltaic cells. A maximum power point tracking algorithm is adopted in this case to maximize the output power by using the sliding mode control approach. For three level inverter, five command strategy is applied in order to compare their performances: PDPWM (Phase Disposition PWM), PODPWM (Phase Opposition Disposition PWM), APODPWM (Alternative Phase Opposition Disposition PWM), COPWM (Carrier Overlapping PWM), PSPWM (Phase Shift PWM). The total harmonic distortion (THD) is evaluated for the various modulation index. Finally, validity and effectiveness are verified through a simulation in Matlab/Simulink. [ABSTRACT FROM AUTHOR]

Objectives. Helicobacter pylori (H. pylori) is a common gastric infection associated with extragastric conditions. The association between H. pylori infection and obesity is unclear. H. pylori may affect gut hormones involved in food intake and energy expenditure. The aim of this study is to evaluate ghrelin/obestatin balance and leptin in obese subjects with H. pylori infection.

Abstract This study was designed to evaluate the ability of MALDI Biotyper (MBT) compared with Vitek™ 2 compact system for accurate identification of Staphylococcus aureus (S. aureus) and coagulase‐negative staphylococci (CNS) strains and discriminate methicillin‐sensitive S. aureus (MSSA) from methicillin‐resistant S. aureus (MRSA). Throughout Al‐Qassim region, Saudi Arabia, a total of 198 isolates of S. aureus (132 MSSA and 66 MRSA) and 44 CNS were collected from five dairy farms where the prevalence of staphylococcal mastitis was reported. The results produced by Vitek™ 2 compact system demonstrated that 123/132 MSSA isolates (93.18%), 61/66 MRSA (92.42%), and 37/44 CNS species (84.09%) were correctly identified. However; 130/132 MSSA (98.48%), 64/66 MRSA (96.96%), and 44/44 CNS (100%) were correctly identified by MBT with score ≥2. 00. The principal component analysis (PCA) dendrogram generated by MBT illustrated that the tested isolates were classified into two groups of Staphylococcus species at the distance level of 600. S. aureus isolates were found to be closely related with higher peak intensities in the mass of 3,993 Da, 4,121 Da and 5,845 Da were detected in MRSA, whereas, that were lost in MSSA. Conclusion: This study verified that MBT is an alternative powerful tool for precise identification and discrimination of Staphylococcus species.

IgG and IgM anticardiolipin antibody (Ab) concentrations were determined in serum samples of 48 children with end-stage renal disease (ESRD) on haemodialysis using ELISA technique in an attempt to analyse their possible role in the occurrence of thrombosis of the vascular access. Ten normal healthy children were studied as a control group. The positivity of anticardiolipin Ab isotypes both IgM and IgG was high in children with ESRD on haemodialysis. Children with positive anticardiolipin Ab had significantly higher incidence of prior thrombosis of vascular access. Also, these antibodies should be considered as markers of high risk for fistula thrombosis. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Brucellosis is a neglected tropical zoonosis allegedly reemerging in Middle Eastern countries. Infected ruminants are the primary source of human infection; consequently, estimates of the frequency of ruminant brucellosis are useful elements for building effective control strategies. Unfortunately, these estimates are lacking in most Middle East countries including Egypt. Our objectives are to estimate the frequency of ruminant brucellosis and to describe its spatial distribution in Kafr El Sheikh Governorate, Nile Delta, Egypt. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional study in which 791 sheep, 383 goats, 188 cattle milk tanks and 173 buffalo milk tanks were randomly selected in 40 villages and tested for the presence of antibodies against Brucella spp. The seroprevalence among different species was estimated and visualized using choropleth maps. A spatial scanning method was used to identify areas with significantly higher proportions of seropositive flocks and milk tanks. We estimated that 12.2% of sheep and 11.3% of goats in the study area were seropositive against Brucella spp. and that 12.2% and 12% of cattle and buffalo milk tanks had antibodies against Brucella spp. The southern part of the governorate had the highest seroprevalence with significant spatial clustering of seropositive flocks in the proximity of its capital and around the main animal markets. CONCLUSIONS/ SIGNIFICANCE: Our study revealed that brucellosis is endemic at high levels in all ruminant species in the study area and questions the efficacy of the control measures in place. The high intensity of infection transmission among ruminants combined with high livestock and human density and widespread marketing of unpasteurized milk and dairy products may explain why Egypt has one of the highest rates of human brucellosis worldwide. An effective integrated human-animal brucellosis control strategy is urgently needed. If resources are not sufficient for nationwide implementation, high-risk areas could be prioritized.