Crop microbiome: their role and advances in molecular and omic techniques for the sustenance of agriculture.

MAIN CONCLUSION: This review is an effort to provide in-depth knowledge of microbe's interaction and its role in crop microbiome using combination of advanced molecular and OMICS technology to translate this information for the sustenance of agriculture. Increasing population, climate change and exhaustive agricultural practices either influenced nutrient inputs of soil or generating biological and physico-chemical deterioration of the soils and affecting the agricultural productivity and agro-ecosystems. Alarming concerns toward food security and crop production claim for renewed attention in microbe-based farming practices. Microbes are omnipresent (soil, water, and air) and their close association with plants would help to accomplish sustainable agriculture goals. In the last few decades, the search for beneficial microbes in crop production, soil fertilization, disease management, and plant growth promotion is the thirst for eco-friendly agriculture. The crop microbiome opens new paths to utilize beneficial microbes and manage pathogenic microbes through integrated advanced biotechnology. The crop microbiome helps plants acquire nutrients, growth, resilience against phytopathogens, and tolerance to abiotic stresses, such as heat, drought, and salinity. Despite the emergent functionality of the crop microbiome as a complicated constituent of the plant fitness, our understanding of how the functionality of microbiome influenced by numerous factors including genotype of host, climatic conditions, mobilization of minerals, soil composition, nutrient availability, interaction between nexus of microbes, and interactions with other external microbiomes is partially understood. However, the structure, composition, dynamics, and functional contribution of such cultured and uncultured crop microbiome are least explored. The advanced biotechnological approaches are efficient tools for acquiring the information required to investigate the microbiome and extract data to develop high yield producing and resistant variety crops. This knowledge fills the fundamental gap between the theoretical concepts and the operational use of these advanced tools in crop microbiome studies. Here, we review (1) structure and composition of crop microbiome, (2) microbiome-mediated role associated with crops fitness, (3) Molecular and -omics techniques for exploration of crop microbiome, and (4) current approaches and future prospectives of crop microbiome and its exploitation for sustainable agriculture. Recent -omic approaches are influential tool for mapping, monitoring, modeling, and management of crops microbiome. Identification of crop microbiome, using system biology and rhizho-engineering, can help to develop future bioformulations for disease management, reclamation of stressed agro-ecosystems, and improved productivity of crops. Nano-system approaches combined with triggering molecules of crop microbiome can help in designing of nano-biofertilizers and nano-biopesticides. This combination has numerous merits over the traditional bioinoculants. They stimulate various defense mechanisms in plants facing stress conditions; provide bioavailability of nutrients in the soil, helps mitigate stress conditions; and enhance chances of crops establishment.

Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women.

PURPOSE: BRCA gene mutations (BRCAm) have an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. METHODS: This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). RESULT: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. CONCLUSION: The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. TRIAL REGISTRATION: Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Levels of residues and dietary risk assessment of the fungicides myclobutanil, penconazole, tebuconazole, and triadimenol in squash.

Triazole fungicides may potentially harm human health. The 'quick, easy, cheap, effective, rugged, and safe' approach has become popular for extraction and cleanup during pesticide residue analysis. We aimed to (a) validate a method for the simultaneous determination of myclobutanil, penconazole, tebuconazole, and triadimenol in squash using LC-MS/MS and (b) determine the pre-harvest intervals (PHIs) and assess the related risk of consuming squash cultivated under open-field conditions in Saudi Arabia. Using acetonitrile as the extraction solvent and fourfold dilution in deionized water led to weak signal suppression (<-6.1%). The limits of quantitation ranged from 10 to 40 µg/kg. Mean recovery and relative standard deviation ranged from 81.7 to 96.3% and from 3.6 to 11.4%. The half-lives ranged from 2.22 to 3.83 days, and the dissipation followed first-order kinetics. The terminal residues of myclobutanil, penconazole, tebuconazole, and triadimenol were <0.771, <0.307, <0.459, and <0.954 mg/kg, respectively, 7 days after two or three applications of recommended dosages. The PHIs of 7.1-11.4, 8.7-13.1, 3.8-5.3, and 11.3-14.3 days are suggested after the application of the recommended dose and double the recommended dose. A consumer risk assessment based on estimated dietary intake indicated that the consumption of squash treated with the recommended doses does not pose a significant health risk.

Clinicopathological significance of the immunologic signature (PDL1, FOXP3+ Tregs, TILs) in early stage triple-negative breast cancer treated with neoadjuvant chemotherapy.

Patients with breast cancer are appropriate candidates for neoadjuvant chemotherapy (NAC) to facilitate conservative surgery. The chemotherapeutic agents may exert their action by inducing the anti-tumor immune response. This study aimed to evaluate the tumor immune microenvironment including PD-L1, Foxp3+ Tregs, and TILs count in early stages TNBC patients (stage T1, T2) before and after neoadjuvant chemotherapy and their correlation with the clinical and pathological response. Fifty patients of TNBC patients were enrolled in this study; all of them received neoadjuvant chemotherapy. TILs count, Foxp3+ Tregs, and PD-L1 immunohistochemical expression were investigated in all cases before NAC and then evaluated in residual masses after surgery. Data on the clinical and pathological response to NAC were collected and then statistically analyzed. PDL1 expression was detected in 24% of all studied cases, all of them were node-positive (P < 0.002); while Foxp3+ Tregs expressed in 50% and high TILs in 28%. Pathological complete response (pCR) was achieved in 40% of patients and was associated with high TILs expression (P < 0.02) and absence of Foxp3+ Tregs and PDL1 (P < 0.001 for each). In conclusion, Pathologic complete response to NAC was associated with the immunological profile of TNBC. High TILs expression with concomitant decreased PD-L1 expression and low FOXP3+ Tregs is associated with favorable tumor prognosis. Combined therapeutic approaches aiming to PD-L1 block and Tregs depletion might improve treatment efficacy in TNBC.

Potato purple top disease associated with the novel subgroup 16SrII-X phytoplasma.

Potato (Solanum tuberosum) is a very economically important perennial tuberous crop in Saudi Arabia. Potato plants displaying symptoms associated with potato purple top disease, such as aerial tubers and purple and small leaves, were observed in Al-Bukairiyah, Fowlq and Buraydah, Al-Tarafiyah, Qassim governorate, Saudi Arabia. In this study, we examined samples taken from 12 symptomatic potato plants and confirmed the presence of phytoplasma DNA. Analysis of the 16S rRNA-encoding sequences revealed that the symptomatic plants were infected with phytoplasma belonging to the peanut witches'-broom group (16SrII). Sequencing of the 16S rRNA- encoding gene, computer-simulated RFLP analysis and phylogenetic analysis revealed the presence of a novel representative of the 16SrII-X subgroup. The present study identified potato plants as a novel host for novel phytoplasma strains belonging to the pigeon pea witches'-broom group in Saudi Arabia.

Molecular identification and characterization of the new 16SrIX-J and cpn60 UT IX-J phytoplasma subgroup associated with chicory bushy stunt disease in Saudi Arabia.

Chicory (Cichorium intybus) is a perennial plant (Asteraceae) that grows wild in pasture fields in Saudi Arabia. Chicory plants displaying symptoms typically induced by phytoplasmas, such as bushy phenotype and stunt, were observed in the Mulayda region, Qassim governorate, Saudi Arabia. In this study we examined samples taken from three symptomatic chicory plants and confirmed the presence of phytoplasma DNA. Analysis of the 16S rRNA-encoding sequences showed that the plants were infected with a phytoplasma from the pigeon pea witches'-broom group (16SrIX). Sequencing of the 16S rRNA-encoding gene and the partial cpn60 sequence, computer-simulated RFLP analysis, and phylogenetic analysis of both markers revealed that the phytoplasma identified was representative of a new 16SrIX-J and cpn60 UT IX-IJ subgroup. The present study identified chicory plants as a novel host for phytoplasma strains within the pigeon pea witches'-broom phytoplasma group, and expanded the known diversity of this group.

A rare case of duplicated vas deferens discovered accidentally during varicocelectomy.

Congenital anomalies of the male urogenital tract include a variety of structural abnormalities. These abnormalities could affect either the male external genitalia, internal genitalia or both. Congenital anomalies of the vas deferens are rare and may include unilateral or bilateral (agenesis, atresia, duplication, ectopy or diverticulum) that could be complete or segmental. In addition, they may be isolated anomalies of the vas deferens or may be associated with other congenital anomalies elsewhere especially in the male urogenital tract. Those anomalies may be discovered during genital examination (either clinically or radiologically) or even during inguinal surgeries as in hernia repair, vasectomy, orchiopexy and varicocelectomy. Thus, proper evaluation should be made for the cases of duplicated vas deferens to avoid the accidental injury during the operation and to exclude other associated congenital anomalies. Besides that, the undiagnosed cases may lead to failure of vasectomy procedure. Here, we report a case of duplication of the vas deferens in a 33-year-old male that was accidentally discovered during spermatic cord dissection for varicocelectomy.

Prostate cancer across four countries in the Middle East: a multi-centre, observational, retrospective and prognostic study.

Prostate cancer (PC) is the second most prevalent cancer in males, with a steadily increasing incidence in the Middle East (ME). The aim of this study was to capture real-world data on the characteristics, disease progression, and treatment patterns among PC patients in the ME. This was a retrospective, observational, multi-centre study conducted across ten hospitals/research centers in Lebanon, Kingdom of Saudi Arabia, Iraq and Kuwait. Data were abstracted from medical records of 615 male patients who were diagnosed with PC between January 2012 and the site initiation date (December 2018-May 2019) and received at least one PC treatment/intervention. The observation period ranged between 84 and 88 months. Data were collected on demographics, clinical characteristics, time to progression to the subsequent clinical state or therapy (progression from localised/locally advanced PC to castration and to metastatic PC (metastatic castration-sensitive PC (mCSPC) or metastatic castration-resistant PC (mCRPC)), progression from mCSPC to mCRPC, and mCRPC patients' progression to first subsequent line of therapy), treatment patterns, and mortality. Most patients had localised/locally advanced PC (57.7%), followed by mCSPC (37.4%), and mCRPC (4.1%) at the time of inclusion in the study. Most patients were at tumours, nodes and metastases (TNM) stage IIIa (40.1%) or TNM stage IVb (27.8%) at study entry. Median time to metastatic disease, castration-resistance and next line therapy was 84 months (95% CI: 68-84), 41 months (95% CI: 30-56) and 7 months (95% CI: 0-41), respectively. The mortality rate was 3.6%. Disease progression was most common among patients with mCSPC (35.1%) or mCRPC (14.8%), and treatment discontinuation was most common among patients with mCRPC (36.6% treatments discontinued). The results show that most patients were at an advanced TNM stage at study entry, suggestive of a lack of awareness regarding PC. Disease progression was most common among patients with metastatic disease, reflecting the challenge of treating metastatic disease and highlighting the need for novel treatments.

Recent advances in PGPR-mediated resilience toward interactive effects of drought and salt stress in plants.

The present crisis at hand revolves around the need to enhance plant resilience to various environmental stresses, including abiotic and biotic stresses, to ensure sustainable agriculture and mitigate the impact of climate change on crop production. One such promising approach is the utilization of plant growth-promoting rhizobacteria (PGPR) to mediate plant resilience to these stresses. Plants are constantly exposed to various stress factors, such as drought, salinity, pathogens, and nutrient deficiencies, which can significantly reduce crop yield and quality. The PGPR are beneficial microbes that reside in the rhizosphere of plants and have been shown to positively influence plant growth and stress tolerance through various mechanisms, including nutrient solubilization, phytohormone production, and induction of systemic resistance. The review comprehensively examines the various mechanisms through which PGPR promotes plant resilience, including nutrient acquisition, hormonal regulation, and defense induction, focusing on recent research findings. The advancements made in the field of PGPR-mediated resilience through multi-omics approaches (viz., genomics, transcriptomics, proteomics, and metabolomics) to unravel the intricate interactions between PGPR and plants have been discussed including their molecular pathways involved in stress tolerance. Besides, the review also emphasizes the importance of continued research and implementation of PGPR-based strategies to address the pressing challenges facing global food security including commercialization of PGPR-based bio-formulations for sustainable agricultural.

Performance of Plant-Growth-Promoting Rhizobacteria (PGPR) Isolated from Sandy Soil on Growth of Tomato (Solanum lycopersicum L.).

The plant-growth-promoting rhizobacteria (PGPR) in the rhizosphere affect plant growth, health, and productivity, as well as soil-nutrient contents. They are considered a green and eco-friendly technology that will reduce chemical-fertilizer usage, thereby reducing production costs and protecting the environment. Out of 58 bacterial strains isolated in Qassim, Saudi Arabia, four strains were identified by the 16S rRNA as the Streptomyces cinereoruber strain P6-4, Priestia megaterium strain P12, Rossellomorea aquimaris strain P22-2, and Pseudomonas plecoglossicida strain P24. The plant-growth-promoting (PGP) features of the identified bacteria involving inorganic phosphate (P) solubilization, the production of indole acetic acid (IAA), and siderophore secretion were assessed in vitro. Regarding the P solubilization, the previous strains' efficacy reached 37.71%, 52.84%, 94.31%, and 64.20%, respectively. The strains produced considerable amounts of IAA (69.82, 251.70, 236.57, and 101.94 µg/mL) after 4 days of incubation at 30 °C. Furthermore, the rates of siderophore production reached 35.51, 26.37, 26.37, and 23.84 psu, respectively, in the same strains. The application of the selected strains in the presence of rock phosphate (RP) with tomato plants under greenhouse conditions was evaluated. The plant growth and P-uptake traits positively and significantly increased in response to all the bacterial treatments, except for some traits, such as plant height, number of leaves, and leaf DM at 21 DAT, compared to the negative control (rock phosphate, T2). Notably, the P. megaterium strain P12 (T4), followed by R. aquimaris strain P22-2 (T5), revealed the best values related to plant height (at 45 DAT), number of leaves per plant (at 45 DAT), root length, leaf area, leaf-P uptake, stem P uptake, and total plant P uptake compared to the rock phosphate. The first two components of the PCA (principal component analysis) represented 71.99% (PCA1 = 50.81% and PCA2 = 21.18%) of the variation at 45 DAT. Finally, the PGPR improved the vegetative-growth traits of the tomato plants through P solubilization, IAA, and siderophore production, and ameliorated the availability of nutrients. Thus, applying in PGPR in sustainable agriculture will potentially reduce production costs and protect the environment from contamination by chemical fertilizers and pesticides.

Status migrainosus as a potential stressor leading to takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy is a form of non-ischemic cardiomyopathy that may be acutely precipitated by stress. A number of neurologic conditions have been implicated in precipitating this disease such as subarachnoid hemorrhage, stroke, and seizures. Its association with status migrainosus, however, has never been described before. CASE: We report a case of a 25-year-old female presenting with status migrainosus followed by takotsubo cardiomyopathy. Supportive management was instituted in this patient and she made an excellent recovery. CONCLUSION: The intense pain associated with migraine may have acted as a stressor, thereby precipitating takotsubo cardiomyopathy. To our knowledge, this is the first reported case demonstrating a relationship between status migrainosus and takotsubo cardiomyopathy.

Adult-Type Ovarian Granulosa Cell Tumour: Treatment Outcomes From a Single-Institution Experience.

OBJECTIVES:  Ovarian granulosa cell tumour is rare. This study aims to report the clinical characteristics and long-term outcomes of adult-type ovarian granulosa cell tumour (AOGCT) at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and to determine the prognostic factors affecting relapse and survival. METHODS: We retrospectively reviewed patients with AOGCT, from 1988 to 2014, who were treated at our institution. Baseline characteristics, pathological findings, and outcomes were analysed and reported. RESULTS: Sixty-one patients with AOGCT were identified with a median age of 49 years. Median follow-up was 5.0 years (range 2.1-8.2 years). 74% of patients were FIGO (International Federation of Gynecology and Obstetrics) stage I, whereas 7% were stage II, 5% were stage III, and unknown in 14% of the cases. The most common presenting symptoms included abdominal pain (43%) and vaginal bleeding (43%). The majority of patients (38 patients, 62%) were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Five (8%) patients received adjuvant chemotherapy. Sixteen patients (26%) relapsed with a median time to relapse of 5.5 years (0.7-8.1 years). Half of the recurrences (eight patients, 50%) occurred after five years of diagnosis. Five-year overall survival and disease-free survival (DFS) were 93% and 84%, respectively. Factors associated with a high risk of recurrence were the presence of ascites (p=0.000) and elevated preoperative CA 125 level (p=0.048). The overall survival was significantly influenced by the menopausal status (premenopausal 100% vs. postmenopausal 84%; p=0.02), preoperative CA 125 (normal 100% vs. elevated 64%; p=0.005), ascites (present 33% vs. absent 100%; p=0.000), and age (<55 years 100% vs. ≥ 55 years 77%; p= 0.002). CONCLUSION:  This study confirms a good outcome for patients with AOGCT. They require long-term follow-up as late recurrences can occur many years post definitive therapy. The presence of ascites and elevated preoperative CA 125 levels were associated with a higher risk of recurrence and poor prognosis. Outcomes appear unaffected by fertility-sparing surgery or adjuvant chemotherapy.

Exploring the Plant Growth-Promotion of Four Streptomyces Strains from Rhizosphere Soil to Enhance Cucumber Growth and Yield.

The genus Streptomyces is the most abundant and essential microbes in the soil microbial community. Streptomyces are familiar and have great potential to produce a large variety of bioactive compounds. This genus considers an efficient biofertilizer based on its plant growth-promoting activities. Based on their ability to produce a wide varieties of bioactive molecules, the present study aimed to explore the potential plant growth promotion of four Streptomyces strains and their role in enhancing cucumber growth and yield under greenhouse conditions. Streptomyces sp. strain HM2, Streptomyces thinghirensis strain HM3, Streptomyces sp. strain HM8, and Streptomyces tricolor strain HM10 were chosen for the current study. Plant growth-promoting (PGP) features, i.e., indole acetic acid (IAA) production, siderophore excretion, and solubilizing phosphate, were evaluated in vitro. All four strains produced IAA, siderophore, and immobilized inorganic phosphate. Following 4 days of incubation at 30 °C, strains HM2, HM3, HM8, and HM10 produced copious amounts of IAA (18, 22, 62, and 146 µg/mL, respectively) and siderophores (42.59, 40.01, 16.84, 64.14% SU, respectively). At the same time, P solubilization efficacy scored 64.3%, 84.4%, 57.2%, and 81.6% with the same frequency. During in planta evaluation, selected Streptomyces strains combined with rock phosphate were assessed as biofertilizers on the growth and yield of cucumber plants. Under all treatments, positive and significant differences in studied traits were manifested except dry stem matter (SDM), net assimilation rate (NAR), relative growth rate (RGR), and fruit firmness (FF). Treatment T4 (rock phosphate + strain HM3) followed by T5 (rock phosphate + strain HM8) revealed the best results for plant height (PH), number of leaves per plant (NLPP), root length (RL), number of fruits per plant (NFPP), fruit length (FL), fruit diameter (FD), fruit fresh weight per plant (FFWPP), soil P (SP) after 21 DAT, and soil P at the end of the experiment. Notably, T6 (rock phosphate + strain HM10) caused a considerable increase in leaf area (LA). Plant growth-promoting bacteria enhance plant growth and yield through phosphorus solubilizing, improve nutrient availability, produce phytohormones, and support plant growth under abiotic stress. These features are important for sustainable agriculture and reducing environmental pollution with chemical fertilizers and pesticides.

Impact of Pathologic Complete Response following Neoadjuvant Chemotherapy ± Trastuzumab in Locally Advanced Breast Cancer.

PURPOSE: This study was designed to examine the relationship between breast cancer molecular subtypes and pathological response to neoadjuvant chemotherapy (NAC) ± trastuzumab, in locally advanced breast cancer (LABC). METHODS: Female patients with LABC (T2-T4, N0-N2, and M0) who received neoadjuvant chemotherapy + trastuzumab if HER2+ subtype, followed by surgery and radiotherapy ± hormonal therapy, were identified. The primary endpoint was pathologic complete response (pCR) in the breast and axilla (ypT0/ypN0), with final analysis on disease-free survival (DFS) and overall survival (OS). RESULTS: Six hundred eighty-one patients with a median age of 44 years, premenopausal: 70%, median tumour size: 7.0 cm (range 4-11 cm), stage II B: 27% and III A/III B: 73%, ER+/HER2-: 40.8%, ER-/HER2-: 23%, ER+/HER2+: 17.7%, and ER-/HER2+: 18.5%. Overall pCR (ypT0/ypN0) was 23%. The pCR rates based on molecular subtypes were ER+/HER2-: 9%; ER+/HER2+: 29%; ER-/HER2-: 31%; and ER-/HER2+: 37%. At median follow-up of 61 months, ER+/HER2+ and ER+/HER2- subtypes had the best 5-year DFS and OS; meanwhile, ER-/HER2+ and ER-/HER2- subtypes had the worst. CONCLUSION: Women with ER+/HER2- disease are the least likely to achieve pCR, with the highest rates in HER2+ and triple-negative subgroups. Degree of response is associated with OS; despite the comparatively higher likelihood of achieving pCR in ER-/HER2+ and triple-negative, these subgroups experience a survival detriment. We are consistent with the published data that patients who attain the pathological complete response defined as ypT0/ypN0 have improved outcomes.

Trastuzumab, Pertuzumab, and Docetaxel as the First Line for HER-2-Positive Metastatic Breast Cancer among Arabs.

INTRODUCTION: Human epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits. OBJECTIVE: We evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population. PATIENTS AND METHODS: We identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013-2016. RESULTS: Median age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6-48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference. CONCLUSIONS: First line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.

Effect of KRAS mutational status on disease behavior and treatment outcome in patients with metastatic colorectal cancer: intratumor heterogeneity and mutational status.

BACKGROUND: Nowadays, the outcomes of metastatic colorectal cancer (mCRC) have considerably improved. Genetic studies evaluating KRAS mutational status are important in the personalized therapy era to understand disease heterogeneity, disease behaviors, and treatment outcomes. METHODS: This multicenter retrospective study evaluated 360 patients with mCRC treated at three oncology centers in Saudi Arabia and Egypt between February 2011 and December 2015. Patients were treated with bevacizumab and cetuximab according to guidelines. Therapy outcome, time to progression, and disease-associated death were assessed. KRAS mutational status was evaluated by testing exons 12 and 13. RESULTS: Approximately 220 (61.1%) cases were of wild-type KRAS, whereas KRAS mutation was noted in 38.9%. KRAS mutation was common in the descending colon, whereas a low incidence of the KRAS mutation was observed in the ascending colon (P<0.001). Among patients with KRAS mutation, 64.3% initially presented as emergency cases with obstruction/perforation (P=0.002), and 62.9% had hepatic or pulmonary metastasis. The progression-free survival (PFS) was 10.7 months. Cases without KRAS mutation showed a higher PFS than did those with KRAS mutation (mean PFS: 11.5 vs. 9.6 months, P=0.001). The overall survival was 23.2 months. The survival varied considerably according to KRAS type: patients without mutation survived for 25.0 months and those with mutation survived for 19.6 months (P<0.001). Disease-related death occurred in 132 (36.7%) cases, approximately 57.1% of them (80 cases) had KRAS mutations (P=0.001). CONCLUSIONS: A major association between KRAS mutational status and both disease behavior and treatment outcomes was found in this study. Patients with KRAS mutation show advanced disease presentation, with lower PFS and overall survival.

The Significance of Sidedness in Patients with Metastatic Colorectal Cancer Treated with Triplet First-line Chemotherapy.

BACKGROUND: Recent data have shown that right-sided colon cancer carries poorer prognosis compared to left-sided tumors. This study was aimed to evaluate the progression-free survival, overall survival of patients with metastatic colon cancer of right-sided versus left-sided primaries treated with triplet chemotherapy regimen. METHODS: The medical records of patients with metastatic colorectal cancer treated on phase I-II trial of combination Irinotecan, oxaliplatin, capecitabine, and bevacizumab were reviewed for sidedness of the primary. The analysis was performed for progression-free survival and overall survival according to the sidedness and other known prognostic factors. RESULTS: Out of 53 patients treated with triplet therapy, 11 had right sided and 42 had left-sided primaries. The median age for right-sided primaries was 46 (range 24-55) compared to 53 (range 32-74) in left-sided primaries. Median progression-free survival was 14 months for right vs 18 months for left sided tumors (Hazard ratio 0.72, 95% confidence interval 0.27-1.88, p=0.492) and median overall survival was 21 months for right vs 29 months for left sided tumors (Hazard ratio was 0.86, 95% CI 0.32-2.26, p=0.752). CONCLUSION: First-line triplet chemotherapy may overcome the difference in prognosis between right sided and left sided primaries in metastatic colorectal cancer. A larger analysis is warranted.

Tribulus terrestris versus placebo in the treatment of erectile dysfunction and lower urinary tract symptoms in patients with late-onset hypogonadism: A placebo-controlled study.

Aging is associated with a series of morphological and functional modifications that leads to reduced physiological efficiency and atrophy of various organs and systems. Tribulus terrestris induces its effect in fertility and sexual functions through the steroidal saponins, particularly the dominant saponins protodioscin. We aimed in this study to evaluate the efficacy and safety profiles of Tribulus terrestris in aging males with partial androgen deficiency who suffered from erectile dysfunction and lower urinary tract symptoms. A total of 70 randomized aging patients with erectile dysfunction and lower urinary tract symptoms were recruited from June 2017 to March 2018 from our andrology outpatient clinic. Thirty-five patients (group A) received Tribulus terrestris three times daily for 3 months and the other 35 patients (group B) received placebo. The mean of aspartate transaminase was elevated in group A after 3 months of receiving Tribulus terrestris (26.5 (before), 27.8 (after), respectively, p = 0.03). Moreover, there were significant elevations in the means of both total testosterone together with the score of the validated Arabic index of erectile function (5-item version of the International Index of Erectile Function) (2.2, 10.7 (before), 2.7, 16.1 (after), p < 0.001, p < 0.001, respectively). Finally, the mean of the total prostate-specific antigen was elevated in this group (1.4 (before), 1.7 (before), p = 0.007, respectively). Interestingly, there were no worsening of the lower urinary tract symptoms in group A as there was no change in the mean score of the international prostate symptom score, which was used to assess these symptoms before and after treatment (mean 14.4 (before), 14.6 (after), p = 0.67, respectively). In sum, this study replicates the findings of previous reports about the robust effect of this herbal medicine in elevating the testosterone level and improving the sexual function of patients who suffered from erectile dysfunction with partial androgen deficiency.

Androgen profiles among Egyptian adults considering liver status.

BACKGROUND AND AIM: Hepatitis C virus (HCV) and environmental hepatotoxins may have an indirect influence on health by altering the synthesis and function of hormones, particularly reproductive hormones. We aimed to evaluate liver diseases and sex steroid hormones in Egypt, which has the highest prevalence of HCV worldwide. METHODS: We measured markers of hepatitis B virus (HBV), HCV and schistosomiasis infection as well as liver function in 159 apparently healthy subjects. We measured total testosterone (T), sex-hormone binding globulin (SHBG) and albumin, and calculated the free androgen index. RESULTS: Anti-HCV antibodies were detected in 51% of men and 42% of women. Based on HCV reverse transcription PCR (RT-PCR) of 44 men and 33 women, 11% of men and 21% of women showed HCV viremia. There was schistosomiasis in 25% of men and 9% of women, and mixed HCV viremia and schistosomiasis in 57% of men and 52% of women. Compared with men with schistosomiasis only (mean 593.3 +/- 73.4 ng/dL), T was higher in men with mixed HCV viremia and schistosomiasis (mean 854.5 +/- 47.9 ng/dL; P = 0.006) and men with mixed chronic HCV and schistosomiasis (mean 812.1 +/- 43.3 ng/dL; P = 0.001). Men with mixed chronic HCV and schistosomiasis had also significantly higher SHBG (mean 57.7 +/- 3.9 ng/dL) than males with schistosomiasis only (mean 34.8 +/- SE 4.5 ng/dL; P = 0.0003). CONCLUSION: Future investigations should consider that a high prevalence of asymptomatic liver disease may alter associations between hormone concentrations and chronic disease etiology.

Early vaccination protects against childhood leukemia: A systematic review and meta-analysis.

Leukemia is the most commonly diagnosed childhood cancer, although its etiology is still largely unknown. Growing evidence supports a role for infection in the etiology of acute lymphocytic leukemia (ALL), and the involvement of the immune system suggests that vaccination may also play a role. However, the findings presented in the published literature are inconsistent. Therefore, we conducted a PRISMA systematic review and meta-analysis. 14 studies were identified and meta-analyzed. Vaccinations studied comprised Bacillus Calmette-Guérin (BCG) vaccine, Triple vaccine, Hepatitis B vaccine (HBV), Polio, Measles, Rubella, Mumps, trivalent MMR vaccine and Haemophilus influenza type B (HiB) vaccine. We observed a protective association between any vaccination in the first year of life and risk of childhood leukemia (summary odds ratio (OR) 0.58 [95% confidence interval (CI) 0.36-0.91]). When individual vaccines were analysed, some evidence of an association was seen only for BCG (summary OR 0.73 [95% CI 0.50-1.08]). In conclusion, early vaccination appears to be associated with a reduced risk of childhood leukemia. This finding may be underpinned by the association observed for BCG. Given the relatively imprecise nature of the results of this meta-analysis, our findings should be interpreted cautiously and replicated in future studies.