A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

The role of mesenchymal stem cells in the treatment and pathogenesis of psoriasis.

Psoriasis, a prevalent inflammatory skin condition impacting millions globally, continues to pose treatment challenges, despite the availability of multiple therapies. This underscores the demand for innovative treatments. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their capacity to modulate the immune system and facilitate tissue healing. Recent research indicates that MSCs don't just work through direct cell-to-cell interactions but also release extracellular vesicles (EVs), containing various bioactive substances like proteins, lipids, and nucleic acids. This article explores our current knowledge of psoriasis's origins and the potential utilization of MSCs and their EVs, particularly exosomes, in managing the condition. Additionally, we delve into how MSCs and EVs function in therapy, including their roles in regulating immune responses and promoting tissue repair. Lastly, we discuss the obstacles and opportunities associated with translating MSC-based treatments for psoriasis into clinical practice.

When less is more: The association between the expression of polymorphic CYPs and AFB1-induced HCC.

BACKGROUND: An individual's genetic fingerprint is emerging as a pivotal predictor of numerous disease- and treatment-related factors. Single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes play key roles in an individual's exposure to a malignancy-associated risk, such as Aflatoxin B1 (AFB1)-induced hepatocellular carcinoma (HCC). AIM: This study aimed at reviewing literature on the polymorphisms that exist in CYP enzymes and their possible link with susceptibility to AFB1-induced HCC. MATERIALS & METHODS: A set of keywords associated with the study subject of interest was used to search the Google Scholar and the PubMed database. The last ten years' worth of research projects were included in the results filter. The research involved HCC patients and any connection between polymorphic forms of CYP enzymes and their susceptibility to AFB1-induced HCC, including older but significant data. RESULTS: Variations in CYP1A2 and CYP3A4 were reported to impact the rate and magnitude of AFB1 bio-activation, thus influencing an individual's vulnerability to develop HCC. In HCC patients, the activity of CYP isoforms varies, where increased activity has been reported with CYP2C9, CYP2D6, and CYP2E1, while CYP1A2, CYP2C8, and CYP2C19 exhibit decreased activity. CYP2D6*10 frequency has been discovered to differ considerably in HCC patients. Rs2740574 (an upstream polymorphism in CYP3A4 as detected in CYP3A4*1B) and rs776746 (which affects CYP3A5 RNA splicing), both of which influence CYP3A expression, thus impacting the variability of AFB1-epoxide adducts in HCC patients. DISCUSSION: CYP1A2 is the primary enzyme accountable for the formation of harmful AFBO globally. CYP3A4, CYP3A5, CYP3A7, CYP2B7, and CYP3A3 are also implicated in the bio-activation of AFB1 to mutagenic metabolites. It is thought that CYP3A4 is the protein that interacts with AFB1 metabolism the most. CONCLUSION: Polymorphic variants of CYP enzymes have a functional impact on the susceptibility to AFB1-induced HCC. Outlining such variation and their implications may provide deeper insights into approaching HCC in a more personalized manner for guiding future risk-assessment, diagnosis, and treatment.

Life support for transitory exhausted CTLs.

Di Pilato et al. demonstrate that CXCR6 positions TCF-1- transitory CD8+ cytotoxic lymphocytes (CTLs) with perivascular CCR7+ dendritic cells (DCs) within the tumor stroma to receive IL-15 survival signals. The requirement for CXCR6 and its strong prediction of overall patient survival highlight the importance of continued CTL-DC interactions in sustaining tumor immunity.

Dual role of mesenchymal stem/stromal cells and their cell-free extracellular vesicles in colorectal cancer.

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.

New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies.

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.

An in vivo appraisal of Punica granatum peel extract's ultrastructural effect on cystic echinococcosis in mice.

In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.

Biochemical study of the effect of mesenchymal stem cells-derived exosome versus L-Dopa in experimentally induced Parkinson's disease in rats.

Parkinson's disease (PD) is a chronic and ongoing neurological condition. Unfortunately, as the dopaminergic terminals continue to deteriorate, the effectiveness of anti-Parkinson therapy decreases. This study aimed to examine the effects of BM-MSCs-derived exosomes in rats induced with Parkinson's disease. The goal was to determine their potential for neurogenic repair and functional restoration. Forty male albino rats were divided into four groups: control (group I), PD (group II), PD-L-Dopa (group III), and PD-exosome (group IV). Motor tests, histopathological examinations, and immunohistochemistry for tyrosine hydroxylase were performed on brain tissue. The levels of α-synuclein, DJ-1, PARKIN, circRNA.2837, and microRNA-34b were measured in brain homogenates. Rotenone induced motor deficits and neuronal alterations. Groups (III) and (IV) showed improvement in motor function, histopathology, α-synuclein, PARKIN, and DJ-1 compared to group (II). Group (IV) showed improvement in microRNA-34b and circRNA.2837 compared to groups (III) and (II). MSC-derived exosomes showed a greater suppression of neurodegenerative disease (ND) compared to L-Dopa in Parkinson's patients.

Trends in prescribing and outcomes in obese versus non-obese patients receiving rivaroxaban therapy: an observational study using real-world data.

PURPOSE: To investigate real-world prescribing trends and clinical outcomes based on body mass index (BMI) categorization in patients who received rivaroxaban therapy. METHODS: This was a retrospective cohort study involving all patients who received rivaroxaban therapy across all Hamad Medical Corporation (HMC) hospitals from 2015 to 2020. RESULTS: The number of patients initiated on rivaroxaban therapy significantly increased from 152 (3.3%) in 2015 to 1342 (28.9%) in 2020 (p <0.001). Within BMI categories, a similar increasing trend was observed in underweight, normal, and overweight patients, while from 2018 to 2020, there was a decreasing trend in rivaroxaban prescribing in all obese classes. The prevalence rate of all-cause mortality differed significantly between the BMI groups, with the highest mortality being among morbidly obese patients (BMI ≥ 40 kg/m2) (p< 0.001). On the other hand, no significant differences were found between the BMI groups in terms of bleeding, pulmonary embolism, deep vein thrombosis and stroke incidences. Multivariate logistic regression analyses showed that the likelihood of all-cause mortality was significantly higher in overweight and all categories of obese patients compared to underweight patients: overweight (OR: 5.3, 95% CI: 2.3-11.9, p< 0.001); obese class 1 (OR: 5.4, 95% CI: 2.3 - 12.2, p< 0.001); obese class 2 (OR: 6.5, 95% CI: 2.7 - 15.6, p< 0.001); and obese class 3 (OR: 3.7, 95% CI: 1.6 - 8.7, p = 0.003). CONCLUSIONS: Rivaroxaban prescribing has significantly increased over the years across general population, with a noticeable decline in obese population during the last few years (from 2018 onwards). Furthermore, an appreciable association was evident between all-cause mortality and BMI of these patients.

Assessment of macular microvascular changes in children following treatment of anisometropic myopic amblyopia using optical coherence tomography angiography.

PURPOSE: To evaluate macular microvascular changes in the form of foveal avascular zone (FAZ) area and vessel density in the superficial, deep capillary plexuses, and choriocapillaris using optical coherence tomography angiography (OCTA) in children with anisometropic myopic amblyopia before and after treatment. METHODS: This prospective observational study included 32 patients younger than 12 years old with anisomyopic amblyopia. OCTA was done before patients' treatment with optical correction with or without patching and was repeated after successful amblyopia treatment. Outcomes included superficial, deep, and choriocapillaris vessel density (VD) and superficial and deep FAZ areas. RESULTS: The study included 13 males (40.6%) and 19 females (59.4%), and the mean age was 9.52 ± 1.33 years. Fifty-three percent (53%) of patients needed only optical correction, and the remaining 47% needed additional patching therapy. After successful treatment, there was a significant improvement in amblyopic eyes in best-corrected visual acuity (p < 0.001), with higher VD values in superficial capillary plexuses (p < 0.001), deep capillary plexuses (p < 0.001), and foveal choriocapillaris (p = 0.030). In the glasses with patching subgroup, the difference between pre-treatment and post-treatment parameters revealed a significant improvement in vessel density in superficial retinal plexuses (foveal and parafoveal; p values 0.023 and < 0.001, respectively) and deep retinal plexuses (whole image, foveal, and parafoveal; p values 0.003, < 0.001, and 0.002, respectively). While amblyopic eyes treated with glasses alone had a significantly greater difference in choriocapillaris foveal VD (p value = 0.022). CONCLUSION: After effective amblyopia treatment, amblyopic eyes exhibited improved best-corrected visual acuity and better macular perfusion along the superficial, deep vascular density, and choriocapillaris foveal VD. CLINICAL TRIAL REGISTRATION: CinicalTrials.gov Identifier: NCT05223153.

The Efficacy of Bacteriocins Against Biofilm-Producing Bacteria Causing Bovine Clinical Mastitis in Dairy Farms: A New Strategy.

Using an alternative bio-product is one of the most promising ways to control bovine mastitis and avoid new intra-mammary infections. The aims of this study were to ascertain the prevalence of biofilm-forming bacteria responsible for causing clinical mastitis in dairy herds and to assess the effectiveness of bacteriocins, produced by Bacillus subtilis, in controlling the growth of these bacteria in the milk of animals. A total of 150 milk samples were collected from cows and buffalos suffering from mastitis and the etiological agents were isolated and identified by the VITEK-2-COMPACT-SYSTEM®. Additionally, the capability of the bacterial isolates to produce biofilms was determined. RT-PCR was used to detect enterotoxin-producing genes (sed and seb), resistance genes (mecA and blaZ), and biofilm-associated genes (icaA and fnbA) in the isolated bacteria. The susceptibility patterns of the bacterial isolates to bacteriocins were assessed using an agar well-diffusion assay. S. aureus was significantly more capable of producing biofilms than coagulase-negative Staphylococcus isolates. S. ubris was the strongest biofilm producer among the Streptococcus species. The sensitivity profiles of the Staphylococcus spp. (S. aureus and coagulase-negative Staphylococcus) and their biofilm producers to bacteriocins were significantly higher (100% and 90%, respectively) at the same concentration. Bacteriocins had a lethal effect on Staphylococci, Streptococci, and biofilm development at a dose of 250 µg/mL. In dairy farms, bacteriocins are a viable alternative treatment for the prevention and control of bovine clinical mastitis.

Clinical significance of immunohistochemical expression of DDR1 and ß-catenin in colorectal carcinoma.

BACKGROUND: Despite recent advances in therapy modalities of colorectal cancer (CRC), it is still the third cause of cancer-related deaths worldwide. Thus, the search for new target therapies became mandatory. DDR1 is a collagen receptor that has a suggested role in cellular proliferation, tumor invasion, and metastasis. MATERIAL AND METHODS: Forty-eight cases of CRC, 20 of CR adenoma, and 8 cases of non-tumoral colonic tissue were subjected to immunohistochemistry by DDR1 and ß-catenin antibodies. Results were compared among the different studied groups and correlated with clinicopathologic data and available survival data. Also, the expression of both proteins was compared versus each other. Results were compared among the 3 studied groups and correlated with clinicopathologic and survival data. RESULTS: It revealed a stepwise increase of DDR1 expression among studied groups toward carcinoma (P = 0.006). DDR1 expression showed a direct association with stage D in the modified Dukes' staging system (P = 0.013), higher-grade histologic types (P = 0.008), and lymph node invasion (P = 0.028) but inverse correlation with the presence of intratumoral inflammatory response (TIR) (P = 0.001). The shortest OS was associated with strong intensity of DDR1 (P = 0.012). The DDR1 and ß-catenin expressions were significantly correlated (P = 0.028), and the combined expression of both was correlated with TNM staging (P = 0.017). CONCLUSION: DDR1 overexpression is a frequent feature in CRC and CR adenoma. DDR1 is a poor prognostic factor and a suppressor of the TIR. DDR1 and ß-catenin seem to have a synergistic action.

Genetic Risk of Rheumatoid Arthritis: A Case Control Study.

Vitamin D effects are mediated by vitamin D receptors (VDRs), which are influenced by various genetic polymorphisms, including ApaI and BsmI. These polymorphisms have been linked to several diseases, including rheumatoid arthritis (RA). This study aimed to compare the frequency and association of VDR ApaI and BsmI gene polymorphisms, serum 25-hydroxy vitamin D (25-(OH)-D) levels, and calcium (Ca) levels between a RA group and a matched healthy control group. In one hundred RA patients and fifty healthy controls, the genotypes of the VDR ApaI and BsmI gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP). Both Serum 25-(OH)-D level and calcium level were measured in the two groups. There was no significant difference between the cases and controls regarding the VDR ApaI gene polymorphism (p = 0.89). A significant difference was observed between the cases and controls in terms of the VDR BsmI gene polymorphism (p = < 0.001). The serum levels of 25-(OH)-D and calcium were significantly lower in the RA group compared to the control group (p = 0.04 and < 0.001 respectively). Significantly higher serum vitamin D levels were associated with the aa genotype (p = 0.007). Significantly increased calcium levels were associated with the AA genotype (p = 0.02). No significant difference was found among BsmI polymorphisms regarding vitamin D and Ca levels (p = 0.25 and 0.87 respectively). Vitamin D receptor gene BsmI polymorphism but not ApaI polymorphism could be a marker of RA susceptibility. Vitamin D and Ca levels are negatively affected by RA. Vitamin D receptor gene ApaI polymorphism contributes to vitamin D and Ca levels.

Retrospective review of medication allergy labeling among patients admitted to a tertiary hospital in Qatar.

Background: Timely access to accurate, up-todate drug allergy information is critical to avoid potentially life-threatening adverse drug reactions (ADRs). However, the completeness and accuracy of allergy documentation remain a challenge. Inappropriate allergy documentation usually necessitates alternative treatments, increases costs, and may negatively impact patients' outcomes. Objectives: Review medication allergy labeling documentation, identify the most reported medication class, and describe allergic reactions based on the reported severity. Methods: A retrospective cross-sectional audit including all medication allergy labeling documentation for patients admitted to Hamad General Hospital (HGH) from January-December 2022 was conducted. A list of patients with medication allergies was generated from the pharmacy system, which included patients' demographics, medication names, documented allergy severity, and any other comments. The list was reviewed, and medications were categorized into different classes. Results: 2856 allergy documentation for 2431 unique patients were identified and included in the analyses. The mean age of included patients was 43 years old, with 73.2% (1780) being females. Among the reported allergic reactions, 11.8% (336) were documented as severe allergic reactions, 51.1% (1457) were moderate, and 37.1% (1060) were mild. Antibiotics were the most common documented allergens, representing 42.1% of all reported allergies, followed by non-steroidal anti-inflammatory drugs (20.7%, n=591), and paracetamol (5.3%, n=151). Of all the reported allergies, only 6 (0.21%) cases had documented confirmatory allergy tests done. Further analysis of the reported allergies revealed that 1.2% (34) of the allergies had documentation to counteract the allergy labeling through either revised patient history or re-challenging. Despite such, allergy labeling was kept in the medical profile without proper de-labeling. Conclusion: Allergy labeling documentation is a key to safe medication prescribing. However, standardized allergy documentation should be implemented to include a brief description and onset of the symptoms. Additionally, a safe de-labeling pathway should be adopted. Most of the allergy documentation was based on patients' or family/parents' reports, while actual allergies observed by a healthcare provider were limited.

Autoxidation of 4-Hydrazinylquinolin-2(1H)-one; Synthesis of Pyridazino[4,3-c:5,6-c']diquinoline-6,7(5H,8H)-diones.

An efficient synthesis of a series of pyridazino[4,3-c:5,6-c']diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1H)-ones. IR, NMR (1H and 13C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure. The possible mechanism for the reaction is also discussed.

Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action.

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a−e and 7a−e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a−e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal−Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a−e and 7a−e were evaluated. Compounds 4a−e and 7a−e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids.

Titrated oral misoprostol versus static regimen of oral misoprostol for induction of labour: a systematic review and meta-analysis.

We aimed to conduct a systematic review and meta-analysis to compare the efficacy and safety of titrated oral misoprostol versus static oral misoprostol for labour induction. We searched for the available randomised clinical trials (RCTs) in the Cochrane Library, PubMed, ISI web of science, Scopus, and ClinicalTrials.gov. We included RCTs compared titrated oral misoprostol versus static regimen of oral misoprostol during labour induction. Our main outcomes were vaginal and caesarean delivery rates, uterine tachysystole, misoprostol side effects, and neonatal adverse events. Three RCTs met our inclusion criteria with a total number of 360 patients. The vaginal delivery rate did not significantly differ between both groups (p = 0.49). Titrated oral misoprostol was associated with significant increase in the caesarean delivery rate compared to static oral misoprostol (p = 0.04). Moreover, titrated oral misoprostol led to significant increase in the uterine tachysystole and misoprostol side effects (p = 0.01 & p = 0.003, respectively). There were no differences among both groups regarding different neonatal adverse events. In conclusion, titrated oral misoprostol increases the incidence of caesarean delivery, uterine tachysystole, and misoprostol side effects with a similar vaginal delivery rate compared to static dose misoprostol. Thus, static oral misoprostol should be used instead of titrated oral misoprostol during labour induction. Impact StatementWhat is already known on this subject? Different studies have evaluated titrated oral misoprostol administration for induction of labour and proved their efficacy in comparison with other induction methods. However, there is controversy among the published studies between titrated oral misoprostol and static oral misoprostol during induction of labour. A recent study concluded that hourly titrated misoprostol and static oral misoprostol are equally safe and effective when utilised for induction of labour with no fear of any adverse events. However, another study recommended static oral misoprostol administration for labour induction as it was linked to a lower caesarean section incidence, fewer drug side effects, and decline in complication rates in comparison with titrated oral misoprostol.What the results of this study add? Titrated oral misoprostol increases the incidence of caesarean delivery, uterine tachysystole, and misoprostol side effects with a similar vaginal delivery rate compared to static dose misoprostol.What the implications are of these findings for clinical practice and/or further research? Static oral misoprostol should be used instead of titrated oral misoprostol during labour induction. More future trials are required to confirm our findings.

Evaluation of the anterior chamber angle by anterior segment optical coherence tomography after implantable phakic contact lens implantation in myopic eyes.

PURPOSE: To evaluate the changes in the angle of the AC and lens vault after IPCL implantation by AS-OCT in myopic patients. METHODS: This was a prospective observational study involving 30 myopic eyes implanted with IPCL. AS-OCT was used to evaluate lens vault and AC angle parameters including anterior chamber angle, angle opening distance and trabecular-iris space area (TISA) at 1, 3 and 6 months postoperatively. RESULTS: All 3 AC angle parameters were significantly reduced at the 1st postoperative month compared to preoperative values, but remained stable thereafter with no significant change at the 3rd or 6th postoperative months. The lens vault showed no significant change over the entire follow-up period. CONCLUSION: IPCL implantation is a safe method for correction of myopia with stable AC angle narrowing over the course of 6 months postoperatively as monitored using AS-OCT.

Prognostic values of myeloid differentiation factor 88 (MYD88) and transducin (ß)-like receptor 1 (TBLR1) expression in tissues of diffuse large B-cell non-Hodgkin lymphoma patients - an immunohistochemical study.

Introduction: Diffuse large B-cell non- Hodgkin lymphoma (DLBCL) is the largest common category of adult lymphoma. Recurrence and treatment resistance occurs in one-third of cases, triggering them to the progressive stage of DLBCL after treatment. Detection of novel predictive and prognostic biomarkers leads to improvement of its treatment and prognosis. Aim of the study: To assess the prognostic roles of protein expression of myeloid differentiation factor 88 (MYD88) and transducin (ß)-like receptor 1 (TBLR1) in tissues of DLBCL patients. Material and methods: In the current study we included tissues from 100 cases of DLBCL. For immunohistochemistry, tissues were stained with MYD88 and TBLR1. We followed patients for about 3 years, and then we correlated their expression with clinicopathological and prognostic parameters. Results: Higher MYD88 and TBLR1 expressions were associated with presence of B symptoms, fever, night sweat, advanced stage, bone marrow involvement and bulky nodal size, presence of extra-nodal extension, unfavourable relapse-free survival, and unfavourable overall survival rates (p < 0.001). Conclusions: overexpression of MYD88 and TBLR1 expression was present in DLBCL patients and was associated with unfavourable clinicopathological and prognostic parameters.

Labeling of penicillin allergy in patients admitted to a tertiary hospital in Qatar: A retrospective audit.

BACKGROUND: Penicillin (PNC) allergy is a major healthcare concern that necessitates antibiotic substitution which is associated with increased costs, worse clinical outcomes, and increased risks of antimicrobial resistance. Many patients are labeled as PNC allergic; however, this has been rarely confirmed. In this audit, we aimed to determine the characteristics of PNC allergy labeling. METHODS: A list of all the patients labeled with PNC allergy who presented to the Hamad General Hospital (HGH) for any medical reason from January to December 2021 was generated from pharmacy system. Of those, 30% were randomly selected for audit review. Electronic health records of the selected patients were retrospectively reviewed to identify the allergy labeling characteristics and whether the patients had recently received an antibiotic within the PNC class without developing any allergic reaction. RESULTS: Of the 464 patients identified with labelled PNC allergy, 139 patients were randomly selected and reviewed. Of the reviewed patients, 82 (59%) were women with an average ( ± SD) age of 46 ( ± 16.5) years. Forty-six patients were categorized to have a mild PNC allergy, and only 18 were categorized as severe with the remaining patients categorized as having a moderate PNC allergy. Despite documentation of severity, an accurate description of the allergic reaction event was significantly lacking with only 30/139 (21.5%) patients having clear documentation of the event description. Twenty (14.4%) patients labeled as PNC allergic received at least one antibiotic within the PNC class (e.g., piperacillin-tazobactam, ampicillin-sulbactam, or amoxicillin-clavulanic acid) safely without any documented reactions. Interestingly, of those 20 patients, 4 were categorized as being severely allergic to PNC. However, as more than 80 patients presented to the hospital for reasons not requiring antibiotics; experiences with PNC could not be assessed effectively. CONCLUSION: Poor documentation of the details of allergic reactions may falsely affect future antibiotic decisions. The results of this audit highlight the need for standardizing the documentation process of medication allergy. In addition, reviewing the patient's experience with other drugs within the PNC class can guide healthcare providers during the PNC allergy evaluation.