Atypical Presentation of Idiopathic Intracranial Hypertension: A Case Series and Literature Review.

Idiopathic intracranial hypertension (IIH) is a condition in which intracranial pressure (ICP) increases without an apparent cause. Typically, patients present with headaches, dizziness, pulsatile tinnitus, visual disturbances, blurred vision, diplopia, photophobia, visual field defects, and papilledema on fundoscopy. The association between IIH, spontaneous cerebrospinal fluid (CSF) rhinorrhea, and arachnoid cysts has been discussed in the literature; however, there is no clear explanation for this association. We aimed to present a series of four patients with a confirmed diagnosis of IIH with atypical presentations, discuss the management of each case, and provide an explanation for this association to alert clinicians to the atypical presentation of IIH and facilitate early diagnosis and proper treatment of this condition by CSF diversion. This was a retrospective case series of all patients who were diagnosed with IIH and showed improvement after ventriculoperitoneal shunt insertion after failure of at least one operative intervention resulting from primary radiological and clinical findings in 2001 to 2022. Data on demographics, clinical presentation, radiological findings, surgical management, and diagnostic criteria for IIH were recorded. We identified four patients with a confirmed diagnosis of IIH who presented with atypical presentations as follows: intracranial arachnoid cyst, cervical spine arachnoid cyst, giant Virchow perivascular space, and spontaneous CSF (CSF) rhinorrhea. All patients responded to CSF diversion after failure of surgical treatment targeting the primary pathology. IIH should be suspected after the failure of primary surgical treatment in cases of spontaneous CSF rhinorrhea, spinal and cranial arachnoid cysts, and symptomatic ventriculoperitoneal shunt. Treatment in such situations should be directed toward IIH with CSF diversion.

Correction: Habit Strength, Medication Adherence, and Habit-Based Mobile Health Interventions Across Chronic Medical Conditions: Systematic Review.

[This corrects the article DOI: 10.2196/17883.].

Stereotactic body radiation therapy for prostate cancer: a dosimetric comparison of IMRT and VMAT using flattening filter and flattening filter-free beams.

This retrospective study was performed to evaluate plan quality and treatment delivery parameters of stereotactic body radiation therapy (SBRT) for prostate cancer. The study utilized different isocentric modulated techniques: intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using 6 MV flattening filter (FF) and 10 MV flattening filter-free beams (FFF). Fifteen retrospective prostate cancer patients were selected for this study. Sixty plans were created with an SBRT-prescribed dose of 36.25 Gy delivered in five fractions. Planning target volume (PTV) coverage, plan quality indices, doses delivered to organs at risk (OARs), and treatment delivery parameters were compared for all plans. It turned out that VMAT plans, particularly those using the FFF beam, provided superior target conformality and a steeper dose gradient as compared to IMRT plans. Additionally, VMAT plans showed better OARs sparing compared to IMRT plans. However, IMRT plans delivered a lower maximum dose to the target than VMAT plans. Importantly, the VMAT plans resulted in reduced treatment delivery parameters, including beam on time (BOT), monitor unit (MU), and modulation factor (MF), compared to IMRT plans. Furthermore, a statistically significant difference was observed in BOT and mean body dose between FF and FFF beams, with FFF beams showing superior performance. Considering all results, VMAT using 10 MV (FFF) is suggested for treating prostate cancer patients with SBRT. This offers the fastest delivery in addition to maintaining the highest plan quality.

Comparative metabolomics study on the secondary metabolites of the red alga, Corallina officinalis and its associated endosymbiotic fungi.

Marine endosymbionts have gained remarkable interest in the last three decades in terms of natural products (NPs) isolated thereof, emphasizing the chemical correlations with those isolated from the host marine organism. The current study aimed to conduct comparative metabolic profiling of the marine red algae Corallina officinalis, and three fungal endosymbionts isolated from its inner tissues namely, Aspergillus nidulans, A. flavipes and A. flavus. The ethyl acetate (EtOAc) extracts of the host organism as well as the isolated endosymbionts were analyzed using ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-MS/MS)in both positive and negative ion modes, applying both full scan (FS) and all ion fragmentation (AIF) modes. Extensive interpretation of the LC-MS/MS spectra had led to the identification of 76 metabolites belonging to different phytochemical classes including alkaloids, polyketides, sesquiterpenes, butyrolactones, peptides, fatty acids, isocoumarins, quinones, among others. Metabolites were tentatively identified by comparing the accurate mass and fragmentation pattern with metabolites previously reported in the literature, as well as bioinformatics analysis using GNPS. A relationship between the host C. officinalis and its endophytes (A. flavus, A. nidulans, and A. flavipes) was discovered. C. officinalis shares common metabolites with at least one of the three endosymbiotic fungi. Some metabolites have been identified in endophytes and do not exist in their host. Multivariate analysis (MVA) revealed discrimination of A. flavipes from Corallina officinalis and other associated endophytic Aspergillus fungi (A. flavus and A. nidulans).

Onion Skin Is Not a Universal Firing Pattern for Spinal Motoneurons: Simulation Study.

Muscle force is modulated by sequential recruitment and firing rates of motor units (MUs). However, discrepancies exist in the literature regarding the relationship between MU firing rates and their recruitment, presenting two contrasting firing-recruitment schemes. The first firing scheme, known as "onion skin", exhibits low-threshold MUs firing faster than high-threshold MUs, forming separate layers akin to an onion. This contradicts the other firing scheme, known as "reverse onion skin" or "after-hyperpolarization (AHP)", with low-threshold MUs firing slower than high-threshold MUs. To study this apparent dichotomy, we employed a high-fidelity computational model that prioritizes physiological fidelity and heterogeneity, allowing versatility in the recruitment of different motoneuron types. Our simulations indicate that these two schemes are not mutually exclusive but rather coexist. The likelihood of observing each scheme depends on factors such as the motoneuron pool activation level, synaptic input activation rates, and MU type. The "onion skin" scheme does not universally govern the encoding rates of MUs but tends to emerge in unsaturated motoneurons (cells firing < their fusion frequency that generates peak force), whereas the "AHP" scheme prevails in saturated MUs (cells firing at their fusion frequency), which is highly probable for S-type MUs. When unsaturated, FF-type MUs always show the "onion skin" scheme, while S-type MUs do not show either one. FR-type MUs are generally similar but show weaker "onion skin" behaviors than FF-type MUs. Our results offer an explanation for the longstanding dichotomy regarding MU firing patterns, shedding light on the factors influencing the firing-recruitment schemes.

A new label free spiral sensor using impedance spectroscopy to characterize hepatocellular carcinoma in tissue and serum samples.

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer, predominantly affecting patients with chronic liver diseases such as hepatitis B or C-induced cirrhosis. Diagnosis typically involves blood tests (assessing liver functions and HCC biomarkers), imaging procedures such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), and liver biopsies requiring the removal of liver tissue for laboratory analysis. However, these diagnostic methods either entail lengthy lab processes, require expensive imaging equipment, or involve invasive techniques like liver biopsies. Hence, there exists a crucial need for rapid, cost-effective, and noninvasive techniques to characterize HCC, whether in serum or tissue samples. In this study, we developed a spiral sensor implemented on a printed circuit board (PCB) technology that utilizes impedance spectroscopy and applied it to 24 tissues and sera samples as proof of concept. This newly devised circuit has successfully characterized HCC and normal tissue and serum samples. Utilizing the distinct dielectric properties between HCC cells and serum samples versus the normal samples across a specific frequency range, the differentiation between normal and HCC samples is achieved. Moreover, the sensor effectively characterizes two HCC grades and distinguishes cirrhotic/non-cirrhotic samples from tissue specimens. In addition, the sensor distinguishes cirrhotic/non-cirrhotic samples from serum specimens. This pioneering study introduces Electrical Impedance Spectroscopy (EIS) spiral sensor for diagnosing HCC and liver cirrhosis in clinical serum-an innovative, low-cost, rapid (< 2 min), and precise PCB-based technology without elaborate sample preparation, offering a novel non-labeled screening approach for disease staging and liver conditions.

Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1-G93A mice.

Persistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)-G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS. To fill this gap, we measured the net and individual PIC and POC components of wild-type (WT) and SOD MNs in current clamp and voltage clamp during disease progression (assessed by neuroscores). We show that SOD MNs of symptomatic mice experience a much larger net PIC, relative to WT cells from age-matched littermates. Specifically, the Na+ and Ca2+ PICs are larger, whereas the lasting SK-mediated (SKL) POC is smaller than WT (Na+ PIC is the largest and SKL POC is the smallest components in SOD MNs). We also show that PIC dysregulation is present at symptom onset, is sustained throughout advanced disease stages and is proportional to SOD MN cell size (largest dysregulation is in the largest SOD cells, the most vulnerable in ALS). Additionally, we show that studying disease progression using neuroscores is more accurate than using SOD mouse age, which could lead to misleading statistics and age-based trends. Collectively, this study contributes novel PIC and POC data, reveals ionic mechanisms contributing to the vulnerability differential among MN types/sizes, and provides insights on the roles PIC and POC mechanisms play in MN excitability dysfunction in ALS. KEY POINTS: Individual persistent inward currents (PICs) and persistent outward currents (POCs) have never been examined before in spinal motoneurons (MNs) of symptomatic amyotrophic lateral sclerosis (ALS) mice. Thus, we contribute novel PIC and POC data to the ALS literature. Male SOD MNs of symptomatic mice have elevated net PIC, with larger Na+ and Ca2+ PICs but reduced SKL POC vs. wild-type littermates. Na+ PIC is the largest and SKL POC is the smallest current in SOD cells. The PIC/POC dysregulation is present at symptom onset. PIC dysregulation is sustained throughout advanced disease, and is proportional to SOD MN size (largest dysregulation is in the largest cells, the most vulnerable in ALS). Thus, we reveal ionic mechanisms contributing to the vulnerability differential among MN types/sizes in ALS. Studying disease progression using SOD mice neuroscores is more accurate than using age, which could distort the statistical differences between SOD and WT PIC/POC data and the trends during disease progression.

Donor Types and Outcomes of Transplantation in Myelofibrosis: A CIBMTR Study.

We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

Low concentrations of soybean lecithin nanoparticles had a positive impact on Holstein bulls' cryopreserved semen.

Spermatozoa can experience negative changes when subjected to freezing and thawing, including lowered motility, viability and acrosome response. Herein, the effects of different concentrations of soybean lecithin nanoparticles on cryopreserved Holstein bull semen were examined. Semen was collected, cryopreserved and utilized for sperm kinetic parameter analysis following dilution, equilibration and thawing with 0.5% soybean lecithin (E1), the control extender, and 0.75% (E2), 0.5% (E3), 0.25% (E4) and 0.125% (E5) of lecithin nanoparticles. Results revealed that following dilution, the progressive motility (PM) at E3, E4 and E5 of lecithin nanoparticles was higher (p < .05) than it was for E2. After equilibration, compared to the E1, E2, and E3 values, the PM, vitality, normal morphology, membrane integrity and intact acrosome values at the E5 were consistently greater (p < .05). Comparing the percentages of intact acrosome and membrane integrity at E2 and E3 to E4 and E5, a substantial decrease (p < .05) was seen. Following thawing, the percentage of PM improved at E2 and E5, even though their mean PM values were similar (p > .05) compared to E1, E3 and E4. Vigour and progression parameters of sperm (DAP, DCL, DSL, VAP, VCL, VSL and STR) at E5 were higher (p < .05) than those at E1, E2, E3 and E4. In conclusion, the cryopreserved sperm from Holstein bulls revealed outstanding properties both after equilibration and after thawing with 0.125% lecithin nanoparticles, and they were sensitive to high dosages.

The palatopharyngeal muscle in otolaryngology practice: an anatomical-based surgical report.

OBJECTIVES: The author discusses current otolaryngological procedures employing the palatopharyngeus muscle, based on the surgical anatomy of the muscle and its neural supply. These techniques should be deeply revised for more conservative, anatomically-based maneuvers. METHODS: Revision of anatomical and surgical research and comments with the provision of a primary concept. RESULTS: The palatopharyngeus muscle is innervated by the pharyngeal plexus (the vagus and the accessory nerves) with additional fibers from the lesser palatine nerves. The innervation enters the muscle mainly through its lateral border. CONCLUSIONS: The palatopharyngeus muscle has a fundamental role in swallowing and speech. The muscle helps other dilators to maintain upper airway patency. Sphincter pharyngoplasty should be revised as regards its role as a sphincter. Palatopharyngeal procedures for OSA employing the palatopharyngeus muscle should follow the conservative, anatomically-based, and non-neural ablation concept.

Formulation of Saxagliptin Oral Films: Optimization, Physicochemical Characterization, In-Vivo Assessment, and In-Vitro Real-Time Release Monitoring via a Novel Polyaniline Nanoparticles-Based Solid-Contact Screen Printed Ion-Selective Electrode.

Oral dispersible films have received broad interest due to fast drug absorption and no first-path metabolism, leading to high bioavailability and better patient compliance. Saxagliptin (SXG) is an antidiabetic drug that undergoes first-path metabolism, resulting in a less active metabolite, so the development of SXG oral dispersible films (SXG-ODFs) improves SXG bioavailability. The formula optimisation included a response surface experimental design and the impact of three formulation factors, the type and concentration of polymer and plasticiser concentration on in-vitro disintegration time and folding endurance. Two optimised SXG-ODFs prepared using either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose were investigated. SXG-ODFs prepared with PVA demonstrated a superior rapid disintegration time, ranging from 17 to 890 s, with the fastest disintegration time recorded at 17 s. These short durations can be attributed to the hydrophilic nature of PVA, facilitating rapid hydration and disintegration upon contact with saliva. Additionally, PVA-based films displayed remarkable folding endurance, surpassing 200 folds without rupture, indicating flexibility and stability. The high tensile strength of PVA-based films further underscores their robust mechanical properties, with tensile strength values reaching up to 4.53 MPa. SXG exhibits a UV absorption wavelength of around 212 nm, posing challenges for traditional quantitative spectrophotometric analysis, so a polyaniline nanoparticles-based solid-contact screen-printed ion-selective electrode (SP-ISE) was employed for the determination of SXG release profile effectively in comparison to HPLC. SP-ISE showed a better real-time release profile of SXG-ODFs, and the optimised formula showed lower blood glucose levels than commercial tablets.

Use of Patient-Centered Technology and Digital Interventions in Pediatric and Adult Patients with Hematologic Malignancies.

PURPOSE OF REVIEW: As society continues to advance in technology, it is important to address how this advancement can impact and enhance patient care. The purpose of this review is to identify patient-centered technology currently available for adult and pediatric patients with and those having survived hematologic malignancies. Given that patients with hematologic malignancies often have to adhere to strenuous medication regimens, coordinate care with many different providers, manage symptoms associated with treatment, and manage late effects associated with survivorship, they would benefit greatly from patient-centered technology aimed at decreasing these burdens. RECENT FINDINGS: This review found various available digital interventions for this patient population and focuses on an overview of commercially available smartphone applications, patient portals, and technology for remote monitoring. In summary, many digital interventions exist for use in the medical care of oncology patients. The incorporation of these interventions can allow for more personalized medical care, better organization of treatment plans by caregivers at home, and easy delivery of accurate medical information.

Transcriptome Profiling of a Salt Excluder Hybrid Grapevine Rootstock 'Ruggeri' throughout Salinity.

Salinity is one of the substantial threats to plant productivity and could be escorted by other stresses such as heat and drought. It impairs critical biological processes, such as photosynthesis, energy, and water/nutrient acquisition, ultimately leading to cell death when stress intensity becomes uncured. Therefore, plants deploy several proper processes to overcome such hostile circumstances. Grapevine is one of the most important crops worldwide that is relatively salt-tolerant and preferentially cultivated in hot and semi-arid areas. One of the most applicable strategies for sustainable viticulture is using salt-tolerant rootstock such as Ruggeri (RUG). The rootstock showed efficient capacity of photosynthesis, ROS detoxification, and carbohydrate accumulation under salinity. The current study utilized the transcriptome profiling approach to identify the molecular events of RUG throughout a regime of salt stress followed by a recovery procedure. The data showed progressive changes in the transcriptome profiling throughout salinity, underpinning the involvement of a large number of genes in transcriptional reprogramming during stress. Our results established a considerable enrichment of the biological process GO-terms related to salinity adaptation, such as signaling, hormones, photosynthesis, carbohydrates, and ROS homeostasis. Among the battery of molecular/cellular responses launched upon salinity, ROS homeostasis plays the central role of salt adaptation.

Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data.

Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug-induced neutropenia (IDIN) that may put them at risk of infection. The purpose of this analysis was to examine the rates of severe IDIN and risk of serious infections at different ANC levels in patients treated with deferiprone. Events of severe IDIN (ANC <0.5×109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by 3 discrete ANC levels: Group 1, 0.2-0.5×109/L; Group 2, 0.1-0.199×109/L; Group 3, <0.1×109/L. In clinical trials, 22 events of severe IDIN were observed (Group 1, n=9; Group 2, n=3; Group 3, n=10); total deferiprone exposure was 1990.26 patient-years; and rates of severe IDIN per 100 patient-years were 0.45 in Group 1, 0.15 in Group 2, and 0.50 in Group 3. All serious infections were in Group 3 (3/10, 30.0%). In the postmarketing setting, 176 events of severe IDIN were reported (Group 1, n=65; Group 2, n=20; Group 3, n=91); total deferiprone exposure was 111,570.24 patient-years; and rates of severe IDIN per 100 patient-years were 0.06 in Group 1, 0.02 in Group 2, and 0.08 in Group 3. Rates of serious infection were 7.7% (n=5/65) in Group 1, 10% (n=2/20) in Group 2, and 13.2% (n=12/91) in Group 3. Our findings suggest that in patients receiving deferiprone, ANC below 0.2×109/L carries a high risk of serious infections, consistent with the recent neutropenia guidelines that agranulocytosis with ANC <0.2×109/L is associated with a high risk of serious infections.

The Association Between Components of Metabolic Syndrome and Abnormal Electrocardiograms in the Saudi Population: A Retrospective Study.

REVIEW: Saudi Arabia has a high metabolic syndrome (MetS) prevalence. Having MetS increases the risk of cardiovascular disease (CVD), CVD mortality, and myocardial infarction (MI). There is a lack of information regarding MetS and electrocardiogram (ECG) abnormalities in Saudi Arabian populations. Further, it is unclear to what extent MetS components are associated with abnormal ECGs in Saudi populations. AIM: We investigated whether ECG abnormalities and MetS are associated with Saudi adults. Furthermore, we assessed the relationship between ECG abnormalities and the components of MetS based on the age and gender of the individuals.  Materials and methods: A retrospective study was conducted at Dr Soliman Fakeeh Hospital in Jeddah, Saudi Arabia, on 208 patients with MetS. Participants' clinical and laboratory data were examined. A detailed analysis of the ECG was performed. ECG abnormalities were divided into minor and major abnormalities based on Novacode criteria. In addition to ischemic ECG findings, the ECG showed prolonged PR intervals, prolonged P duration, prolonged QRS duration, and prolonged QTc intervals.  Results: One hundred and thirty-seven participants (65.9%) had elevated fasting blood glucose (FBS), 129 had central obesity (62%), 93 had high blood pressure (BP) (44.7%), 74 had elevated triglycerides (35.6%), and 49 had low high-density lipoprotein (23.6%). An abnormal ECG was found in 86 (41.3%) participants. It consisted of ischemic ECGs, atrioventricular (AV) block (first and second degrees), bundle branch block (right bundle branch block [RBBB], left bundle branch block [LBBB], RBBB with left anterior hemiblock, RBBB with right anterior hemiblock), arrhythmias (premature ventricular contractions [PVCs], premature atrial complexes [PACs], atrial fibrillation [AF], sinus bradycardia, sinus arrhythmia), prolonged QTc, prolonged PR interval, and prolonged QRS duration. There were 29 (13.9%) cases with multiple ECG abnormalities, 57 (27.4%) had one abnormal ECG, 42 (20.2%) had minor abnormal ECGs, and 44 (21.2%) had major abnormal ECGs. Middle-aged and elderly males accounted for the majority of these ECG changes. In the central obesity group, 22 participants (10.6%) had ischemic ECGs, 18 (8.7%) had prolonged QTc, 10 (4.8%) had first-degree AV block, 6 (2.9%) had sinus bradycardia, 7 (3.4%) had RBBB, 4 (1.9%) had LBBB, 3 (1.4%) had PVCs, 2 (1%) had ventricular preexcitation, and one (0.5%) had PACs. An elevated FBS group included 19 participants (9.1%) with an ischemic ECG, 18 (8.7%) with a prolonged QTc, 11 (5.3%) with a first-degree AV block, 9 (4.3%) with sinus bradycardia, 6 (2.9%) with slight ST-T abnormality, 5 (2.4%) with RBBB, and 5 (2.4%) with LBBB. Finally, one (0.5%) of these patients had second-degree AV block, RBBB with left anterior hemiblock, left anterior hemiblock, PVCs, AF, ventricular preexcitation, and sinus arrhythmia for each. CONCLUSION: Saudi Arabian populations with MetS were strongly associated with abnormal ECG findings, particularly ischemic ECG findings, AV block (first and second degrees), and BBB (RBBB, LBBB). Middle-aged and elderly males accounted for the majority of these ECG changes. The most important factors contributing to ECG changes were elevated FBS and central obesity.

The Role of Direct Oral Anticoagulants in the Treatment of Cancer-Associated Venous Thromboembolism: Review by Middle East and North African Experts.

Venous thromboembolism is a leading cause of morbidity and mortality in patients with active cancer who require anticoagulation treatment. Choice of anticoagulant is based on careful balancing of the risks and benefits of available classes of treatment: vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Results from randomized controlled trials have shown the consistent efficacy of DOACs versus LMWH in the treatment of cancer-associated venous thromboembolism (VTE). However, increased major gastrointestinal bleeding was observed for edoxaban and rivaroxaban, but not apixaban, compared with LMWH dalteparin. Most guidelines recommend DOACs for the treatment of cancer-associated VTE in patients without gastrointestinal or genitourinary cancer, and with considerations for renal impairment and drug-drug interactions. These updates represent a major paradigm shift for clinicians in the Middle East and North Africa. The decision to prescribe a DOAC for a patient with cancer is not always straightforward, particularly in challenging subgroups of patients with an increased risk of bleeding. In patients with gastrointestinal malignancies who are at high risk of major gastrointestinal bleeds, apixaban may be the preferred DOAC; however, caution should be exercised if patients have upper or unresected lower gastrointestinal tumors. In patients with gastrointestinal malignancies and upper or unresected lower gastrointestinal tumors, LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable. In this review, we discuss the overall evidence for DOACs in the treatment of cancer-associated VTE and provide treatment suggestions for challenging subgroups of patients with cancer associated VTE.

Patients with cancer are at risk of blood clots forming in their veins, which can cause illness and death. To prevent such blood clots, most patients with cancer need anticoagulant therapy. There are three types of anticoagulants available for the treatment of cancer-associated blood clots in a vein, namely, vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Drug trials have shown that DOACs are more effective than LMWH; however, DOACs can have a greater risk of causing major gastrointestinal bleeding. Among DOACs, edoxaban and rivaroxaban are drugs associated with higher rates of gastrointestinal bleeding. Recently updated guidelines for doctors recommend that DOACs be used as the first treatment for patients with cancer at risk of blood clot formation in a vein. For doctors in the Middle East and North Africa, this new approach differs from existing practices. Notably, choosing a treatment also depends on the type of cancer, because gastrointestinal cancers and cancers of the genitals and urinary system have an especially high risk of gastrointestinal bleeding. The choice also depends on the presence of kidney problems, drug­drug interactions, and access to the drugs. Apixaban may be the preferred DOAC in patients with gastrointestinal cancer, but this drug should be used with care in patients with upper or unresected lower gastrointestinal tumors. For patients with upper or unresected lower gastrointestinal tumors, treatment with LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable.

Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities.

ABSTRACT: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Fosgonimeton attenuates amyloid-beta toxicity in preclinical models of Alzheimer's disease.

Positive modulation of hepatocyte growth factor (HGF) signaling may represent a promising therapeutic strategy for Alzheimer's disease (AD) based on its multimodal neurotrophic, neuroprotective, and anti-inflammatory effects addressing the complex pathophysiology of neurodegeneration. Fosgonimeton is a small-molecule positive modulator of the HGF system that has demonstrated neurotrophic and pro-cognitive effects in preclinical models of dementia. Herein, we evaluate the neuroprotective potential of fosgonimeton, or its active metabolite, fosgo-AM, in amyloid-beta (Aß)-driven preclinical models of AD, providing mechanistic insight into its mode of action. In primary rat cortical neurons challenged with Aß (Aß1-42), fosgo-AM treatment significantly improved neuronal survival, protected neurite networks, and reduced tau hyperphosphorylation. Interrogation of intracellular events indicated that cortical neurons treated with fosgo-AM exhibited a significant decrease in mitochondrial oxidative stress and cytochrome c release. Following Aß injury, fosgo-AM significantly enhanced activation of pro-survival effectors ERK and AKT, and reduced activity of GSK3ß, one of the main kinases involved in tau hyperphosphorylation. Fosgo-AM also mitigated Aß-induced deficits in Unc-like kinase 1 (ULK1) and Beclin-1, suggesting a potential effect on autophagy. Treatment with fosgo-AM protected cortical neurons from glutamate excitotoxicity, and such effects were abolished in the presence of an AKT or MEK/ERK inhibitor. In vivo, fosgonimeton administration led to functional improvement in an intracerebroventricular Aß25-35 rat model of AD, as it significantly rescued cognitive function in the passive avoidance test. Together, our data demonstrate the ability of fosgonimeton to counteract mechanisms of Aß-induced toxicity. Fosgonimeton is currently in clinical trials for mild-to-moderate AD (NCT04488419; NCT04886063).

Diabetic Foot Complications in Saudi Arabia: A Retrospective Study.

REVIEW: A common chronic health problem among Saudi Arabians is diabetes mellitus (DM). One of the most serious complications of diabetes is diabetic foot (DMF). AIM: The objective of this study was to identify the most common complications that develop among patients with DMF. In addition, we conducted a demographic analysis of chronic diabetic complications related to DMF. MATERIAL AND METHODS: The study involved 100 DMF attending the Jeddah clinic of Dr Soliman Fakeeh Hospital. Several chronic complications associated with DMF were reported, including peripheral arterial disease (PAD), coronary artery disease (CAD), retinopathy, nephropathy, and neuropathy. We examined the feet for ulcers, gangrene, amputations, bone deformities, Charcot joints, osteoarthritis, septic arthritis, and osteomyelitis. By using B-mode ultrasound and spectral Doppler imaging, we imaged the posterior tibial and anterior tibial arteries. RESULTS: People with poorly controlled diabetes mellitus type 2 (T2DM) are more likely to develop diabetic feet. The most common foot complications were foot ulcers (81%), foot amputations (31%), foot gangrene (29%) (29/100), bone deformities (22%) (22/100), ingrown toenails (17%) (17/100), Charcot's foot (10%) (10/100), and calluses (9%) (9/100). The majority of the patients suffered from hypertension and half had anaemia. Diabetic peripheral neuropathy affected about half of the patients, diabetic nephropathy affected one-third, and diabetic retinopathy affected 14%. Approximately a quarter (25/100) of the patients had CAD and less than half had PAD. There was atherosclerosis in 43% (43/100) of popliteal/infra-popliteal arteries. Twenty-two percent (22/100) of the anterior tibial arteries and 25% (25/100) of the posterior tibial arteries were stenotic or occluded. A biphasic mode was observed in 21% (21/100) of anterior tibial arteries, a monophasic mode in 9% (9/100), and a non-flowing mode in 3% (3/100). Twenty-three percent (23/100) of the posterior tibial arteries displayed biphasic Doppler modes, 5% (5/100) displayed monophasic modes, and 6% (6/100) displayed non-flowing modes. Conclusion: Diabetes foot is common among older males with poorly controlled T2DM. The most common foot complications were amputations, gangrene, foot ulcers, bone deformities, ingrown toenails, Charcot's foot, and calluses. Most DMF patients were anemic and hypertensive. Diabetes-related microvascular complications, such as diabetic peripheral neuropathy, nephropathy, and retinopathy, as well as macrovascular complications, such as coronary artery disease and peripheral arterial disease, were associated with DMF.