Symptomatic arteriovenous malformation of the thyroid/parathyroid gland: A case report.

Arteriovenous malformations (AVMs) are complex vascular lesions most commonly found in the brain and infrequently found in the head and neck. AVMs are characterized by a tangle of blood vessels called a nidus, which shunts blood from an artery directly to a draining vein. Various treatments are available, including surgical resection and endovascular embolization. Here, we report the case of a 32-year-old male patient who complained of painful pulsating left neck swelling with dysphagia for 1 year, which turned out to be an AVM alongside the left thyroid gland. The AVM was treated by embolization using Onyx in 2 sessions. The patient has been free of symptoms since the treatment.

The Prevalence of Depression in Patients With Epilepsy in the Kingdom of Saudi Arabia.

Objective Among patients with epilepsy (PWE), the prevalence of depression ranges from 30% to 50%, with a 5-25% prevalence of suicide. Depression and epilepsy affect daily tasks such as driving, employment, and physical activity. Depression is the most common comorbidity among patients with epilepsy. Because both conditions involve pathophysiological changes, treating mood disorders helps treat epilepsy and vice versa. Studies about epilepsy and depression in Saudi Arabia are scarce, and no study has been conducted on this topic at King Fahad Medical City (KFMC); hence, we aimed to determine the prevalence of depression among PWE who were followed up at KFMC. Methods This retrospective hospital-based study was conducted at KFMC in Riyadh, Saudi Arabia. This investigation spanned a period of 10 years, from 2008 to 2018. The study included patients with PWE who were diagnosed with depression. Results According to a study of individuals aged 18 to 69, 73.7% of patients had been diagnosed with chronic depression (i.e., for more than a year); most of these patients had completed elementary school. Higher rates of depression were also observed among elementary school pupils, divorced women, and non-Riyadh residents. A correlation was observed between the severity of depression based on the Patient's Health Questionnaire( PHQ-9) score, which was used to screen for depression and diabetes mellitus (DM), the number of antidepressant medications (ADM) used, the duration of antidepressant use, suicidal ideation or attempts, and the duration of depression. Epilepsy was most prevalent in the temporal lobe, accounting for 22.6% of all cases, and it was managed in 78.2% of the patients. The duration of epilepsy was significantly associated with the severity of depression.

Sensitivity, specificity, and accuracy of molecular profiling on circulating cell-free DNA in refractory or relapsed multiple myeloma patients, results of MM-EP1 study.

As a promising alternative to bone marrow aspiration (BMA), mutational profiling on blood-derived circulating cell-free tumor DNA (cfDNA) is a harmless and simple technique to monitor molecular response and treatment resistance of patients with refractory/relapsed multiple myeloma (R/R MM). We evaluated the sensitivity and specificity of cfDNA compared to BMA CD138 positive myeloma plasma cells (PCs) in a series of 45 R/R MM patients using the 29-gene targeted panel (AmpliSeq) NGS. KRAS, NRAS, FAM46C, DIS3, and TP53 were the most frequently mutated genes. The average sensitivity and specificity of cfDNA detection were 65% and 97%, respectively. The concordance per gene between the two samples was good to excellent according to Cohen's κ coefficients interpretation. An increased number of mutations detected in cfDNA were associated with a decreased overall survival. In conclusion, we demonstrated cfDNA NGS analysis feasibility and accuracy in R/R MM patients who may benefit from early phase clinical trial.

Retraction: Cerebral Venous Infarct After Recovery From COVID-19 Pneumonia.

[This retracts the article DOI: 10.7759/cureus.19763.].

Correlation of Transfusion Dependence and Its Associated Sequelae to Hematological and Biochemical Parameters in Patients With Sickle Cell Disease and Beta Thalassemia Major in Khobar: A Retrospective Study.

Sickle cell disease (SCD) and beta thalassemia major (ßTM) are multisystemic, genetically inherited diseases. They are caused by mutations of hemoglobin, which ultimately cause abnormal functioning of the red blood cells. The morbidity and mortality rates of these diseases are significant, as they may result in severe complications, some of which are quite fatal; hence, early diagnosis and treatment are crucial. The purpose of this study is to collect patients' data in terms of their manifestations and overall clinical picture and correlate them to the laboratory parameters with emphasis on their transfusion dependence and its sequelae in King Fahd Hospital of the University (KFHU), Al-Khobar, Saudi Arabia. After obtaining ethical approval from the institutional review board and in collaboration with the blood bank, patients' data were retrospectively collected from the hospital's database and categorized into two disease groups. Accordingly, data related to the biological and demographic information, clinical picture pattern, laboratory investigations, and therapeutic measures, with emphasis on blood transfusion as a treatment option, were gathered and analyzed. Eventually, the aforementioned data aspects were assessed for the probability of correlations, which were proven to be present to some level as an answer to our cohort study's question. Such findings, which will be depicted later in this study, might represent a ground for having a more comprehensive and extensive approach in terms of the general evaluation of patients with SCD and ßTM based on the established level of correlation. During the course of conducting our research, we encountered some limitations, including the sample size and scarce data available during the process of data collection.

Infections occurring following IL6 blockade for the management of cytokine release syndrome in onco-hematology patients.

BACKGROUND: Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some reports showed increased risk of bacterial infection in this context. In onco-hematology, there are few data about the occurrence of infection after administration of an anti-IL6/IL6R for CRS. METHODS: We retrospectively reviewed all consecutive patients treated in Gustave Roussy Cancer Campus between 2018 and 2021, who received anti-IL6/IL6R for CRS due to bsAb in phase I clinical trials or adoptive cellular therapy (ACT). We constituted a control group including all the patients treated in the same clinical trials or standard of care ACT, naïve of anti-IL6/IL6R. RESULTS: Fifty-two patients have been included. In the anti-IL6/IL6R group (n = 26), five patients developed a grade 2 to 5 infection within a month after anti-IL6/IL6R treatment, including two grade 5 infections. In the control group (n = 26), only one patient had a grade 3 infection. The two patients who had grade 5 infections were treated for diffuse large B cell lymphoma (DLBCL), one with bsAb and the other with CAR T cell. Fifty percent (3/6) of DLBCL patients who received an anti-IL6/IL6R presented an infection, one of which was a grade 5. In solid tumor patients treated with bsAb and anti-IL6/IL6R, only one patient (/9, 11%) developed a grade 2 viral infection. CONCLUSION: It seems that the use of anti-IL6/IL6R in CRS secondary to bsAb administration in solid tumors patients does not significantly increase the risk of infection, as opposed to DLBCL patients where secondary infection might be a concern.

Incidence, characteristics, management and outcome of patients with follicular lymphoma with tumor epidural compression, a study on 22 cases.

PURPOSE: Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression. MATERIAL AND METHODS: Observational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000-2021). RESULTS: Between 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range=[1-216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47-90%) of patients. The median PFS was of 36 months (95% CI 24-NA) and 5 years OS estimate was 79% (95% CI 62-100%). Two patients developed a relapse at a second epidural site. CONCLUSION: FL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro, and in silico mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, 1H NMR, 13C NMR, 13C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC50 at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC50 values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results.Communicated by Ramaswamy H. Sarma.

Exploring the dual effect of novel 1,4-diarylpyranopyrazoles as antiviral and anti-inflammatory for the management of SARS-CoV-2 and associated inflammatory symptoms.

COVID-19 and associated substantial inflammations continue to threaten humankind triggering death worldwide. So, the development of new effective antiviral and anti-inflammatory medications is a major scientific goal. Pyranopyrazoles have occupied a crucial position in medicinal chemistry because of their biological importance. Here, we report the design and synthesis of a series of sixteen pyranopyrazole derivatives substituted with two aryl groups at N-1 and C-4. The designed compounds are suggested to show dual activity to combat the emerging Coronaviruses and associated substantial inflammations. All compounds were evaluated for their in vitro antiviral activity and cytotoxicity against SARS-CoV infected Vero cells. As well, the in vitro assay of all derivatives against the SARS-CoV Mpro target was performed. Results revealed the potential of three pyranopyrazoles (22, 27, and 31) to potently inhibit the viral main protease with IC50 values of 2.01, 1.83, and 4.60 µM respectively compared with 12.85 and 82.17 µM for GC-376 and lopinavir. Additionally, in vivo anti-inflammatory testing for the most active compound 27 proved its ability to reduce levels of two cytokines (TNF-α and IL-6). Molecular docking and dynamics simulation revealed consistent results with the in vitro enzymatic assay and indicated the stability of the putative complex of 27 with SARS-CoV-2 Mpro. The assessment of metabolic stability and physicochemical properties of 27 have also been conducted. This investigation identified a set of metabolically stable pyranopyrazoles as effective anti-SARS-CoV-2 Mpro and suppressors of host cell cytokine release. We believe that the new compounds deserve further chemical optimization and evaluation for COVID-19 treatment.

Reactivation of Herpes Zoster in a Young Patient With Multiple Sclerosis Under Dimethyl Fumarate Treatment and Normal Lymphocyte Subsets Count: A Case Report.

Herpes zoster (HZ) infection results from the reactivation of the varicella-zoster virus (VZV), which remains dormant in the dorsal root ganglia after an initial chickenpox infection. Although HZ appears more common in people with multiple sclerosis (MS) than expected in the general population, few studies have investigated this association, particularly with a normal absolute lymphocyte count (ALC). Additionally, no reported cases have discussed the clinical presentation of such patients. This report describes the case of a 26-year-old female with a known history of relapsing-remitting MS on dimethyl fumarate (DMF) treatment. She presented with a history of painful erythematous blisters, diagnosed as acute HZ infection with a normal ALC. This case provides evidence that warrants further research and attention to the management of patients with MS receiving DMF, particularly regarding infectious risks. It highlights the importance of pharmacovigilance and the potential benefits of VZV and HZ immunization in DMF recipients.

Innovative Reconstructive Management of Foot Macrodactyly in a Pediatric Patient: A Case Report.

Macrodactyly is a rare congenital anomaly characterized by disproportionate hypertrophy of one or more digits or the forefoot, involving some or all tissue types. It is nonhereditary and can present alone or alongside other deformities. Usually, macrodactyly is treated with amputation of the affected toe or finger to reduce the chance of recurrence. In this paper, we present the case of a child with macrodactyly who was treated successfully without amputation and instead with a reconstruction of the toe shape to resemble a near-natural-looking toe with intact functions. The patient was a one-year-old female who presented with macrodactyly of her right great toe, right second toe, and forefoot. She had no history of other congenital deformities or systemic diseases. A reconstruction surgery was performed, which involved debulking the right great toe, right second toe, and forefoot. Also, it included the creation of the first web space and the restoration of the nailbed of the second toe. Postoperative follow-up revealed minimal complications. Thus, a second reconstructive surgery was performed, which included debulking and further reconstruction of the foot to improve the result. Several techniques exist for the reduction of macrodactyly that can achieve optimal results. The choice of technique depends on the specifics of the case and the experience of the surgeon. We therefore hope our technique will be beneficial for the management of future cases of macrodactyly. One year of follow-up after the second operation revealed maintained function and no regrowth recurrence.

In vitro and computational investigations of novel synthetic carboxamide-linked pyridopyrrolopyrimidines with potent activity as SARS-CoV-2-MPro inhibitors.

An essential target for COVID-19 is the main protease of SARS-CoV-2 (Mpro). With the objective of targeting this receptor, a novel set of pyrido[1,2-a]pyrrolo[2,3-d]pyrimidines with terminal carboxamide fragments was designed, synthesized, and considered as an initial motif for the creation of effective pan-coronavirus inhibitors. Accordingly, nine derivatives (21-29) have been introduced for in vitro assay to evaluate their antiviral activity and cytotoxicity effect against COVID-19 virus using Vero cells. The obtained data revealed that the majority of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with weak or even no detectable cytotoxic effect on Vero cells. Extensive molecular docking simulations highlighted proper non-covalent interaction of new compounds within the binding pocket of Mpro as a potential target for their antiviral activity. In vitro assay for all the synthesized derivatives against the viral Mpro target indicated that compounds 25 and 29 have promising inhibitory activity with IC50 values at low micromolar concentrations. The molecular dynamic simulation results predicted the stability of compound 29 in the binding cavity of SARS-CoV-2 Mpro and hence supported the high inhibitory activity shown by the In vitro assay. These results suggested that compounds 25 and 29 merit further investigations as promising drug candidates for the management of SARS-CoV-2.

Design and Synthesis of Benzene Homologues Tethered with 1,2,4-Triazole and 1,3,4-Thiadiazole Motifs Revealing Dual MCF-7/HepG2 Cytotoxic Activity with Prominent Selectivity via Histone Demethylase LSD1 Inhibitory Effect.

In this study, an efficient multistep synthesis of novel aromatic tricyclic hybrids incorporating different biological active moieties, such as 1,3,4-thiadiazole and 1,2,4-triazole, was reported. These target scaffolds are characterized by having terminal lipophilic or hydrophilic parts, and their structures are confirmed by different spectroscopic methods. Further, the cytotoxic activities of the newly synthesized compounds were evaluated using in vitro MTT cytotoxicity screening assay against three different cell lines, including HepG-2, MCF-7, and HCT-116, compared with the reference drug Taxol. The results showed variable performance against cancer cell lines, exhibiting MCF-7 and HepG-2 selectivities by active analogs. Among these derivatives, 1,2,4-triazoles 11 and 13 and 1,3,4-thiadiazole 18 were found to be the most potent compounds against MCF-7 and HepG-2 cancer cells. Moreover, structure-activity relationship (SAR) studies led to the identification of some potent LSD1 inhibitors. The tested compounds showed good LSD1 inhibitory activities, with an IC50 range of 0.04-1.5 µM. Compounds 27, 23, and 22 were found to be the most active analogs with IC50 values of 0.046, 0.065, and 0.074 µM, respectively. In addition, they exhibited prominent selectivity against a MAO target with apparent cancer cell apoptosis, resulting in DNA fragmentation. This research provides some new aromatic-centered 1,2,4-triazole-3-thione and 1,3,4-thiadiazole analogs as highly effective anticancer agents with good LSD1 target selectivity.

Green synthesis of gold nanoparticles in Gum Arabic using pulsed laser ablation for CT imaging.

Laser ablation synthesis in liquid solution (PLAL) is a green technique that allows for the physical formation of nanomaterials. This study indicates the preparation of stable gold nanoparticles (AuNPs) in Gum Arabic (GA) solution via laser ablation as a CT contrast agent. The optical properties were achieved using the absorption spectroscopic technique whereas the morphology and size distribution were investigated by TEM and ImageJ software. TEM image shows greater stability and spherical shape of GA-AuNPs with smaller size at 1.85 ± 0.99 nm compared to AuNPs without GA. The absorption spectrum of pure AuNPs has a lower absorption peak height in the visible range at λ = 521 nm, while the spectrum of GA-AuNPs has a higher plasmon peak height at λ = 514 nm with a blue shift towards lower wavelengths. The concentration of GA that dissolved in 10 mL of DI water via laser ablation is set at 20 mg. Increasing the number of pulses has only a minor effect on particle size distribution, which remains tiny in the nanometer range (less than 3 nm). For energies greater than 200 mJ, there is a blue shift toward shorter wavelengths. As the concentration of GA-AuNPs increases, the CT number is also increased indicating good image contrast. It can be concluded that there is a positive and significant influence of GA as a reducing agent for AuNPs, and a contrast agent for CT imaging which highlights its superiority in future medical applications.

Risk factors for complicated Mohs surgery in the South Sweden Mohs Cohort.

BACKGROUND: Mohs micrographic surgery (MMS) is a precise, tissue-sparing surgical technique that offers superior cure rates compared to traditional surgical excision. However, the degree of difficulty of MMS depends on many variables, and consequently, the number of surgical stages required for each case is quite unpredictable. OBJECTIVES: To identify risk factors for complicated MMS, defined as MMS requiring ≥3 stages. METHODS: In a cohort study design, data were prospectively collected from 612 patients that underwent MMS for basal cell carcinoma (BCC) at the Department of Dermatology, Skåne University Hospital, Lund, between 2009 and 2020. Univariate and multivariate logistic regression were used to estimate the risk of MMS requiring ≥3 stages. Due to the risk of multicollinearity between recurrent or incompletely excised BCC and previous treatments, a partially and a fully adjusted multivariate logistic regression model were constructed. RESULTS: In fully adjusted multivariate analyses, age (odds ratio (OR) 1.02; confidence interval (CI) 95% 1.00-1.04), previous cryotherapy (OR 2.3; CI 95% 1.1-4.8), and >1 previous surgery (OR 3.4; CI 95% 1.5-7.7) were significantly associated with risk of complicated MMS. Recurrent BCC was associated with the risk of complicated MMS in partially adjusted multivariate analyses, but not in the fully adjusted analyses. In this highly selected cohort, histopathological subtype, and tumour localization were not associated with the risk of complicated MMS. CONCLUSIONS: Older age and tumours previously treated with cryotherapy or multiple prior surgeries increased the risk of MMS requiring ≥3 stages. Whether recurrent BCC is an independent risk factor for complicated MMS needs further evaluation. Knowledge of these risk factors may ameliorate the planning of Mohs surgeries.

Cerebral Venous Infarct After Recovery From COVID-19 Pneumonia.

The coronavirus disease 2019 (COVID-19) may have multisystem organ involvement. Thrombotic events are well-recognized complications of COVID-19. Such complications may include the pulmonary, renal, and other organs vasculature. The risk of coagulopathy is usually related to the severity of COVID-19 pneumonia. Few cases suggested that the coagulopathy risk may persist for some period after the recovery from COVID-19. We report the case of a middle-aged man with severe COVID-19 pneumonia that required seven days of endotracheal intubation and mechanical ventilation who presented with headache and left-sided weakness that occurred three days after his discharge. A computed tomography scan was performed to rule out intracranial hemorrhage before initiating the thrombolytic therapy. The scan demonstrated hemorrhage in the right temporal lobe with surrounding vasogenic edema along with density in the right transverse sinus. Subsequently, computed tomography venography was performed and demonstrated the filling defect representing right sigmoid venous sinus thrombosis. The patient received conservative measures in the form of intravenous hydration, anticoagulation, analgesics, and anticonvulsants. During the hospital stay, the patient had improvement in his symptom and mild neurological deficit persisted. The case highlighted that risk of thrombotic complications in COVID-19 pneumonia may persist for some period after the recovery from the disease. Hence, thromboprophylaxis may be indicated in selected patients with a risk of thrombotic events after their recovery from severe COVID-19.

Reversible Cerebral Vasoconstriction Syndrome in a Background of Eclampsia Responding to Milrinone Infusion.

BACKGROUND Reversible cerebral vasoconstriction syndrome (RCVS) is a rare neurological disorder with a complex physiopathology that is not fully understood. Suggested underlying mechanisms include failure of autoregulation, endothelial dysfunction, and oxidative stress. It is characterized by reversible multifocal constriction of the cerebral arteries, and can be triggered by many conditions, including, vasoactive medications (eg, triptans), cerebrovascular events, primary headache disorders, and metabolic causes (eg, hypercalcemia). RCVS can also be associated with pregnancy-related conditions, such as thrombotic thrombocytopenic purpura, eclampsia, and pre-eclampsia. Thunderclap headache is the most common clinical manifestation; however, other symptoms can result from complications of the disease, such as stroke, brain edema, and seizures. Several case reports have been published of an association between RCVS and eclampsia, but to the best of our knowledge, only 3 cases were successfully treated with intravenous milrinone and this is the only patient reported in Saudi Arabia. CASE REPORT We report a case of 25-year-old primigravida woman who presented with acute-onset headache, nausea, elevated blood pressure, and generalized tonic clonic seizure. She was diagnosed as having RCVS secondary to eclampsia based on clinical and radiological features. She was initially started on nimodipine, which is usually the first-line management of RCVS, as well as magnesium sulfate and levetiracetam; however, she only achieved full recovery after starting intravenous milrinone. CONCLUSIONS Milrinone is one of the emerging drugs for treatment of RCVS, and this case report delineates the potential of using the drug, especially in cases refractory to standard therapy.

Huge Concha Bullosa Involved With Allergic Fungal Sinusitis and Mimicking a Bony Tumor.

Concha bullosa (CB) is a pneumatized air cell within the nasal turbinates, often in the middle turbinate. CB is one of the most common anatomical variations found in the middle turbinate. It generally tends to be asymptomatic but can cause symptoms such as nasal obstruction, facial pain, and a decrease in the sense of smell. Moreover, CB can be involved in chronic rhinosinusitis, which can lead to its confusion with other lesions, as the radiographic picture might mimic other nasal pathologies. Here, we report a case of massive CB involved with allergic fungal sinusitis (AFS) and mimicking a bony tumor in order to highlight the diagnostic challenge of this clinical entity.