Functional outcomes of COVID-19 patients with acute ischemic stroke: A prospective,observational, single-center study in North Jordan

We assessed whether stroke severity, functional outcome, and mortality in patients with ischemic stroke differed between patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and those without.We conducted a prospective, single-center cohort study in Irbid, North Jordan. All patients diagnosed with ischemic stroke and SARS-CoV-2 infection were consecutively recruited from October 15, 2020, to October 16, 2021. We recorded demographic data, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, stroke subtype according to the Trial of ORG 10172 in Acute Stroke Treatment Criteria (TOAST), treatments at admission, and laboratory variables for all patients. The primary endpoint was the functional outcome at 3 months assessed using the modified Rankin Score. Secondary outcomes involved in-hospital mortality and mortality at 3 months.We included 178 patients with a mean (standard deviation) age of 67.3 (12), and more than half of the cases were males (96/178; 53.9%). Thirty-six cases were coronavirus disease 2019 (COVID-19) related and had a mean (standard deviation) age of 70 (11.5). When compared with COVID-19-negative patients, COVID-19-positive patients were more likely to have a higher median NIHSS score at baseline (6 vs 11; P = .043), after 72 hours (6 vs 12; P = .006), and at discharge (4 vs 16; P < .001). They were also more likely to have a higher median modified Rankin Score after 3 months of follow-up (P < .001). NIHSS score at admission (odds ratio = 1.387, 95% confidence interval = 1.238–1.553]; P < .001) predicted having an unfavorable outcome after 3 months. On the other hand, having a concomitant SARS-CoV-2 infection did not significantly impact the likelihood of unfavorable outcomes (odds ratio = 1.098, 95% confidence interval = 0.270–4.473; P = .896).The finding conclude that SARS-CoV-2 infection led to an increase in both stroke severity and in-hospital mortality but had no significant impact on the likelihood of developing unfavorable outcomes.     

The antimicrobial peptide alpha defensin correlates to type 2 diabetes via the advanced glycation end products pathway

BackgroundDiabetes is a serious health problem that results in high mortality rates worldwide. α-defensins are antimicrobial peptides of the innate immune system that contribute to inflammation. However, data on serum levels of α-defensin in patients suffering from type 2 diabetes are limited.ObjectivesThis study aimed to assess the possible changes in α-defensin serum levels in patients suffering from type 2 diabetes and to investigate its correlation with relevant biomarkers.MethodologyAnalysis of serum α-defensin levels in 47 type 2 diabetics with diabetic neuropathy, 19 type 2 diabetics with no complications and 19 healthy control subjects by enzyme-linked immunosorbent assay was established. Furthermore, measurement of advanced glycation end products (AGEs) and fasting blood glucose (FBG) serum levels was performed, together with the lipid profile analysis.ResultsThe serum levels of α-defensin were higher in patients with and without diabetic neuropathy in comparison to control subjects. In addition, there was a significant correlation between α-defensin serum levels and AGEs and FBG serum levels as well as with the body mass index.Conclusionsα-defensins are significantly elevated in serum of type II diabetics, and correlate with AGEs serum levels indicating a crosstalk that may aggravate inflammation in type 2 diabetes.     

Comparative evaluation of the efficacy of topical tacrolimus 0.03% and topical calcipotriol 0.005% mixed with betamethasone dipropionate versus topical clobetasol 0.05% in treatment of alopecia areata: A clinical and trichoscopic study

Background

Alopecia areata (AA) is a common non-scarring hair loss disorder that affects children and adults with a great psychological burden because of its recurrent and sometimes treatment-refractory nature.

Objective

To compare the efficacy of topical calcineurin inhibitor, topical potent steroid combined with vitamin D analogue versus topical superpotent steroid in treatment of localized AA.

Patients and Methods

Sixty subjects with chronic (>1 year) localized (SALT score < 25%) AA, confirmed clinically and dermoscopically, were randomized into three groups. Group I used topical 0.03% tacrolimus (Tarolimus®), group II used topical potent steroid combined with vitamin D analogue (Daivobet®). and group III used topical superpotent steroid (Dermovate®). All patients continued a daily therapy for three successive months and were followed up for three other months. Assessment was done using PULL test, SALT score, and dermoscopic comparison before and after therapy.

Results

Group II showed comparable statistical results to group III with lower values in a non-statistically significant way. Group I achieved the least improvement among all groups.

Conclusion

Combined vitamin D analogues with potent steroid appears to be a more convenient treatment for localized AA than superpotent steroids because of less side effects and comparable efficacy. Tacrolimus needs further research or formula customization to be used as a topical therapy for AA.     

Rapid high performance liquid chromatography method for erlotinib quantification in vitro: Application to study the effect of resveratrol on metabolism and cellular uptake of erlotinib

Background: Erlotinib is a selective epidermal growth factor receptor inhibitor that is used for the treatment of non-small cell lung cancer and pancreatic cancer. Its metabolism is mainly mediated by cytochrome P450 3A (CYP 3A). Resveratrol, a natural compound found in many plants and supplements, is known to inhibit CYP3A enzyme, therefore, it may act as an inhibitor for the metabolism of erlotinib. Objective: Development of a rapid high performance liquid chromatography with photodiode array detection (HPLC-PDA) method for the quantification of erlotinib in liver microsomes and cancer cells and its application to study resveratrol effect on metabolism and cellular uptake of erlotinib. Methods: HPLC-PDA was used to develop an efficient bioanalytical method with a 2.5-min runtime preceded by a simple protein precipitation step. The method was validated according to the European Medicines Agency guidelines. Erlotinib metabolic stability and resveratrol effect on erlotinib metabolite formation were evaluated in rat liver microsomes. Furthermore, the method was used to measure the intracellular concentrations of erlotinib in cancer colorectal cells and investigating resveratrol effect on the cellular uptake of erlotinib. Results: A rapid HPLC-PDA method was developed and validated for the first time to address potential drug interaction of erlotinib with resveratrol. Resveratrol was a strong inhibitor of erlotinib metabolism in vitro with IC₅₀ = 4.03 μM. Resveratrol, however, had no effect on erlotinib cellular uptake after 1 h incubation in human colorectal cancer cells. Conclusion: The study suggests that resveratrol may produce a potential herb–drug interaction with erlotinib at the metabolism level and should be investigated in patients in the clinic.     

Infertility,pregnancy and breastfeeding in kidney transplantation recipients: Key issues

Chronic kidney disease (CKD), especially in advanced stages, is an important cause of infertility. In CKD patients, infertility has been linked to multiple factors. The pathophysiology of infertility related to CKD is complex and forked. Correction of modifiable factors can improve fertility in both genders. In males as well as females, successful kidney transplantation offers good chances of restoration of reproductive function. In female renal allograft recipients, recovery of reproductive functions in the post-transplant period will manifest as restoration of normal menses and ovulation. Owing to this improvement, there is a significant risk of unplanned pregnancy, hence the need to discuss methods of contraception before transplantation. In kidney transplant recipients, different contraceptive options for pregnancy planning, have been used. The selection of one contraception over another is based on preference and tolerability. Pregnancy, in renal transplanted females, is associated with physiologic changes that occur in pregnant women with native kidneys. Immunosuppressive medications during pregnancy, in a recipient with a single functioning kidney, expose the mother and fetus to unwanted complications. Some immunosuppressive drugs are contraindicated during pregnancy. Immunosuppressive medications should be discussed with renal transplant recipients who are planning to breastfeed their babies. In addition to antirejection drugs, other medications should be managed accordingly, whenever pregnancy is planned.     

A comparative study between angiotensin receptor neprilysin inhibitor (thiorphan/irbesartan) with each of nitrate and carvedilol in a rat model of myocardial ischemic reperfusion injury

The combined angiotensin receptor neprilysin inhibitor is a promising cardioprotective pharmacological agent. This study investigated the beneficial effects of thiorphan (TH)/irbesartan (IRB), in myocardial ischemia–reperfusion (IR) injury, compared to each of nitroglycerin and carvedilol. Male Wistar rats were divided into five groups (10 rats/group): Sham, untreated I/R, TH/IRB + IR (0.1/10 mg/kg), nitroglycerin + IR (0.2 mg/kg), and carvedilol + IR (10 mg/kg). Mean arterial blood pressure, cardiac functions and arrhythmia incidence, duration and score were assessed. Cardiac levels of creatine kinase-MB (CK-MB), oxidative stress, endothelin-1, ATP, Na⁺/K⁺ ATPase pump activity and mitochondria complexes activities were measured. Histopathological examination, Bcl/Bax immunohistochemistry studies and electron microscopy examination of left ventricle were performed. TH/IRB preserved the cardiac functions and mitochondrial complexes activities, mitigated cardiac damage, reduced oxidative stress and arrhythmia severity, improved the histopathological changes and decreased cardiac apoptosis. TH/IRB showed a comparable effect to each of nitroglycerin and carvedilol in alleviating the IR injury consequences. TH/IRB showed significant preservation of mitochondrial complexes activity I and II compared to nitroglycerin. TH/IRB significantly increased LVdP/dtmax and decreased oxidative stress, cardiac damage and endothelin-1 along with increasing the ATP content, Na⁺/K⁺ ATPase pump activity and mitochondrial complexes activity when compared to carvedilol. TH/IRB showed a cardioprotective effect in reducing IR injury that is comparable to each of nitroglycerin and carvedilol that could be explained in part by its ability to preserve mitochondrial function, increase ATP, decrease oxidative stress as well as endothelin 1.     

Human phase-I metabolism and prevalence of two synthetic cannabinoids bearing an ethyl ester moiety: 5F-EDMB-PICA and EDMB-PINACA

Around 2017, with the appearance of 5F-EDMB-PINACA, synthetic cannabinoids (SCs) carrying an ethyl ester moiety at the linked group started spreading on the market of new psychoactive substances (NPS). In 2020 and 2021, the indole analog of 5F-EDMB-PINACA (5F-EDMB-PICA) and the non-fluorinated analog of this compound (EDMB-PINACA) were analytically characterized. Here, we present suitable urinary markers to prove the consumption of these two ethyl analogs. Ten authentic urine samples for each compound were analyzed by liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-qToF-MS). Anticipated phase-I metabolites detected in urine samples were confirmed in vitro by applying a pooled human liver microsomes (pHLM) assay. Prevalence data were obtained from urines collected for abstinence control and submitted to a screening method for SC metabolites. Ten phase-I metabolites of 5F-EDMB-PICA and 18 of EDMB-PINACA were detected by LC-qToF-MS analysis of authentic urine specimens. The main in-vivo metabolites were built by ester hydrolysis, often coupled to further metabolic processes. Investigation of phase-I biotransformation led to the identification of ester hydrolysis, monohydroxylation, and defluorination products as the most suitable urinary biomarkers for 5F-EDMB-PICA. Metabolites formed by ester hydrolysis coupled to ketone formation and by monohydroxylation are suggested for the detection of EDMB-PINACA. From October 1, 2020 to February 1, 2022, among positive urine samples, 5.4% and 10.1% tested positive 5F-EDMB-PICA and EDMB-PINACA, respectively. Due to common metabolites shared among structurally related SCs, the unequivocal detection of their consumption remains challenging for forensic laboratories and requires sensitive methods to monitor multiple metabolites, ideally including highly specific species.     

Effect of preoperative tramadol,ibuprofen, ibuprofen/acetaminophen on the anaesthetic efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis

The purpose of this double-blind clinical trial was to compare the effect of preoperative tramadol 50 mg, tramadol 100 mg, ibuprofen 600 mg, ibuprofen 600 mg/acetaminophen 1000 mg or placebo 60 min before the administration of inferior alveolar nerve blocks (IANB) of mandibular teeth in patients experiencing symptomatic irreversible pulpitis (SIP). Two hundred and fifty emergency patients diagnosed with SIP were randomly divided into five groups and received medications. Endodontic access was begun 15 min after completion of the IANB, and all patients had profound lip numbness. The Heft-Parker visual analogue scale was used to evaluate pain. Premedication with tramadol 100 mg significantly increased the success rate to 62% than the other groups (p < 0.05). The success rates of ibuprofen, ibuprofen/acetaminophen and tramadol 50 mg groups were not significantly different (p > 0.05). Premedication with tramadol 100 mg enhanced the anaesthetic success of IANB in mandibular molars with SIP.