Rigidity and Flexibility of Pyrazole, s-Triazole, and v-Triazole Derivative of Chloroquine as Potential Therapeutic against COVID-19

Based on the core unit of chloroquine, new types of N-heterocyclic compounds that are fused together have been made. The compounds were put into two groups. In series A, the five-member hetero-rings were directly connected to the core unit, while in series B, the CH2 group was used to make the five-member ring more flexible (series B). Using the Gaussian 09 programme, the DFT method with hybrid correlation functional (B3LYP) and 6-311 (d, p) basis sets were used to figure out how to optimize and measure the quantum chemical properties of molecules. The molecular overeating environment (MOE) programme is used to study molecular docking. The binding of flexible compounds shows that AC8, AC10, AC3, and AC5 have the strongest binding affinities compared to the other candidates, while the rigid molecules ARC10 and ARC6 have the lowest binding affinities. In general, the results of the binding affinity showed that the drugs and receptors being studied might have anti-Covid-19 properties. Likewise, the flexible compounds AC8, AC10, AC3, and AC5 had the lowest Ki values of those made and could be used as a treatment. Our virtual physicochemical evaluation of all compounds in series A and B showed that all of them met the limits for molecular weight, lipophilicity (MLogP 4.15, the octanol-water partition coefficient), and water solubility. In addition to MR, the number of H-bond acceptors and the PSA were both within the acceptable range. It seems that the number of rotatable bonds is the only physicochemical property that separates the compounds in series B. The scores of compounds AC3, AC4, AC7, AC8, AC11, and AC12 are outside the acceptable range when compared to the results of chloroquine as the parent compound. © 2023 by SPC (Sami Publishing Company).

Alternative bisphosphonates for the treatment of bilateral hip joint heterotopic ossification with bleeding risk

Context: A 40-year-old female with recently diagnosed seronegative anti-phospholipid syndrome precipitating multiple ischemic events including a spinal cord infarction and a cerebrovascular accident intractable to warfarin use complicated by abdominal bleeds and multiple intramuscular hematomas was admitted to acute inpatient rehabilitation for subdural hematoma after fall while on apixaban with concurrent diagnosis of ventilator dependent COVID-19 status post extubation. Finding(s): She was found to have extensive, active heterotopic ossification (HO) on bilateral hips shown on triple phase bone scan. She was trialed on indomethacin 25 mg TID, but the patient developed a subsequent right lower limb intramuscular expanding hematoma at the site of a prior hematoma. She was put on full dose enoxaparin for treatment for the antiphospholipid syndrome and the nonsteroidal antiinflammatory drug was discontinued at that time. Switching to warfarin for co-treatment of HO and antiphospholipid syndrome was not pursued, as she had had previous treatment failures for anti-phospholipid syndrome and would have put her again at risk for breakthrough reinfarction. Conclusion/Clinical Relevance: The patient was treated with alendronate 70 mg once weekly. Etidronate, the mainstay treatment for HO, is no longer available in the US. Alternative bisphosphonates, such as clodronate, are also unavailable in the US. Pamidronate only halts secondary progression post-surgically. Alendronate may serve as a potential bisphosphonate for the treatment of HO. In this complicated case of bilateral hip HO in the setting of bleeding and clotting risks, where NSAIDs and warfarin were contraindicated, the recourse was to use an alternative bisphosphonate, alendronate, to diminish further bony matrix remodeling.

Association between Administration of Systemic Corticosteroids and the Recovery of Olfactory and/or Gustatory Functions in Patients with COVID-19: A Prospective Cohort Study

AIM: This study is a prospective cohort study aimed to assess the effect of systemic corticosteroids administration time in the recovery of gustatory and olfactory sensations dysfunction (ageusia and anosmia) in COVID-19 patients. MATERIALS AND METHODS: Sixty-seven COVID-19 patients with symptoms of ageusia and anosmia were recruited (that their COVID infection was confirmed using polymerase chain reaction). Daily 10 mg of systemic corticosteroids were prescribed in the 1st week and then reduced to 5 mg in the 2nd week to all the patients to observe taste and smell sensation recovery. All data were recorded and then analyzed. Patients were then grouped into two groups (early and late groups) according to the duration of their taste and smell dysfunction. RESULTS: Regression analysis showed that early corticosteroid administration resulted in a significant decrease in recovery time of ageusia and anosmia (0.27 [0.2–0.35], p < 0.001). Patients in the early administration group (<1 week) showed faster improvement in regaining taste and smell functions than in the late administration group (>1 week) with significant difference (p < 0.001). CONCLUSIONS: The use of systemic corticosteroids in early phases of covid-19 infection help in faster recovery of ageusia and anosmia.

Covid-19 in recipients of living donor liver transplantation: a worse or an equivalent outcome?

BACKGROUND: Coronavirus disease 2019 (Covid-19) pandemic is representing a massive burden to the community with the new virus. There is few data regarding Covid-19 in liver transplant patients. Concerns were raised regarding the course of the disease in transplanted patients due to immunosuppression and risk of hepatic injuries. AIM: To describe the outcomes of Covid-19 infection in recipients of living-donor liver transplantation (LDLT). METHODS: Retrospective analysis of 41 recipients of LDLT diagnosed with Covid-19 by real-time PCR or CT chest criteria of Covid-19 between April 2020 and April 2021. This Cohort was derived from Ain Shams Center for Organ Transplantation database, Ain Shams Specialized Hospital, Cairo, Egypt, which is considered one of the largest centers of LDLT in the Middle East. Patients were classified to mild, moderate, severe and critics according to clinical classification released by the National Health Commission of China. RESULTS: A total of 41 patients and 2 patients with reinfection were included in this cohort with mean age 54 years with 74% male and 26% female. The body mass index ranged from 19.3 to 37. About 30% were described as a mild case, 46.5% were moderate, 14% were severe and 9% were critical cases. Two cases developed infection twice. Total of 20 patients (46.5%) were managed in home isolation setting, 17 patients (39.5%) needed admission to ward, 4 patients (9%) in intermediate care unit and 2 patients (4%) admitted to intensive care unit. About 60% of cases were on room air, only 3 patients needed invasive methods, 2 patients needed face mask and 1 case needed invasive CPAP. In total, 41 patients recovered (95%) and 2 patients (5%) died; 1 was Covid related and the other one was non-Covid related. Female gender, higher BMI and hypertension were associated with severe course of the disease. CONCLUSION: In the setting of LDLT, the possibilities of catching Covid-19 infection are high due to chronic immunosuppression use. Yet, the outcome of infection in term of morbidity and the needs for hospital admission or intensive care is generally matched to general population.

The effect of chronic anticoagulation and antiplatelets on COVID-19 infection

Background : Severe acute respiratory syndrome coronavirus -2 caused by the novel coronavirus 2019 (Covid-19) has resulted in a global pandemic. Covid-19 disease is associated with a hypercoagulable state, leading to microvascular and/or macrovascular thrombosis. The role of anticoagulation in Covid-19 is debatable. Aims : To compare outcomes of chronic anticoagulation and/or antiplatelets versus no chronic anticoagulation or antiplatelets in Covid-19 patients. Methods : This is a retrospective cohort study of hospitalized patients with polymerase chain reaction confirmed Covid-19 and over the age of 18 years who presented to the Trinity Health hospitals from March 8, 2020, to May 15, 2020. The exposed group was defined as patients who received chronic anticoagulation (warfarin, direct oral anticoagulant) or antiplatelet therapy or both(for more than one-month duration) for reasons other than Covid-19 disease while control group patients were defined as those who did not receive these therapies prior to admission. The primary outcome of the study is a composite outcome to compare mortality, length of hospital stay, readmission rate, rate of intubation, and length of Intensive-Care-Unit admission. Baseline characteristics and Covid-19 related treatment were compared in both groups (Table 1). The chi-square test and the student's t -test were used to compare the outcome in both groups. Statistical analysis was performed using SPSS version 25. Results : There were 3180 patients who were Covid-19 positive during the study period;452 patients met the inclusion criteria. There were 183 patients in the exposed group and 269 patients in the control group. In the exposed group there was a significantly higher three-months mortality rate (30.6% vs. 16%;P < 0.0005) compared to the control group. There were no significant associations between readmission rate, rate of intubation, length of hospital stay, and length of ICU stay by the group. Conclusions : Our results showed higher mortality in patients on chronic anticoagulation or antiplatelet therapy.