Successful Recovery of COVID-19 Associated With Cardiomyopathy in Advanced Breast Cancer Patient With Pulmonary Lymphangitis Carcinomatosis.

SARS-CoV-2 infection induces myocardiopathy in 19% of severe cases, with a mortality rate of up to 51%. The mainstay of treatment is supportive care, steroids, and tocilizumab (anti-IL-6). This is a case of a 43-year-old woman diagnosed with hormone-positive breast cancer with lung metastasis and pulmonary lymphangitis carcinomatosis (PLC). Her baseline cardiac function was within normal limits. She presented to the emergency department with respiratory distress. Chest CT showed multiple bilateral ground-glass opacities consistent with COVID-19 pneumonia and confirmed by COVID-19-PCR nasal swab. Her condition deteriorated, and she was urgently admitted to the intensive care unit with evidence of a cytokine storm. She was started on tocilizumab, dexamethasone, and meropenem. Echocardiogram (echo) showed a severely reduced ejection fraction with severe global hypokinesis. A second dose of tocilizumab was given, and the dexamethasone dose was increased. Fortunately, the patient had significant clinical and biochemical improvement and regained her normal cardiac function. In conclusion, dexamethasone and tocilizumab could be promising aids in treating cardiomyopathy secondary to SARS-CoV-2 infection.

Hematologic Manifestations of Parvovirus B19 Infection.

Parvovirus B19 virus infection is widespread among humans because of its highly infectious and obstinate nature, with up to 80% of the population testing positive for IgG antibodies against the virus. Pronormoblasts observed in biopsy are the hallmarks of PVB19 infection. In addition, PVB19 affects the skin, heart, brain, joints, and liver and can be diagnosed through antibody detection or DNA detection via PCR. Due to its capsid proteins' high affinity for bone marrow receptors, its main presentation is the suppression of bone marrow functions. It has been shown to affect patients with hemolytic anemia and patients with hematological malignancies, presenting with pure red cell aplasia. The main available effective treatment option is IV immunoglobulins; however, the risk of recurrence remains high after treatment.

Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia.

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

An insight into the discovery, clinical studies, compositions, and patents of macozinone: A drug targeting the DprE1 enzyme of Mycobacterium tuberculosis.

Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1) inhibitors are an innovative and futuristic orally active group of antituberculosis agents. A few DprE1 inhibitors are in the clinical trial for tuberculosis (TB), including macozinone. This review highlights the discovery, developmental status, clinical studies, patents, and prospects of macozinone (MCZ). The patent and non-patent literature search was done by entering keywords such as macozinone; MCZ; PBTZ169; PBTZ-169 in Pubmed, Espacenet, Patentscope, and the USPTO databases. However, data on Sci-Finder was searched using CAS registry number: 1377239-83-2. MCZ clinical trial studies were retrieved from the clinicaltrials.gov database using the exact keywords. The chemical structure of MCZ was disclosed in 2009. Accordingly, patents/patent applications published from 2009 to June 12, 2022, have been discussed herein. MCZ and MCZ hydrochloride salt patents were granted in 2014 and 2019, respectively, in the USA. The patent literature and the clinical trial studies suggest capsule, tablet, and suspension formulations of crystalline MCZ and its hydrochloride salt as the possible and prospective dosage forms to treat TB. Some combinations of MCZ with other drugs (chloroquine, telacebec, tafenoquine, TBI-166, and sanfetrinem) with improved anti-TB efficacy have been documented. Based on the literature covered in this review article on the clinical studies and patents applied/granted to MCZ, it can be inferred that MCZ seems to be a promising DprE1 inhibitor and could help to tackle the emerging dilemma of drug-resistant either as a monotherapy or in combination with additional anti-TB agents. Furthermore, the authors anticipate the development of new combinations, salts, and polymorphs of MCZ as anti-TB agents shortly. This review article might prove beneficial to the scientific community as it summarizes chemistry, pharmacology and provides an update on the clinical studies and patents/patent applications of one of the emerging anti-TB drugs in one place.

A Glance at the Development and Patent Literature of Tecovirimat: The First-in-Class Therapy for Emerging Monkeypox Outbreak.

Monkeypox disease (MPX) is currently considered a global threat after COVID-19. European Medicines Agency (EMA) approved Tecovirimat in capsule dosage form (200 mg) as the first treatment for MPX in January 2022. This article highlights Tecovirimat's development and patent literature review and is believed to benefit the scientists working on developing MPX treatments. The literature for Tecovirimat was gathered from the website of SIGA Technologies (developer of Tecovirimat), regulatory agencies (EMA, United States Food and Drug Administration (USFDA), and Health Canada), PubMed, and freely accessible clinical/patent databases. Tecovirimat was first recognized as an anti-orthopoxvirus molecule in 2002 and developed by SIGA Technologies. The USFDA and Health Canada have also recently approved Tecovirimat to treat smallpox in 2018 and 2021, respectively. The efficacy of Tecovirimat was verified in infected non-human primates (monkeys) and rabbits under the USFDA's Animal Rule. Most clinical studies have been done on Tecovirimat's safety and pharmacokinetic parameters. The patent literature has revealed inventions related to the capsule, injection, suspension, crystalline forms, amorphous form, and drug combinations (Tecovirimat + cidofovir) and process for preparing Tecovirimat. The authors foresee the off-label use of Tecovirimat in the USA and Canada for MPX and other orthopoxvirus infections. The authors also trust that there is immense scope for developing new Tecovirimat-based treatments (new drug combinations with other antivirals) for orthopoxvirus and other viral diseases. Drug interaction studies and drug resistance studies on Tecovirimat are also recommended. Tecovirimat is believed to handle the current MPX outbreak and is a new hope of biosecurity against smallpox or orthopoxvirus-related bioterrorism attack.

Nanoplatform for the Delivery of Topotecan in the Cancer Milieu: An Appraisal of its Therapeutic Efficacy.

Chemotherapy has been the predominant treatment modality for cancer patients, but its overall performance is still modest. Difficulty in penetration of tumor tissues, a toxic profile in high doses, multidrug resistance in an array of tumor types, and the differential architecture of tumor cells as they grow are some of the bottlenecks associated with the clinical usage of chemotherapeutics. Recent advances in tumor biology understanding and the emergence of novel targeted drug delivery tools leveraging various nanosystems offer hope for developing effective cancer treatments. Topotecan is a topoisomerase I inhibitor that stabilizes the transient TOPO I-DNA cleavable complex, leading to single-stranded breaks in DNA. Due to its novel mechanism of action, TOPO is reported to be active against various carcinomas, namely small cell lung cancer, cervical cancer, breast cancer, and ovarian cancer. Issues of cross-resistance with numerous drugs, rapid conversion to its inactive form in biological systems, appended adverse effects, and higher water solubility limit its therapeutic efficacy in clinical settings. Topotecan nanoformulations offer several benefits for enhancing the therapeutic action of this significant class of chemotherapeutics. The likelihood that the target cancer cells will be exposed to the chemotherapeutic drug while in the drug-sensitive s-phase is increased due to the slow and sustained release of the chemotherapeutic, which could provide for a sustained duration of exposure of the target cancer cells to the bioavailable drug and result in the desired therapeutic outcome. This article explores nanoenabled active and passive targeting strategies and combinatorial therapy employing topotecan to ameliorate various cancers, along with a glimpse of the clinical studies utilizing the said molecule.

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).