Pegfilgrastim-Apgf (Nyvepria): Biosimilar USFDA Approval for the Treatment of Chemotherapy-induced Febrile Neutropenia and Current Updates on Clinical Trials.

Pegfilgrastim-apgf (nyvepria) was currently approved by FDA for the treatment of febrile neutropenia associated with non-myeloid malignancies receiving myelosuppressive anticancer drugs. It was developed by Pfizer, USA. It is a PEGylated leukocyte growth-stimulating factor indicated to reduce the incidence of febrile neutropenia in patients receiving anticancer drugs. Nyvepria is biosimilar to pegfilgrastim, approved by FDA on June 10, 2020. It is the fourth FDA-approved drug for the treatment of infection exhibiting febrile neutropenia. This review abridges the indicators in the development of nyvepria foremost to approval for the treatment of febrile neutropenia (FN), a biosimilar regulatory framework, and current updates on the clinical trials (CTs).

Clinical and epidemiological trends in childhood leprosy: A 20-year retrospective analysis from a tertiary care hospital in Jammu, North India.

Background Slightly more than half the total number of childhood leprosy cases worldwide are from India. Aim To analyze the clinical and epidemiological trends of childhood leprosy over 20 years in a tertiary care hospital. Methods We retrieved the medical records of all children less than 15 years of age registered in the leprosy clinic between April 1998 and March 2018. We tabulated and analyzed data pertaining to demographic details along with clinical findings such as cutaneous lesions, nerves involved, sensory loss, deformities, reactions, smear status, histopathology and treatment. Results Out of total 1548 leprosy cases registered during the study period, 55 (3.55%) cases of childhood leprosy were diagnosed. Thirty five (63.6%) children were in the age group of 11-15 years and 83.7% were migrants from other states. Thirteen (23.6%) children reported contact with a diagnosed case of leprosy, mainly in close contacts. Fifty three (96.4%) children presented with cutaneous lesions while 2 (3.6%) had pure neural involvement. Borderline tuberculoid leprosy was the most common clinical presentation in 27 (49.1%) followed by borderline lepromatous leprosy in 11 (18%). Thickened peripheral nerve trunks were detected in 42 (76.4%), most commonly the ulnar nerve. Reactional episodes occurred in 12 (21.8%) cases (Type 1 reaction, 10 (18.2%); Type 2 reaction, 2 (3.6%)). Grade 2 disability was detected in 4 (7.3%). Multidrug therapy was started in all patients, multibacillary (MB) regimen in 42 (76.3%) patients and paucibacillary (PB) regimen in 13 (23.7%). Twenty five (45.4%) children defaulted from the treatment. On comparing the data of 2008-18 with that of the previous decade (1998-2007), there was a higher proportion of migrant cases as compared to local cases (3:1-11:1) and MB cases as compared to PB cases (2:1-6:1). The proportion of treatment defaulters declined from 60% to 36%. Limitations Relapse rate could not be calculated due to inadequate follow-up period. As it is a hospital-based retrospective study with no active surveys, these findings may not reflect trends in the community. Conclusion Childhood leprosy continues to be a significant problem. There is a clear need to strengthen early detection, treatment and regular follow-up of these cases in both high and low endemic settings.

Nanotechnology-based Medicinal Products and Patents: A Promising Way to Treat Psoriasis

Psoriasis is an autoimmune skin disorder that is characterised by chronic inflammation and erythematous scaly patches. It has a significant impact on the patient's quality of life and can cause psychological stress. There are several aspects that cause psoriasis, for instance, environmental issues, immune disorders, bacterial infections, and genetic issues. Plentiful therapeutic means or treatments are accessible, but not any of them can completely and effectively cure psoriasis without hindering patient compliance. Hence, it becomes challenging to discover a new drug moiety or any drug delivery method to cure psoriasis. Conventional treatment of psoriasis involves anti-inflammatory agents, immune suppressants, phototherapy, and biological treatment, which were given in different forms such as topical, oral, or systemic formulations, but these all were unsuccessful to accomplish complete reduction of psoriasis as well as causing adverse side effects. In terms of dose frequency, doses, efficacy, and side effects, nanotechnology-based new formulations are the most promising prospects for addressing the challenges and limits associated with present psoriasis formulations. Hence, our major goal of this review is to present various advanced nanotechnological approaches for the effective topical treatment of psoriasis. In short, nano-formulations continue to be formed as very promising modalities in the treatment of psoriasis as they suggest improved penetration, targeted delivery, increased safety, and efficacy.

Inebilizumab-cdon: USFDA Approved for the Treatment of NMOSD (Neuromyelitis Optica Spectrum Disorder).

Inebilizumab-cdon (Uplizna™) was currently approved by the United States Food and Drug Administration (USFDA) for the treatment of NMOSD (neuromyelitis optica spectrum disorder). It was developed by Viela Bio (Nasdaq: VIE) USA. Inebilizumab-cdon (formerly MEDI-551) is a humanized antibody, which induces CD19 + B cell depletion by increasing antibody-dependent cell cytotoxicity (ADCC) and cell phagocytosis (ADCP) of effector cells. Various clinical trials exhibit its safe and effective pharmacokinetic and pharmacodynamic profile. In June 2019, Viela Bio submitted Biologics License Application (BLA) to the FDA based on the findings obtained from the N-Momentum trial. This article summarizes the milestones in the development of Inebilizumab-cdon leading to this approval for the treatment of advanced NMOSD.

Disseminated Histoplasmosis detected on peripheral blood smear examination in immunocompetent patients from non endemic region - Report of two cases from a tertiary care hospital.

Histoplasmosis is an opportunistic systemic infection caused by inhaling spores of a thermal dimorphic fungus Histoplasma capsulatum. Disseminated histoplasmosis is the most common form associated with acquired immune deficiency syndrome (AIDS). However, only a few cases of disseminated histoplasmosis are reported in immuno-competent hosts. Most infections in the immunocompetent hosts are asymptomatic or result in mild pulmonary disease. However the presence of Disseminated Histoplasmosis in immunocompetent host probably results due to prolonged exposure and delayed presentation We report two cases of progressive disseminated histoplasmosis in two immunocompetent patients from non-endemic region in Western Rajasthan, India. Also in both the cases, the first diagnosis was suggested by a peripheral blood smear, which is not a classical biological diagnostic method for fungal infection. Careful examination of Peripheral blood smear along with correct clinical history can aid in early diagnosis of disseminated histoplasmosis even in immunocompetent patients.

Self-Sorted, Random, and Block Supramolecular Copolymers via Sequence Controlled, Multicomponent Self-Assembly.

Multicomponent supramolecular copolymerization promises to construct complex nanostructures with emergent properties. However, even with two monomeric components, various possible outcomes such as self-sorted supramolecular homopolymers, a random (statistical) supramolecular copolymer, an alternate supramolecular copolymer, or a complex supramolecular block copolymer can occur, determined by their intermolecular interactions and monomer exchange dynamics and hence structural prediction is extremely challenging. Herein, we target this challenge and demonstrate unprecedented two-component sequence controlled supramolecular copolymerization by manipulating thermodynamic and kinetic routes in the pathway complexity of self-assembly of the constitutive monomers. Extensive molecular dynamics simulations provided useful mechanistic insights into the monomer exchange rates and free energy of interactions between the monomers that dictate the self-assembly pathway and sequence. The fluorescent nature of core-substituted naphthalene diimide monomers has been further utilized to characterize the three sequences via Structured Illumination Microscopy (SIM).

Hitherto unknown eight-connected frameworks formed from A4B4O12 metal organophosphate heterocubanes.

Modulation of a functional group on the distal part of a phosphate ester has been prudently exploited to selectively switch between the formation of D4R SBUs and 3-D framework structures. While amino substitution at the para-position of an aryl phosphate results in the isolation of tetra-amino functionalized discrete D4R zinc phosphate or its 4-connected 3-D framework, the introduction of an acetylamino substituent leads to a single-step assembly of a rare eight-connected 3-D framework solid.

Complex Structural Landscape of Titanium Organophosphonates: Isolation of Structurally Related Ti4, Ti5, and Ti6 Species and Mechanistic Insights.

[Ti(acac)2(OiPr)2] reacts with tert-butylphosphonic acid to yield a series of titanium organophosphonates such as tetranuclear [Ti4(acac)4(µ-O)2(µ-tBuPO3)2(µ-tBuPO3H)4]·2CH3CN (1), pentanuclear [Ti5(acac)5(µ-O)2(OiPr)(µ-tBuPO3)4(µ-tBuPO3H)2] (2), hexanuclear [Ti6(acac)6(µ-O)2(OiPr)2(µ-tBuPO3)6] (3), or [Ti6(acac)6(µ-O)3(OiPr)(µ-tBuPO3)5(µ-tBuPO3H)]·2CH3CN (4). The isolation of each of these products in pure form depends on the molar ratio of the reactants or the solvent medium. Among these, 3 is obtained as the only product when the reaction is conducted in CH2Cl2. The structural analysis reveals that a simple cluster growth route relates the clusters 1-4 to each other and that a reactive cyclic single-4-ring titanophosphonate [Ti(acac)(OiPr)2(tBuPO3H)]2 is the fundamental building block. While the tetranuclear 1 has structural resemblance to the D4R building block of zeolites, the hexanuclear clusters 3 and 4 have the shape of zeolitic D6R building blocks. The presence of adventitious water in the phosphonic acid (arising from small quantities of hydrogen-bonded water) results in the formation of µ-O2- bridges across an adjacent pair of titanium centers in clusters 1-4. To further verify the stability of the hexanuclear cluster over other structural forms, the reaction of tBuPO3H2 was performed with [Ti(acac)2(O)], instead of Ti(acac)2(OiPr)2, in CH3CN to yield [Ti6(acac)6(µ-O)4(µ-tBuPO3)4(µ-tBuPO3H)2]·2CH3CN (5). Compound 5 exhibits a core structure similar to those of 3 and 4 with small variations in the intracluster Ti-O-Ti linkage. Compound 3 is an efficient and selective catalyst for olefin epoxidation under both homogeneous and heterogeneous conditions.

Pentanuclear Lanthanide Mono-organophosphates: Synthesis, Structure, and Magnetism.

Research on rare-earth phosphates has recently received substantial interest because of their unique physical and chemical properties. In recent years, because of their low solubility, research interest has been built on developing methodologies to prepare nanostructures and grow single crystals of inorganic rare-earth phosphates. The chemistry of rare-earth organophosphates, however, is still at a latent stage. Contrary to the traditional hydrothermal route, we report rare examples of discrete pentanuclear lanthanide(III) organophosphate clusters assembled from a sterically encumbered monoester of phosphoric acid under mild reaction conditions. Single-crystal X-ray analysis revealed that all of the compounds possess a similar core structure, [Ln5(µ3-OH)(dipp)6(NO3)x(CH3OH)y(H2O)z]2+ [Ln = Nd (1), Sm (2), Eu (3), Gd (4), Tb (5), Dy (6), Ho (7), Er (8), Tm (9); dipp = 2,6-diisopropylphenylphosphate], where the anionic charge balance is maintained by the presence of chelating nitrate anions (in the case of 9, x = 0), protonated tmeda, or dipp2- ligands. The vacant coordination sites on the metal ions are satisfied by coordinated methanol or water molecules. The core structure of these clusters is built on a [Ln3(µ3-OH)(dipp)6] triangle where the phosphate ligands bridge to two further Ln(III) ions. The complexes display lanthanide contraction along the series, with Ln(III) ions displaying different coordination environments/geometries as we move along the series. All of the compounds have been characterized by both analytical and spectroscopic techniques. Magnetic studies revealed the presence of weak antiferromagnetic exchange through the bridging µ3-hydroxo moiety and organophosphate groups for the {GdIII5} analogue, with a significant magnetic entropy change (25.8 J kg-1 K-1, ΔH = 7 T). The anisotropic complexes reveal an absence of slow relaxation of magnetization, except for Nd (1), Dy (6), and Er (8), which show slow relaxation in an applied DC field.