Formulation of Folate Receptor-Targeted Silibinin-Loaded Inhalable Chitosan Nanoparticles by the QbD Approach for Lung Cancer Targeted Delivery.

: Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. The main objective of this research was to develop folate receptor-targeted silibinin (SB)-loaded inhalable polymeric nanoparticles (FA-CS-SB-NPs) for the treatment of lung cancer. : The qbD approach was implemented to prepare SB-loaded nanoparticles.

Polymicrobial anaerobic sepsis due to Bacteroides fragilis, Eggerthella lenta, Ruminoccocus gnavus, and Bilophila wadsworthia in a patient with myeloproliferative neoplasm.

We report a rare case of polymicrobial anaerobic bacteremia caused by four different gut anaerobes: Bacteroides fragilis, Eggerthella lenta, Bilophila wadsworthia, and Ruminococcus gnavus. Early initiation of appropriate therapy and species identification with matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) resulted in full recovery from the infection. Our case highlights the clinical significance of polymicrobial cultures and the importance of performing anaerobic cultures for blood specimens to ensure proper identification and treatment.

RP-HPLC method development, validation and pharmacokinetic applicability in preclinical evaluation of rhein treated with novel diacerein eutectics.

The current study represents a bioanalytical method for the estimation of rhein (Rh, an active metabolite of diacerein, DIA) in rats treated with novel DIA eutectics to investigate the pharmacokinetics of DIA. A simple protein precipitation technique was used to extract Rh and the internal standard (IS), p-aminobenzoic acid, injected into a Phenomenex Gemini C column. The separation was achieved by a gradient elution comprising ammonium acetate (10 mm; pH 3.

Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant: SARS-CoV-2 Vaccine as a Potential Trigger.

Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are at a risk of developing immune-mediated tissue damage from activation of the donor's immunocompetent T cells by the recipient's normally expressed antigens, a phenomenon called graft-versus-host disease (GVHD). With the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), new vaccines have been developed to prevent morbidity and mortality, including the highly vulnerable hematologic malignancy patients after undergoing AHSCT. The early pathophysiologic events in GVHD include priming the donor T cells with molecules that are endogenous or pathogenic.

Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: In vitro and In vivo study.

Silibinin (SB) is shown to have an anticancer properties. However, its clinical therapeutic effects have been restricted due to its low water solubility and poor absorption after oral administration. The aim of this study was to develop SB-loaded PCL/Pluronic F68 nanoparticles for pulmonary delivery in the treatment of lung cancer.

T-cell prolymphocytic leukaemia associated with immune checkpoint inhibitor (pembrolizumab).

We describe the case of a man in his 60s with squamous cell carcinoma of the lung with brain metastasis treated with pembrolizumab who subsequently developed T-cell prolymphocytic leukaemia. He was transferred to our hospital with worsening dyspnoea, suspected hyperviscosity syndrome and tumour lysis syndrome. He was intubated and admitted to our critical care unit.

Serum sickness reaction to obinutuzumab in a patient with chronic lymphocytic leukaemia.

Serum sickness (SS) is a known phenomenon; however, it is commonly missed due to vague symptoms, and is usually confounded by other aetiologies that present similarly. Obinutuzumab is a novel anti-CD20 antibody agent that has been approved for chronic lymphocytic leukaemia (CLL) treatment. At the time of approval, it was not linked to SS; however, this phenomenon has been recognised with other anti-CD20 agents like rituximab.

Silibinin loaded inhalable solid lipid nanoparticles for lung targeting.

Aim: In the current study, efforts are being made to prepare Inhalable Silibinin loaded solid lipid nanoparticles (SLNs) with narrow size distribution with improved bioavailability.

Methods: SLNs were formulated by high shear homogenisation method SLNs were characterised, including Differential Scanning Calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR), particle size analysis, entrapment efficiency with Aerodynamic behaviour. The MTT assay was performed against A549 cell line, to measure their anticancer cell activity with study.

Application of a Validated RP-HPLC Method in Solubility and Dissolution Testing for Simultaneous Estimation of Diacerein and Its Active Metabolite Rhein in Presence of Coformers in the Eutectic Tablet Formulation.

The present study aimed to develop and validate a novel reversed-phase high-performance liquid chromatography method for simultaneous estimation of Diacerein (DIA) and Rhein (Rh, alkaline degradation product and active metabolite) in the presence of various coformers used to prepare eutectic oral formulation. Chromatographic separations were achieved on a Phenomenex Gemini C18 column (250 mm × 4.6 mm, 5 μm) placed in the thermostated column oven at 40°C.

Congenital dysfibrinogenaemia presented with preterm premature rupture of the membranes and vaginal bleeding.

A 26-year-old woman was found to have congenital dysfibrinogenaemia after presenting to our hospital with premature rupture of the membranes and vaginal bleeding. Given the absence of clear guidelines for the management of pregnancy complicated by dysfibrinogenaemia, we followed expert consensus that exists among published works, with some modifications. This case was managed by a multidisciplinary team of obstetrics-gynaecology, haematology and paediatric haematology.

Concurrent Diagnosis of Acute Myeloid Leukemia and COVID-19: A Management Challenge.

The emergence of coronavirus disease 2019 (COVID-19) has created new challenges in the management of serious diseases. We describe a 41-year-old male who presented with fever, watery diarrhea, and epistaxis. Initial workup revealed pancytopenia with >50% blasts on the peripheral smear raising suspicion of acute myeloid leukemia (AML) (later confirmed by bone marrow biopsy as AML with myelodysplasia-related changes) and a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Intractable hypercalcemia in a patient with multiple myeloma: An infectious etiology.

Hypercalcemia is a common laboratory finding in patients with malignancy, as well as with granulomatous disease. We report the case of a 75-year-old man with multiple myeloma (MM) who presented with generalized weakness, fever, and intractable hypercalcemia. The hypercalcemia proved difficult to treat despite well-controlled MM, as well as adequate use of bisphosphonates and calcitonin.

HTLV-positive adult T-cell leukaemia/lymphoma with Epstein-Barr virus and hepatitis B coinfection.

Human T-cell lymphotropic virus (HTLV) is a human oncoretrovirus known to cause adult T-cell leukaemia/lymphoma (ATLL). Coinfection of human T-lymphotropic virus type 1 with Epstein-Barr virus (EBV) results in enhanced expression of the HTLV virus and leads to aggressive organ involvement from T-cell malignancy. It has also been observed that the prevalence of hepatitis B infection has been higher in patients with HTLV ATLL as compared with the general population in certain countries.

Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare haematological malignancy defined by concurrent expression of CD4, CD56, BCL-2 and CD123. The disease has a very poor prognosis and there are no well-established treatment guidelines. We describe a case of BPDCN in a 65-year-old female patient with myeloproliferative disorder (essential thrombocythemia) and chronic lymphocytic leukaemia.

Spontaneous Subdural Hematoma in Patient with Polycythemia Vera.

Background: Polycythemia vera (PV) is a myeloproliferative disorder usually characterized by an increase tendency toward thromboembolic events. Spontaneous hemorrhage/bleeding in PV patients is seldom reported in neurosurgical literature.

Case Description: We report the case of a 76-year-old male with PV who developed a spontaneous subdural hematoma requiring surgical evacuation.

An unusual presentation of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a B-cell lymphocytic neoplasm with indolent clinical course. If identified early, observation is opted. Many variables lead to the initiation of treatment.

Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability.

A novel cationic nanoemulsified in-situ ophthalmic gel of loteprednol etabonate (LE) was developed to improve the permeability and retention time of formulations for overall improvement of drug's ocular bioavability. Capryol 90 (oil phase), tween 80 (surfactant) and transcutol P (cosurfactant) was selected as formulation excipients to construct pseudoternary phase diagrams and nanoemulsion region was recognized from diagrams. Spontaneous emulsification method was used to manufacture LE nanoemulsion and it was optimized using 3 factorial design by considering the amount of oil and the ratio of surfactant to cosurfactant (S) as independent variables and evaluated for various physicochemical properties.

Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors.

Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma.

Dissolution enhancement of chlorzoxazone using cogrinding technique.

Purpose: The aim of the present work was to improve rate of dissolution and processing parameters of BCS class II drug, chlorzoxazone using cogrinding technique in the presence of different excipients as a carrier.

Materials And Methods: The drug was coground with various carriers like polyethylene glycol (PEG 4000), hydroxypropyl methylcellulose (HPMC) E50LV, polyvinylpyrrolidone (PVP)K30, Kaolin and Neusilin US2 using ball mill, where only PEG 4000 improved dissolution rate of drug by bringing amorphization in 1:3 ratio. The coground mixture after 3 and 6 h was evaluated for various analytical, physicochemical and mechanical parameters.

Yttrium-90 radioembolization of hepatic metastases from colorectal cancer.

Liver metastases from colorectal cancer (CRC) result in substantial morbidity and mortality. The primary treatment is systemic chemotherapy, and in selected patients, surgical resection; however, for patients who are not surgical candidates and/or fail systemic chemotherapy, liver-directed therapies are increasingly being utilized. Yttrium-90 (Y-90) microsphere therapy, also known as selective internal radiation therapy (SIRT) or radioembolization, has proven to be effective in terms of extending time to progression of disease and also providing survival benefit.

Urinary concentrations of ADAM 12 from breast cancer patients pre- and post-surgery vs. cancer-free controls: a clinical study for biomarker validation.

Background: The ADAMs (A Disintegrin and Metalloproteinases) are a family of multi-domain, zinc-dependent metalloproteinase enzymes. ADAM 12 has been previously associated with the onset and progression of breast cancer, and elevated levels of ADAM 12 have been previously found in the urine of breast cancer patients. Aims of the current study are: 1) establish the viability of urinary ADAM 12 as a diagnostic marker for breast cancer, and 2) explore the effects of surgical tumor removal on the levels of urinary ADAM 12.

Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery.

Introduction: The aim of present work was to develop intestinal-targeted pellets of Budesonide, a potent glucocorticoid, used for the treatment of ulcerative colitis and Crohn's disease by extrusion and spheronization method. Current available oral formulations of Budesonide have low efficacy because of the premature drug release in the upper part of the gastrointestinal tract. In this study, a pH-controlled intestinal-targeted pellet of budesonide was established using 3(2) full factorial design by giving an enteric coating with Eudragit S100.

Quality by design approach for oral bioavailability enhancement of irbesartan by self-nanoemulsifying tablets.

The present investigation was aimed to develop self-nanoemulsifying tablets (SNETs) as novel nanosized solid oral dosage forms for Irbesartan (IRB). In the first part of the investigation, IRB-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were developed using Capryol 90 - Cremophor RH40 - Transcutol P as three component (oil - surfactant - cosurfactant) SNEDDS system. On the basis of ternary phase diagram IRB-loaded SNEDDS were optimized by using Design of Experiments (DoE) and Principal component analysis (PCA) with amount of oil and surfactant: cosurfactant ratio (Km) as factors.

Influence of excipients and processing conditions on the development of agglomerates of racecadotril by crystallo-co-agglomeration.

Purpose: The purpose of the present investigation was to improve the flow and mechanical properties of racecadotril by a crystallo-co-agglomeration (CCA) technique. Direct tableting is a requirement of pharmaceutical industries. Poor mechanical properties of crystalline drug particles require wet granulation which is uneconomical, laborious, and tedious.