Therapeutic Management of Chronic Lymphocytic Leukemia Presenting with Recurrent Massive Ascites

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy. Microscopic analysis and flow cytometry of the patient’s ascitic fluid were consistent with CLL, and he was treated with six cycles of obinutuzumab immunotherapy with the addition of acalabrutinib, resulting in near resolution of malignant ascites. A few cases have reported CLL manifesting as transudative or exudative ascites in elderly patients. A few previous cases have reported the development of ascites between 12 and 21 months after the initial treatment of CLL with chemotherapy. A unique feature of our patient is the presentation with malignant ascites nearly 7 years after the initial CLL treatment with chemotherapy. The intent of this case report is to bring awareness of ascites as a possible initial presenting symptom of CLL in patients with isolated abdominal distention with or without common clinical features of leukemia (i.e., splenomegaly, lymphadenopathy, and B-symptoms) and the therapeutic management thereafter. Malignant ascites may be associated with relapse or the transformation of leukemia; thus, prompt diagnosis and treatment should not be delayed.     

Fundamental understanding of the size and surface modification effects on r1, the relaxivity of Prussian blue nanocube@m-SiO2: a novel targeted chemo-photodynamic theranostic agent to treat colon cancer

A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. Herein, we have designed mesoporous silica (m-SiO₂)-coated Prussian blue nanocubes (PBNCs), functionalized with hyaluronic acid (HA) to construct a multifunctional PBNC@m-SiO₂@HA nanoplatform that exhibited good biocompatibility, excellent photodynamic activity, and in vitro T₁-weighted magnetic resonance imaging ability (r₁ ∼ 3.91 mM⁻¹ s⁻¹). After loading doxorubicin into the as-prepared PBNC@m-SiO₂@HA, the developed PBNC@m-SiO₂@HA@DOX displayed excellent pH-responsive drug release characteristics. Upon irradiation with 808 nm (1.0 W cm⁻²) laser light, PBNC@m-SiO₂@HA@DOX exhibited synergistic photodynamic and chemotherapeutic efficacy (∼78% in 20 minutes) for human colorectal carcinoma (HCT 116) cell line compared to solo photodynamic or chemotherapy. Herein, the chemo-photodynamic therapeutic process was found to follow the apoptotic pathway via ROS-mediated mitochondrion-dependent DNA damage with a very low cellular uptake of PBNC@m-SiO₂@HA@DOX for the human embryonic kidney (HEK 293) cell line, illustrating its safety. Hence, it may be stated that the developed nanoplatform can be a potential theranostic agent for future applications. Most interestingly, we have noted variation in r₁ at each step of the functionalization along with size variation that has been the first time modelled on the basis of the Solomon–Bloembergen–Morgan theory considering changes in the defect crystal structure, correlation time, water diffusion rate, etc., due to varied interactions between PBNC and water molecules.

A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer.     

Alternatives to rifampicin: A review and perspectives on the choice of strong CYP3A inducers for clinical drug–drug interaction studies

N‐Nitrosamine (NA) impurities are considered genotoxic and have gained attention due to the recall of several marketed drug products associated with higher‐than‐permitted limits of these impurities. Rifampicin is an index inducer of multiple cytochrome P450s (CYPs) including CYP2B6, 2C8, 2C9, 2C19, and 3A4/5 and an inhibitor of OATP1B transporters (single dose). Hence, rifampicin is used extensively in clinical studies to assess drug–drug interactions (DDIs). Despite NA impurities being reported in rifampicin and rifapentine above the acceptable limits, these critical anti‐infective drugs are available for therapeutic use considering their benefit–risk profile. Reports of NA impurities in rifampicin products have created uncertainty around using rifampicin in clinical DDI studies, especially in healthy volunteers. Hence, a systematic investigation through a literature search was performed to determine possible alternative index inducer(s) to rifampicin. The available strong CYP3A inducers were selected from the University of Washington DDI Database and their in vivo DDI potential assessed using the data from clinical DDI studies with sensitive CYP3A substrates. To propose potential alternative CYP3A inducers, factors including lack of genotoxic potential, adequate safety, feasibility of multiple dose administration to healthy volunteers, and robust in vivo evidence of induction of CYP3A were considered. Based on the qualifying criteria, carbamazepine, phenytoin, and lumacaftor were identified to be the most promising alternatives to rifampicin for conducting CYP3A induction DDI studies. Strengths and limitations of the proposed alternative CYP3A inducers, the magnitude of in vivo CYP3A induction, appropriate study designs for each alternative inducer, and future perspectives are presented in this paper.     

β-Cyclodextrin: a green supramolecular catalyst assisted eco-friendly one-pot three-component synthesis of biologically active substituted pyrrolidine-2-one

A green, novel and eco-efficient synthetic route towards the synthesis of highly substituted bio-active pyrrolidine-2-one derivatives was demonstrated using β-cyclodextrin, a water-soluble supramolecular solid as a green and eco-benign catalyst at room temperature under water–ethanol solvent medium. The exploration of the green catalyst β-cyclodextrin for the metal-free one-pot three-component synthesis of a wide range of highly functionalized bio-active heterocyclic pyrrolidine-2-one moieties from easily available aldehydes and amines explains the superiority and uniqueness of this protocol.

An eco-efficient protocol towards the synthesis of highly substituted bio-active pyrrolidine-2-one derivatives was demonstrated using β-cyclodextrin, a water-soluble supramolecular catalyst at room temperature under water–ethanol solvent medium.     

Knowledge,awareness and attitude of eye donation among non-clinical staff of a tertiary eye hospital in South India

Purpose:This study aimed to evaluate the knowledge, awareness and attitude of eye donation among non-clinical staff of tertiary eye hospitals and to convey a positive attitude toward eye donation by enhancing their awareness and knowledge.Methods:An online cross-sectional study was conducted among the non-clinical staff from all centers of a tertiary eye care hospital across Tamil Nadu. Quiz link was emailed to non-clinical staff of all the centers. On completion of the quiz, the participants viewed their respective scores and the correct answers to all questions. This activity was presumed to subsequently improve their knowledge and clear up the myths on eye donation.Results:Two hundred twenty-eight non-clinical staff from 11 hospitals participated in the quiz. Mean age was 35.3 ± 9.8 years and 130 were female staff (57.05%). One hundred eighty-one participants (79.39%) scored over 50% of the total 17 queries. One hundred eighty-six (81.58%) and 142 (62.28%) participants scored over 50% in the awareness section and knowledge section, respectively. Eye bank volunteers (73, 32.02%) were the main source of information. Twenty-four (10.53%) had already taken pledge for eye donation and 175 (76.75%) were willing to pledge, 29 (12.72%) were not willing to pledge. Twenty-two out of these 29 (75.86%) had no specific reason for not pledging. Family, religious reasons, lack of clarity and fear were least cited reasons (13.79%).Conclusion:Non-clinical staff of an eye hospital are easily approachable and are expected to be more knowledgeable by the general public around them. They might act as primary motivators in raising awareness within their family, friends, relatives and neighbors.     

Unexpected rapid rise of maternal serum anti-D levels during pregnancy.

Two cases are described where hydrops faetalis developed as a result of very sudden and unexpected rises in serum anti-D levels. In both cases intravascular intrauterine transfusion was employed and a favourable outcome obtained. These cases show that continued vigilance is required even when anti-D levels are low. Weak antibody titres may be detected using enzyme-treated red cells, and failure to use this more sensitive technique meant that in one of the cases the initial weak antibody was not detected. There is currently a debate about the use of this more sensitive test in view of the increased work involved.     

A unique experience with human pre-immune (12 weeks) and hypo-immune (16 weeks) fetal thymus transplant in a vascular subcutaneous axillary fold in patients with advanced cancer: a report of two cases.

BACKGROUND: The successful development of fetal cell/tissue transplantation in adults has resulted in the possibility of eventual therapeutic solutions with a variety of intractable diseases. Umbilical cord whole blood transplantation appears to be safe in the adult system. In severe forms of DiGeorge Syndrome, cultured thymus transplant can help in the reconstitution of the immune condition of the host. Successful fetal tissue transplant in adults has raised the hope of future effective gene transplant and its manipulation prospects to combat many diseases including hemopathies, inborn errors of metabolism, immunodeficiencies and even cancer and AIDS. MATERIALS AND METHOD: Two cases of advanced cancer were treated with fetal (pre-immune 12 weeks and hypo-immune 16 weeks) thymus transplants in subcutaneous vascular axillary folds, which were removed after one month. Thymuses were collected from consenting mothers undergoing hysterotomy and ligation. RESULTS AND ANALYSIS: Patient I was suffering from non-Hodgkins lymphoma (Ann Arbor Stage IV) and was receiving cyclophosphomide, doxorubicin, vincristine and prednisolone after a course of radiotherapy; she developed leucopenia (2.400/cmm), which improved after receiving a 16-week human fetal thymic graft. The leucopenia was eventually over-corrected and the leucocyte count reached 44,000/cmm within a month, which was reversed after the thymus was taken out. Histology of the excised thymic graft showed growth and proliferation without any graft vs. host (GVH) reaction. Patient 2 was suffering from breast duct carcinoma (T4, N2, M0,) with estrogen, progesterone, and epidermal growth factor negative status, and was treated with modified radical mastectomy and axillary clearance followed by chemotherapy with cyclophosphomide, methotrexate and 5-fluorouracil for six cycles. She also received a 12-week-old human fetal thymus at the contra-lateral axilla which was removed after one month. In this case the peripheral leucocyte count did not show appreciable variation as in the first case. However, histology of the excised thymic graft showed growth and proliferation with an appearance of Hassel's corpuscles. CONCLUSION: Pre-immune and hypo-immune human fetal thymic transplant is not rejected in patients suffering from advanced cancer within one month (observation period). Thymic lymphocyte shedding in the correction of leucopenia in the background of non-Hodgkin's lymphoma may have many therapeutic implications.