PD-L1 expression in muscle invasive urothelial carcinoma: Comparison of SP142 and SP263 assay

Introduction: High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC). Methods: We evaluated Ventana PD-L1 “SP263 and SP142” qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis. Results: SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node. Conclusion: PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.

Heterotopic pregnancy with spontaneous intrauterine conception: a rare clinical entity with diagnostic dilemma.

Twenty-one years old primigravida presented to emergency with amenorrhoea for 2 months and complaints of severe abdominal pain for few hours. The pain was associated with 2 episodes of fainting attacks in emergency during the period of observation. Viable intrauterine pregnancy of 8-9 weeks along with collection of fluid in the Pouch of Douglas was detected by ultrasound examination and on laparotomy ectopic pregnancy was confirmed with haemoperitoneum of 2 litres with 500gms of clots. Histopathology report confirmed the tubal ectopic pregnancy and postlaparotomy, transvaginal sonography confirmed the salvage of the intrauterine pregnancy. Despite massive haemoperitoneum, the pregnancy continued till 40+6 weeks with uneventful antenatal period. She underwent emergency caesarean section for meconium stained liquor with foetal distress and delivered of an alive healthy female of 2.5 kg with good Apgar score.

Somatic embryogenesis and plant regeneration from immature embryo explant of papaya (Carica papaya L. cv. washington and honey dew).

Immature zygotic embryo explants of Carica papaya were cultured on MS medium supplemented with 2,4-D (2.0 mg/l) and formed globular embryos on explants without callus formation in 4-6 weeks. Maturation and conversion of somatic embryos was also achieved on the same medium. Cotyledonary stage embryos germinated to 63.66 and 68.33% in cv. honey dew and washington respectively in MS basal medium supplemented ABA (0.5 microm/l). Robust development and proliferation of plantlet roots in vitro was obtained on MS basal medium. Hardened plantlets have 60% survival rate.

Non-antimicrobial properties of tetracyclines - dental and medical implications

The tetracyclines are a group of broad-spectrum antimicrobial agents. The first of these compounds, chlortetracycline was isolated from Streptomyces aureofaciens by Benjamin Duggar and introduced into the market in 1948. In 1952, tetracycline was derived semisynthetically from chlortetracycline by removal of its chlorine atom by catalytic hydrogenation. Methacycline, doxycycline and minocycline are all semi-synthetic derivatives. The tetracyclines are closely congeneric derivatives of the polycyclic napthacenecarboxamide. The tetracyclines possess a wide range of antimicrobial activity against gram-positive and gram-negative bacteria. In vitro, these drugs are primarily bacteriostatic. Tetracyclines have been used extensively as antimicrobial agents for the treatment of various types of periodontal diseases until light was shed on their equally important non-antimicrobial properties by Golub. The tetracyclines and their non-antimicrobial, chemically modified analogues have properties that appear to modulate host response by inhibiting the activity of the matrix metalloproteinases that cause collagen destruction. They also inhibit osteoclast function, stimulate osteoblastic bone formation, and regulate angiogenesis.

Intraoral botryomycosis masquerading as a pyogenic granuloma.

Bacterial pseudomycosis also known as Botryomycosis is a rare, indolent infection that has been described in patients with immunodeficiency and tissue with decreased healing ability. It affects the visceral organs and infection in the head and neck has been described as affecting the tongue and jaw bones. Histologically, the disease is characterized by the presence of 'Bollinger granules', surrounded by neutrophils in a fibrocellular stroma. A case of gingival Botryomycosis is presented which was diagnosed as a routine pyogenic granuloma in a healthy male.

Serological study of Japanese encephalitis in Nepal.

Antibodies against Japanese encephalitis virus (JEV) were examined in 356 serum samples from individuals visiting Tribhuvan University Teaching Hospital using neutralization test. A total of 13.2% (47/356) seropositivity was observed. Antibody positivity against both Nakayama-NIH and Beijing-1 strains was seen in 7.9% subjects. Infection by Nakayama-NIH strain alone was seen to be 4.2% while 1.1% of study populations were found to be infected only by Beijing-1 strain. High antibody titer was observed in the 20-40 years age-group and did not increase with age. Seropositivity was more common in zone-A (Tarai) area compared to zone-B (Hills) and zone-C (Mountains). Spectrum of antigenicity of JEV in zone-A as shown by neutralization test was identical to Indian isolates (strains). Difference in seropositivity was observed against Nakayama-NIH and Beijing-1 strain in zone-B and C indicating recent spread of JEV in these areas.

Organ fluid compartments in rats exposed to high altitude.

Rats were exposed to acute hypobaric hypoxia corresponding to an altitude of 6,100 m for 5 hours and 24 hours and were studied for organ fluid changes. Total water and extracellular water content of various organs, i.e. lung, liver, spleen, heart, kidney, muscle, brain testis and subcutaneous tissue were determined by the difference of dry and wet weights and using radiobromide-82 respectively. Lung and liver were found to be significantly hydrated with lower water contents in subcutaneous tissue, spleen and muscle on prolonged exposure. The data indicated a shift of fluids from extracellular to intracellular compartment.