Giant cell interstitial pneumonia: an unusual finding in a case of preoperative death.

Giant cell interstitial pneumonia (GIP) is an exceedingly rare, debatable, perplexing, occupational lung disease, which most commonly affects individuals exposed to hard metal dust. We report a case of GIP in a 60-year-old man, scheduled for coronary artery bypass graft surgery and died during induction of general anesthesia despite all efforts to resuscitate him. Patient's relatives lodged complaint with the police alleging the negligence by the attending physicians. Despite inaccessible data pertaining to the occupation, clinical history, and radiographic findings, the diagnosis was GIP due to the presence of intra-alveolar, bizarre, "cannibalistic" multinucleated giant cells-the histologic sine qua non of GIP. To the best of our knowledge, this is the first case report of GIP in the world literature that was diagnosed on histopathologic examination of lung tissue obtained at medicolegal autopsy.

Accurate prostate cancer detection based on enrichment and characterization of prostate cancer specific circulating tumor cells.

BACKGROUND: The low specificity of serum PSA resulting in the inability to effectively differentiate prostate cancer from benign prostate conditions is a persistent clinical challenge. The low sensitivity of serum PSA results in false negatives and can miss high-grade prostate cancers. We describe a non-invasive test for detection of prostate cancer based on functional enrichment of prostate adenocarcinoma associated circulating tumor cells (PrAD-CTCs) from blood samples followed by their identification by immunostaining for pan-cytokeratins (PanCK), prostate specific membrane antigen (PSMA), alpha methyl-acyl coenzyme-A racemase (AMACR), epithelial cell adhesion molecule (EpCAM), and common leucocyte antigen (CD45). METHODS: Analytical validation studies were performed to establish the performance characteristics of the test using VCaP prostate cancer cells spiked into healthy donor blood (HDB). The clinical performance characteristics of the test were evaluated in a case-control study with 160 known prostate cancer cases and 800 healthy males, followed by a prospective clinical study of 210 suspected cases of prostate cancer. RESULTS: Analytical validation established analyte stability as well as acceptable performance characteristics. The test showed 100% specificity and 100% sensitivity to differentiate prostate cancer cases from healthy individuals in the case control study and 91.2% sensitivity and 100% specificity to differentiate prostate cancers from benign prostate conditions in the prospective clinical study. CONCLUSIONS: The test accurately detects PrAD-CTCs with high sensitivity and specificity irrespective of stage, serum PSA or Gleason score, which translates into low risks of false negatives or overdiagnosis. The high accuracy of the test could offer advantages over PSA based prostate cancer detection.

Amniotic fluid embolism: a cause of sudden maternal death and police inquest.

Amniotic fluid embolism (AFE) is a rare, unforeseeable, unpreventable, and dreadful complication of pregnancy. Histological diagnosis is still the criterion standard for its detection because of the lack of any reliable clinical laboratory tests. The diagnosis of AFE has a close association with medicolegal aspects of obstetric death. Amniotic fluid embolism occurs when massive amount of amniotic fluid abnormally enters the maternal venous system. We report a case of a 33-year-old healthy woman (G2, P2, L1) admitted to a private nursing care hospital with 37 weeks gestation for delivery. She normally delivered a healthy 2.8-kg infant boy. After 15 minutes of delivery, she developed tonic-clonic seizures, breathlessness, and loss of consciousness and died within 4 hours after onset of symptoms. The sudden death of a healthy mother led to medical negligence claim by the relatives, and a police case was filed against the private nursing care obstetrician. Despite a brief clinical history, meticulous microscopic examination of lungs revealed pulmonary microvasculature filled with fetal squamous cells, hair, and mucin. The final cause of sudden maternal death was given as AFE and pulmonary edema. This report highlights the importance of detailed microscopic examination of lungs and the need to study as many histopathologic sections as possible to rule out this entity.

X-ray computed microtomography datasets for osteogenic nanofibrous coated titanium implants.

Surface modifications of titanium implant influences the quality of osseointegration and are associated with favourable treatment prognosis in orthopaedic and cranio-maxillofacial cases. Hence, unlike previous works, the peri-implant region details of our novel osteogenic nanofibrous coated implants placed in rabbits (n = 6 + 1) were recorded over a 12-week period using a micro-CT imaging system. In this unique contribution, we have created a computed tomography (CT) library of rabbit's tibiae anatomy with osteogenic nanofibrous coated/uncoated implants and are introductory useful assets for investigating the correlation between osteogenic nanofibers coated implants and its effect on improved osseointegration. Apart from using this CT dataset to conduct serial 2D image studies, three-dimensional (3D) reconstructions, assessing segmentation algorithms and developing adequate image quantitation tools, there may be positive applications of these in comparative investigations of similar or related preclinical as well as future clinical studies, further design planning, development etc. required for evolution of implants beyond the present state of art.

Circulating tumor cell assay to non-invasively evaluate PD-L1 and other therapeutic targets in multiple cancers.

Biomarker directed selection of targeted anti-neoplastic agents such as immune checkpoint inhibitors, small molecule inhibitors and monoclonal antibodies form an important aspect of cancer treatment. Immunohistochemistry (IHC) analysis of the tumor tissue is the method of choice to evaluate the presence of these biomarkers. However, a significant barrier to biomarker testing on tissue is the availability of an adequate amount of tissue and need for repetitive sampling due to tumor evolution. Also, tumor tissue testing is not immune to inter- and intra-tumor heterogeneity. We describe the analytical and clinical validation of a Circulating Tumor Cell (CTC) assay to accurately assess the presence of PD-L1 22C3 and PD-L1 28.8, ER, PR and HER2, from patients with solid tumors to guide the choice of suitable targeted therapies. Analytically, the test has high sensitivity, specificity, linearity and precision. Based on a blinded case control study, the clinical sensitivity and specificity for PD-L1 (22C3 and 28.8) was determined to be 90% and 100% respectively. The clinical sensitivity and specificity was 83% and 89% for ER; 80% and 94% for PR; 63% and 89% for HER2 (by ICC); and 100% and 92% for HER2 (by FISH), respectively. The performance characteristics of the test support its suitability and adaptability for routine clinical use.

Albumin Based Iohexol Nanoparticles for Computed Tomography: An In Vivo Study.

Iohexol is a commonly used second generation non-ionic iodinated contrast agent with a multitude of advantages such as low osmolarity and competent intravenous countenance having minimum adverse reactions. Our study anticipated to improve the efficacy of Iohexol as a contrast enhancing agent for Computed Tomography, by envisaging bio-compatible albumin based Iohexol nanoparticles. This nanoparticulate system was developed primarily to enhance the anatomic imaging while increasing its residence time in the blood pool. Towards this goal, we developed Iohexol albumin nanoparticles using glutaraldehyde as a cross linking agent, and Polyethylene glyocol Iohexol albumin nanoparticles by physical adsorption to ameliorate its circulation time. These formulations were studied in comparison to the clinically available Iopamidol™. Both Iohexol albumin nanoparticles and Polyethylene glyocol Iohexol albumin nanoparticles were characterized for its size, physicochemical properties and entrapment efficiency. Iohexol albumin nanoparticles showed a size range of 254±5 nm and post surface modification the size of Polyethylene glyocol Iohexol albumin nanoparticles was found to be 283±7 nm in diameter, with and entrapment efficiency Iohexol as of 85%. Further, In vivo computed tomography imaging in New Zealand white rabbits for the developed formulations manifested an enhancement in the anatomical structures of heart, liver and kidneys along with an increased residence time in the blood pool of 3 h in contrast to Iopamidol™. Our study interprets that Polyethylene glyocol Iohexol albumin nanoparticles have prolonged residence time producing much greater conspicuity of anatomic features and warrants further detail study of the formulation in disease models.

Accentuated osseointegration in osteogenic nanofibrous coated titanium implants.

Anchoring of endosseous implant through osseointegration continues to be an important clinical need. Here, we describe the development of superior endosseous implant demonstrating enhance osseointegration, achieved through surface modification via coating of osteogenic nanofibres. The randomized bio-composite osteogenic nanofibres incorporating polycaprolactone, gelatin, hydroxyapatite, dexamethasone, beta-glycerophosphate and ascorbic acid were electrospun on titanium implants mimicking bone extracellular matrix and subsequently induced osteogenesis by targeting undifferentiated mesenchymal stem cells present in the peri-implant niche to regenerate osseous tissue. In proof-of-concept experiment on rabbit study models (n = 6), micro-computed tomography (Micro-CT), histomorphometric analysis and biomechanical testing in relation to our novel osteogenic nanofibrous coated implants showed improved results when compared to uncoated controls. Further, no pathological changes were detected during gross examination and necropsy on peri-implant osseous tissues regenerated in response to such coated implants. The findings of the present study confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and favours the dynamics of osseointegration.

Osteogenic Nanofibrous Coated Titanium Implant Results in Enhanced Osseointegration: In Vivo Preliminary Study in a Rabbit Model.

A titanium implant surface when coated with biodegradable, highly porous, osteogenic nanofibrous coating has shown enhanced intrinsic osteoinductive and osteoconductive properties. This coating mimics extracellular matrix resulting in differentiation of stem cells present in the peri-implant niche to osteoblast and hence results in enhanced osseointegration of the implant. The osteogenic nanofibrous coating (ONFC) consists of poly-caprolactone, gelatin, nano-sized hydroxyapatite, dexamethasone, ascorbic acid and beta-glycerophosphate. ONFC exhibits optimum mechanical properties to support mesenchymal stem cells and steer their osteogenic differentiation. ONFC was subjected to various characterization tests like scanning electron microscopy, Fourier-transform infrared spectroscopy, x-ray diffractometry, thermal degradation, biomineralization, mechanical properties, wettability and proliferation assay. In pre-clinical animal trials, the coated implant showed enhanced new bone formation when placed in the tibia of rabbit. This novel approach toward implant bone integration holds significant promise for its easy and economical coating thus marking the beginning of new era of electrospun osteogenic nanofibrous coated bone implants.