Correlation of Programmed Death-Ligand 1 Expression With Lung Adenocarcinoma Histologic and Molecular Subgroups in Primary and Metastatic Sites.

Programmed death-ligand 1 (PD-L1) expression in terms of the tumor proportion score (TPS) is the main predictive biomarker approved for immunotherapy against lung nonsmall cell carcinoma. Although some studies have explored the associations between histology and PD-L1 expression in pulmonary adenocarcinoma, they have been limited in sample size and/or extent of examined histologic variables, which may have resulted in conflicting information. In this observational retrospective study, we identified primary and metastatic lung adenocarcinoma cases in the span of 5 years and tabulated the detailed histopathologic features, including pathological stage, tumor growth pattern, tumor grade, lymphovascular and pleural invasion, molecular alterations, and the associated PD-L1 expression for each case. Statistical analyses were performed to detect associations between PD-L1 and these features. Among 1658 cases, 643 were primary tumor resections, 751 were primary tumor biopsies, and 264 were metastatic site biopsies or resections. Higher TPS significantly correlated with high-grade growth patterns, grade 3 tumors, higher T and N stage, presence of lymphovascular invasion, and presence of MET and TP53 alterations, whereas lower TPS correlated with lower-grade tumors and presence of EGFR alterations. There was no difference in PD-L1 expression in matched primary and metastases, although higher TPS was observed in metastatic tumors due to the presence of high-grade patterns in these specimens. TPS showed a strong association with a histologic pattern. Higher-grade tumors had higher TPS, which is also associated with more aggressive histologic features. Tumor grade should be kept in mind when selecting cases and blocks for PD-L1 testing.

Native mitral valve staphylococcus endocarditis with a very unusual complication: Ruptured posterior mitral valve leaflet aneurysm.

Infective endocarditis (IE) is a life-threatening disease associated with in-hospital mortality of nearly one in five cases. IE can destroy valvular tissue, which may rarely progress to aneurysm formation, most commonly at the anterior leaflet in instances of mitral valve involvement. We present a remarkable case of a patient with IE and a rare complication of a ruptured aneurysm of the posterior leaflet of the mitral valve. Two- and Three-dimensional transesophageal echocardiography, intra-operative videography, and histopathologic analysis revealed disruption at this unusual location-at the junction of the P2 and P3 scallops, surrounded by an annular abscess.

Performance of Abbott ID Now COVID-19 Rapid Nucleic Acid Amplification Test Using Nasopharyngeal Swabs Transported in Viral Transport Media and Dry Nasal Swabs in a New York City Academic Institution.

The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real-time reverse transcription-PCR (RT-PCR) platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. The two platforms demonstrate comparable performances; however, the run times for each assay are 3.5 h and 45 min, respectively. In search for a platform with a shorter turnaround time, we sought to evaluate the recently released Abbott ID Now COVID-19 assay, which is capable of producing positive results in as little as 5 min. We present here the results of comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID Now. Regardless of method of collection and sample type, Abbott ID Now COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.

Environmental arsenic toxicity in West Bengal, India: A brief policy review.

High-level arsenic contamination of drinking water in West Bengal (WB), India is a grave public health concern, with 26 million people remaining affected. Two decades of research has provided detailed information on multiple aspects of exposure assessment and risk characterization. However, policy paralysis due to lack of finances and lack of any administrative coordination between the Central and State Governments has hampered the implementation of long-term solutions. Household- and community-level arsenic removal units have provided some relief to the suffering population. In view of the increased funding through the 12th Five-Year Plan period, it is the responsibility of the authorities to implement piped water supply schemes with single-point treatment facilities as the permanent solution to this three-decade-long crisis. Incorporating research evidence into policy and focusing on behavior change communication would be crucial to that end.

Validation of PD-L1 clone 22C3 immunohistochemical stain on two Ventana DISCOVERY autostainer models: detailed protocols, test performance characteristics, and interobserver reliability analyses.

Immunohistochemical (IHC) stain for PD-L1 as a biomarker for immunotherapy is recommended in non-small cell lung cancer (NSCLC). Under the FDA, the selection of patients for pembrolizumab requires companion diagnostic testing using the Dako Agilent PD-L1 IHC 22C3 pharmDx kit performed on the Dako Autostainer Link 48 platform. However, because it is not widely available, there is need for cross-platform validation. Existing studies provide incomplete protocol detail. In our study, 73 lung tumors were stained using the FDA-approved test ('gold standard'). The same blocks were stained using two different models of the Ventana DISCOVERY platform (ULTRA, n = 73 and XT, n = 70) using different parameters, and interpreted by three pathologists. The ULTRA group met College of American Pathologists (CAP) validation criteria (concordance 91.8%) while the XT group did not (concordance 67.1%). Using tumor proportion score (TPS) ≥1% and TPS ≥50% as cut-offs, the ULTRA protocol had higher sensitivity (97.8% and 91.7%) than XT (73.3% and 60.9%) and similar specificity (ULTRA 88.9% and 100%, XT 88% and 100%). Discordance between ULTRA and XT was 27%, and in all these cases ULTRA was concordant with gold standard. Interobserver reliability was substantial for ULTRA and almost perfect for XT, providing evidence that staining rather than observer variability accounts for XT's inferior performance. Cross-validation of the clinically used 22C3 anti PD-L1 antibody test with substantial interobserver agreement is possible on the commonly used the Ventana DISCOVERY ULTRA automated instrument, while the validation failed on the XT. Cautious attention to detail must be paid when choosing cross-validation parameters.

Association of SARS-CoV-2 genomic load trends with clinical status in COVID-19: A retrospective analysis from an academic hospital center in New York City.

The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2, as reflected by the Cycle threshold (Ct) value of the RT-PCR, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients' clinical status. Among 457 patients with COVID-19 pneumonia between 3/31/2020-4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2-3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p<0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms. Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia.

First Report of Bilateral External Auditory Canal Cochlin Aggregates ("Cochlinomas") with Multifocal Amyloid-Like Deposits, Associated with Sensorineural Hearing Loss and a Novel Genetic Variant in COCH Encoding Cochlin.

Pathogenic variants in COCH, encoding cochlin, cause DFNA9 deafness disorder with characteristic histopathologic findings of cochlin deposits in the inner and middle ears. Here, we present the first case of deafness associated with bilateral external auditory canal (EAC) cochlin deposits, previously unreported evidence suggestive of cochlin-derived amyloid formation, and a novel COCH variant. A 54-year-old woman presented with progressive sensorineural hearing loss and bilateral EAC narrowing by subcutaneous thickening. Excision and histologic evaluation of tissue from both EACs showed paucicellular eosinophilic aggregates containing multiple Congo red-positive foci with yellow and green birefringence under crossed polarization light microscopy. Mass spectrometry performed on both the Congo red-positive and Congo red-negative areas identified cochlin as the most abundant protein, as well as a low abundance of universal amyloid signature peptides only in the Congo red-positive areas. Peptides indicative of a canonical amyloid type were not detected. Electron microscopy showed haphazard, branched microfibrils (3-7 nm in diameter) consistent with cochlin, as well as swirling fibrils (10-24 nm in diameter) reminiscent of amyloid fibrils. Cochlin immunohistochemical staining showed positivity throughout the aggregates. Sequencing of the entire COCH gene coding region from the patient's blood revealed a novel variant resulting in a non-conservative amino acid substitution of isoleucine to phenylalanine (c.1621A>T, p.I541F) in the vWFA2 domain at the protein's C-terminus. Our findings reveal a new pathologic manifestation of cochlin, raise the possibility of previously undescribed cochlin-derived amyloid formation, and highlight the importance of thoroughly investigating all aggregative tissue findings in the practice of diagnostic pathology.

Sarcomatoid carcinoma in cytology: Report of a rare entity presenting in pleural and pericardial fluid preparations.

Sarcomatoid carcinoma is rarely found in pleural or pericardial fluid, with very few cases published to date. Here, we describe a 59-year-old female who presented with cough persisting for 5 months. Chest CT scan revealed a 6.0 cm cavitary mass in the left lung base with bulky mediastinal and hilar lymphadenopathy. An additional 1.2 cm right adrenal mass was seen and was suspicious for metastatic disease. The patient developed dyspnea, tachycardia, pleuritic chest pain and generalized weakness and was admitted to the hospital. She was found to have pleural and pericardial effusions, which were drained and sent to cytology. The fluid revealed enlarged highly pleomorphic malignant cells, some displaying multinucleation with irregular nuclear borders, coarse chromatin and prominent nucleoli. Tumor cells were positive for CK7 and Vimentin and negative for MOC-31, Ber-EP4, B72.3, Sox10, Melan-A, TTF-1, Napsin-A and CK20. A concurrent surgical biopsy of the tumor mass displayed immunopositivity for AE1/AE3 and CAM5.2. The tumor was negative for p40, TTF-1, calretinin, D2-40 and STAT6. A diagnosis of sarcomatoid carcinoma with giant cells and spindle cells was rendered. Sarcomatoid carcinomas of the lung are very uncommon consisting of 1% of non-small-cell lung carcinomas and are even more unusual in cytology specimens. Despite its rarity, it is important to keep this entity in mind in the differential diagnosis of a fluid specimen with bizarre nuclear atypia and the above staining pattern.

Papillary thyroid carcinoma metastatic to the pancreas: Case report.

Papillary thyroid carcinoma (PTC) is generally associated with an excellent long-term outcome. Distant metastasis is rare with only 5-7% of patients developing distant disease. Metastasis of PTC to the pancreas is an exceedingly rare occurrence. To date, few cases have been reported. We present the case of an 81-year-old man with past medical history of PTC status post total thyroidectomy with local recurrence treated with radioactive iodine and selective neck dissection. Ten years after his initial diagnosis, PET-CT scan revealed a new hypermetabolic 1.1 cm × 0.9 cm left lower lobe lung nodule and hypermetabolism in the proximal body of the pancreas. Follow-up MRI cholangiogram showed a 1.0 × 0.8 cm T1 hypointense lesion in the proximal body of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreatic mass showed neoplastic epithelial cells arranged in papillary clusters with fibrovascular cores and syncytial sheets with high nuclear to cytoplasmic ratio, visible nucleoli, nuclear pallor, focal nuclear grooves, and rare intranuclear pseudoinclusions. Immunohistochemical stains performed on the smears showed positive nuclear expression of TTF-1 and PAX-8. The findings were consistent with metastatic PTC. Surgical resection of the lung nodule confirmed metastatic PTC. Pancreatic metastases usually occur after long time intervals with reports of up to 8 years in PTC. This makes the diagnosis more challenging, and metastatic disease should always be in the differential diagnosis in cases presenting with a pancreatic mass, especially in patients with a prior malignancy.

Studying Policy Changes in Disaster Management in India: A Tale of Two Cyclones.

OBJECTIVE: The mainstay of India's disaster management policy until the early 2000s had been relief and rescue operations. The Odisha Super Cyclone (1999) with 10,000 deaths and US $3 billion economic damage provided a rude awakening. Recognizing the importance of preemptive preparedness, the government initiated systematic steps to implement a national framework interlinking economic, environmental, and overall developmental issues for efficient response to and mitigation of disasters. METHODS: We attempted a critical analysis of this paradigm shift in India's disaster management policy through the prism of 2 cyclones, 14 years apart in time. RESULTS: With improved preparedness and response measures, the death toll in 2013 Cyclone Phailin was 0.5% and the economic loss was about one-third of that during 1999. Concomitant improvements in the technological expertise of the early warning system, an integrated approach at all levels of administration including joint planning with major nongovernmental organizations, and improved community participation were identified as game-changers. An unbelievable 1 million people were evacuated to safety. CONCLUSIONS: Our essay aims to highlight key steps in this success and calls for futuristic approaches like insurance programs and gender-sensitive recovery plans. With thorough scrutiny, India's model may well stand to be replicated in resource-restricted settings.

Comparative study of tumor markers in patients with colorectal carcinoma before and after chemotherapy.

BACKGROUND: Colorectal carcinoma (CRC), the second leading cause of cancer-related deaths in US, has a rising time-trend in India. Tumour markers in CRC are extensively researched, and there's still debate on their diagnostic and prognostic values. METHODS: In this hospital-based longitudinal study in north India, 51 male diagnosed CRC cases (pre-chemotherapy) were contrasted against 50 age and sex matched controls. Nine biomarkers: carcinoembryonic antigen (CEA), prolactin (PRL), alfa feto protein (AFP), total human chorionic gonadotropin (hCG), cancer antigen-125 (CA-125), serum testosterone, prostate specific antigen (PSA) and ferritin were measured by direct chemiluminescence technique. Further, follow-up was done on 47 cases after treatment with six cycles of 5-flurouracil (5-FU) and oxaliplatin. RESULTS: Mean serum CEA (case: 5.94±8.27 ng/mL, control: 2.5±0.79 ng/mL, P<0.05), PRL (case: 28.12±13.39 ng/mL, control: 14.24±13.13 ng/mL, P<0.0001), AFP (case: 10.9±6.65 ng/mL, control: 4.02±1.26 ng/mL, P<0.0001) levels were significantly raised in CRC cases compared to controls. On the contrary, mean testosterone level (P<0.05) was lower among the cases. After chemotherapy, the mean serum CEA (P<0.05), AFP (P<0.0001) and CA-125 (P<0.05) levels among the cases decreased significantly compared to their pretreatment levels. CONCLUSIONS: The present study strongly indicates the role of CEA, PRL, AFP, CA-125 and testosterone as important biomarkers in male CRC patients from north India. Further, AFP, CA-125 and CEA may be used to assess the effectiveness of chemotherapy in such patients.

Dust explosion hazard of pulverized fuel carry-over.

This paper reports the results of experiments done to examine the explosibility of the waste products (fly ash and bottom ash) from pulverized fuels (coal and petroleum coke). Tests were conducted for the fly and bottom ashes alone and also for selected fly ashes blended with the fuels. The explosion parameters of interest were explosion pressure and rate of pressure rise. The fly ashes showed no propensity to explode, whereas one of the bottom ashes did show limited explosibility. Both findings can be explained with reference to the volatile matter content of the ashes. Admixture of either coal or petroleum coke with fly ash resulted in explosible mixtures at volatile contents in the range of 7-13%, with the value being dependent on the composition of the mixture components and their particle sizes.

Evaluating estradiol levels in male patients with colorectal carcinoma.

BACKGROUND: Globally more than 1 million people suffer from colorectal cancer (CRC) per annum, resulting in about 0.5 million deaths. The role of estrogen in CRC is being researched with great interest; expression of estrogen receptors (alfa and beta) is being explored. AIMS AND OBJECTIVE: Our objective was to compare the serum estradiol levels in diagnosed male patients of CRC, with age-matched controls; and to study the estradiol levels across the different stages of CRC. SETTING AND DESIGN: A cross-sectional study was conducted from January, 2012 to March, 2013 at a tertiary care hospital in north India. MATERIALS AND METHODS: Fifty one male preoperative CRC patients were enrolled along with 50 age-matched male controls. Ethical approval and informed written consent from each participant were duly obtained. CRC patients were staged as per TNM (T- Tumour, N- Node, M- Metastasis; I, II, III and IV) criteria. Serum estradiol level was measured by Chemiimmunofluroscence method (normal = 11.6 - 41.2 pg/ml). STATISTICAL ANALYSIS USED: We used student's t test and ANOVA (analysis of variance) to analyse the data (SPSS version 17.0, SPSS, Inc., Chicago, Illinois) Result: The mean serum estradiol level among CRC patients (43.4, sd=27.1) was significantly more than that among controls (mean=24.7, sd=17.5), (p<0.0001). Across the four TNM stages of CRC patients, mean estradiol level was highest in Stage II (55.9, sd=15.5); followed by Stages III (44.1, sd=24.9), IV (36.3, sd=30.0) and I (26.4, sd=38.8). However, significant difference was obtained only between Stages I and II. CONCLUSION: Our study revealed increased levels of serum estradiol in Indian male CRC patients. Further research is warranted to corroborate this finding, and to understand the role of estradiol across different TNM stages of CRC.