CT coronary angiography as an alternative imaging method to ascertain cardiac output and its correlation with echocardiography.

AIM: To assess the feasibility and accuracy of cardiac output (CO) obtained using a test bolus in patients scanned with single-source prospective-gated cardiac computed tomography (CT), and comparing it with CO obtained from unenhanced two-dimensional (2D) echocardiography using biplane Simpson's method. MATERIALS AND METHODS: In the present study, 100 patients with a mean age of 55 ± 12 years who underwent coronary CT angiography with prospective electrocardiogram (ECG)-gated CT in which the scan delay was evaluated using a test bolus. The time-attenuation curves obtained from the test bolus were used to calculate the CO of the patients. The CO obtained was then compared with that obtained after follow-up 2D echocardiography using biplane modified Simpson method. RESULTS: Linear regression was calculated between the CO and contrast enhancement: CO = -0.16(HUmax) + 7.65. The study showed good correlation between the two methods with r=0.77, p<0.001. On Bland-Altman analysis, no significant difference was noted between the two methods. CONCLUSION: This less researched method for CO estimation appears feasible; however, the clinical usefulness of this parameter is uncertain in absence of further clinical and reference standard validation.

Redefining the importance of polylactide-co-glycolide acid (PLGA) in drug delivery.

The limitations of non-biodegradable polymers have paved the way for biodegradable polymers in the pharmaceutical and biomedical sciences over the years. Poly (lactic-co-glycolic acid) (PLGA), also known as "Smart polymer", is one of the most successfully developed biodegradable polymers due to its favorable properties, such as biodegradability, biocompatibility, controllable drug release profile, and ability to alter surface with targeting agents for diagnosis and treatment. The release behavior of drugs from PLGA delivery devices is influenced by the physicochemical properties of PLGA. In this review, the current state of the art of PLGA, its synthesis, physicochemical properties, and degradation are discussed to enunciate the boundaries of future research in terms of its applicability with the optimized design in today's modern age. The fundamental objective of this review is to highlight the significance of PLGA as a polymer in the field of cancer, cardiovascular diseases, neurological disorders, dentistry, orthopedics, vaccine therapy, theranostics and lastly emerging epidemic diseases like COVID-19. Furthermore, the coverage of recent PLGA-based drug delivery systems including nanosystems, microsystems, scaffolds, hydrogels, etc. has been summarized. Overall, this review aims to disseminate the PLGA-driven revolution of the drug delivery arena in the pharmaceutical and biomedical industry and bridge the lacunae between material research, preclinical experimentation, and clinical reality.

The incidence of immunofluorescence patterns and specific autoantibodies observed in autoimmune patients in a tertiary care centre.

Summary: Objectives: Testing for antinuclear antibodies (ANA) facilitates the diagnosis of autoimmune diseases (ADs). Here, we report an incidence of ANA positivity and its patterns by indirect immunofluorescence (IIF) and specific autoantibodies through immunodot assay. Methods: Sera from 993 patients presenting with various ADs were tested by IIF and immunodot assay. Results: ANAs were detected in 39.7%, of which speckled pattern was predominantly observed (50.8%). 56.8% of samples were positive on the immunodot assay with SSA Ro 60 antibody being the most prevalent (30.7%). Discussion: A significant correlation (p minor 0.0001) was observed between patterns and auto-antibodies. Coarse speckled (CS) and homogeneous were overly represented by antibodies SSA Ro 60 (13%) and nucleosomes (5.8%) respectively. Mi-2, PL-7, PL-12, and SP-100 were the rarest autoantibodies specificities found. Conclusions: The presence of a particular IIF pattern is predictive of a specific autoantibody in the sample. Association of IIF patterns and specific autoantibody are relevant for a more accurate diagnosis of disease.

Late onset systemic sclerosis with seronegativity: a rare presentation of an uncommon disease.

Systemic sclerosis (SSc) is an uncommon connective tissue disorder characterized by multisystem involvement with fibrosis of skin and internal organs. Antibody formation is one of the hallmarks of SSc. Antinuclear antibodies (ANA) are positive in 97% of patients with SSc. We report a rare case where the patient was negative for ANA, Anti-topoisomerase I, Anti-centromere and Anti-RNA polymerase III antibodies.

Cytopathology of non-invasive follicular thyroid neoplasm with papillary-like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants.

OBJECTIVE: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently described, indolent thyroid tumor, with well-defined histopathological diagnostic criteria. Cytology features are not well documented. We reviewed cytology of histologically proven cases of NIFTP and some of its common differentials to look for salient diagnostic features. METHODS: Cases reported on histopathology as follicular variant of papillary thyroid carcinoma (FVPTC), or NIFTP between July 2015 and April 2017 having available cytology smears were retrieved and reclassified as NIFTP, FVPTC, and classical papillary thyroid carcinoma with predominant follicular pattern (PTC-FP). Cytological features were assessed, classified as per The Bethesda System for Reporting Cytopathology and compared. RESULTS: There were 23 NIFTP cases, 18 FVPTC and 8 PTC-FP. A microfollicle-predominant pattern was seen in all. Nuclear score was 2 in most NIFTP cases (61%). Pseudoinclusions were absent. NIFTP showed features of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (III) in 61%, follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) (IV) in 35% and suspicious for malignancy (SFM) (V) in 4%. Most of the FVPTCs were also called FN/SFN (IV) (56%) or AUS/FLUS (III) (22%). Nuclear features did not statistically differ from NIFTP. PTC-FP showed high-grade cytology in 75%, and higher nuclear score (3 in 75%) in contrast to NIFTP (P = .003). CONCLUSION: NIFTP and FVPTC show a similar distribution among the Bethesda categories hence precluding conclusive distinction on cytology. PTC-FP, in contrast, was found to have a statistically significant higher nuclear score and more commonly showed malignant cytology.

Adenocarcinoma predominant pattern subtyping and nuclear grading in cytology: Is there a role in prognostication of advanced pulmonary adenocarcinomas?

INTRODUCTION: Primary lung adenocarcinomas (ADs) show varied architectural patterns, and pattern-based subtyping of ADs is currently recommended due to prognostic implications. Predicting AD patterns on cytology is challenging; however, cytological nuclear features appear to correlate with histological grade and survival in early stage lung ADs. The feasibility and value of AD pattern prediction and nuclear grading on cytology in advanced lung ADs is not known. We aimed to predict patterns and analyse nuclear features on cytology and evaluate their role in prognostication. METHODS: One-hundred patients of Stage III/IV lung AD with available matched cytology and histology samples were included. Cyto-patterns based on cell arrangement patterns (flat sheets vs three-dimensional clusters vs papillae) and cyto-nuclear score based on nuclear features (size, shape, contour), nucleoli (macronucleoli vs prominent vs inconspicuous), and nuclear chromatin were determined, and correlated with predominant histological-pattern observed on the matched small biopsy and outcome. RESULTS: Higher cyto-nuclear scores were observed with high-grade histo-patterns (solid, micropapillary and cribriform), while the predicted cyto-patterns did not correspond to the predominant pattern on histology in 77% cases. Highest cyto-histo agreement was observed for solid pattern (72%). High grade histo-patterns and cyto-nuclear scores > 3 showed a trend towards inferior survival (not significant). CONCLUSIONS: Nuclear grade scoring on cytology is simple to perform, and is predictive of high grade patterns. Its inclusion in routine reporting of cytology samples of lung ADs may be valuable.

Focused cardiac ultrasound is feasible in parturients; a prospective observational study.

BACKGROUND: In pregnancy, the major causes of morbidity and mortality include diseases that affect circulation profoundly and restoration of normal circulation is a key objective. Focused cardiac ultrasound provides information on the individual determinants of circulation and has a significant impact on patient management. This study aimed to determine the feasibility of focused cardiac ultrasound in term parturients. METHODS: Forty parturients underwent focused cardiac ultrasound. Parasternal long-axis, parasternal short-axis, 4-chamber and subcostal views were performed in the left-lateral position and the supine position by a novice operator. All images were graded on the following scale: 1 = no image; 2 = poor and insufficient image; 3 = sufficient image quality; 4 = good image quality; 5 = perfect image quality. A cut-off grade of three signified images sufficient for clinical decision-making. RESULTS: Images sufficient for clinical decision-making were obtained in all patients when including all imaging views. 37/40 (93 %) patients presented images of grade ≥ 4, whereas 10/40 (25%) patients had images of grade 5. Image grades were higher in the left lateral position (all P < 0.001). Parturients with a body mass index ≤ 30 kg/m2 did not present different image grades than parturients with a higher body mass index (P = 0.753). Subcostal views could not be obtained. CONCLUSION: Focused cardiac ultrasound is feasible in the obstetric population and images of sufficient quality for clinical decision-making were obtained in all parturients by an operator with limited experience.

An institutional experience with The Paris System: A paradigm shift from ambiguous terminology to more objective criteria for reporting urine cytology.

BACKGROUND: Urine cytology is a highly specific modality for diagnosing high-grade urothelial carcinoma (HGUC), but plagued by low sensitivity and wide inter-observer variability mainly ascribed to the lack of an established template of reporting. The Paris System (TPS) working group proposed such a template at the 2013 International Congress of Cytology, replete with objective criteria for categorising specimens into one of the seven categories: non-diagnostic, negative for HGUC, atypical urothelial cells, suspicious for HGUC, HGUC, low-grade urothelial neoplasm and others (including non-malignant entities). This study was undertaken to determine the impact of TPS criteria in the morphological interpretation of urine samples. METHODS: A total of 255 voided urine specimens from 97 patients who had follow-up biopsies were re-assessed according to TPS criteria and correlated with the final histological diagnosis. RESULTS: Sixty-three patients were diagnosed with HGUC, and 34 had low-grade papillary UC on biopsy. Earlier samples from 40 (41.2%) patients were categorised as merely "atypical" wheereas the "positive for malignancy" category was assigned to 33 (34%) patients. After re-evaluation of the same cases using TPS criteria, cytological features in 44 (69.8%) out of 63 HGUC patients were correctly recognised as HGUC and samples from additional seven patients were re-categorised as suspicious for HGUC (total 81%). The sensitivity of the HGUC category in predicting HGUC was 69.8% which rose to 81% when HGUC was grouped with suspicious for HGUC category. CONCLUSION: The criteria outlined by TPS facilitated the standardisation of urine cytology reporting and significantly increased the sensitivity of diagnosing HGUC.

p40 in metastatic pulmonary trophoblastic tumour: potential diagnostic pitfall on histopathology.

p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. We describe a case in which lung tumour was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. A 36-year-old lady presented with cough and left sided chest pain of 2 months duration. Chest imaging revealed a lesion in left lower lobe of the lung and biopsy was suggestive of squamous cell carcinoma. However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She also had a history of hysterectomy five years ago, details of which were not available. Post-amputation ß-hCG levels were high and she had been treated with multimodality chemotherapy for choriocarcinoma. She had good response to chemotherapy initially, however became resistant later on. Review of the lung biopsy in the light of the past history along with extensive literature review led to the final diagnosis of metastatic trophoblastic tumour to lung. Hence, awareness that p40 immunopositivity can be seen in trophoblastic tumours is essential to avoid misdiagnosis, especially in sites like the lung where squamous cell carcinoma is common.

Record power, ultra-broadband supercontinuum source based on highly GeO2 doped silica fiber.

We demonstrate highly germania doped fibers for mid-infrared supercontinuum generation. Experiments ensure a highest output power of 1.44 W for a broadest spectrum from 700 nm to 3200 nm and 6.4 W for 800 nm to 2700 nm from these fibers, while being pumped by a broadband Erbium-Ytterbium doped fiber based master oscillator power amplifier. The effect of repetition frequency of pump source and length of germania-doped fiber has also been investigated. Further, germania doped fiber has been pumped by conventional supercontinuum source based on silica photonic crystal fiber supercontinuum source. At low power, a considerable broadening of 200-300 nm was observed. Further broadening of spectrum was limited due to limited power of pump source. Our investigations reveal the unexploited potential of germania doped fiber for mid-infrared supercontinuum generation. These measurements ensure the potential of germania based photonic crystal fiber or a step-index fiber supercontinuum source for high power ultra-broad band emission being by pumped a 1060 nm or a 1550 nm laser source. To the best of our knowledge, this is the record power, ultra-broadband, and all-fiberized supercontinuum light source based on silica and germania fiber ever demonstrated to the date.

Exploiting the short wavelength gain of silica-based thulium-doped fiber amplifiers.

Short wavelength operation (1650-1800 nm) of silica-based thulium-doped fiber amplifiers (TDFAs) is investigated. We report the first demonstration of in-band diode-pumped silica-based TDFAs working in the 1700-1800 nm waveband. Up to 29 dB of small-signal gain is achieved in this spectral region, with an operation wavelength accessible by diode pumping as short as 1710 nm. Further gain extension toward shorter wavelengths is realized in a fiber laser pumped configuration. A silica-based TDFA working in the 1650-1700 nm range with up to 29 dB small-signal gain and noise figure as low as 6.5 dB is presented.

Non-invasive quantification of hepatic steatosis in living, related liver donors using dual-echo Dixon imaging and single-voxel proton spectroscopy.

AIM: To evaluate the diagnostic implications of hepatic fat fraction calculated using dual-echo Dixon imaging and (1)H magnetic resonance spectroscopy (MRS) to detect hepatic steatosis in potential liver donors using histopathology as the reference standard. MATERIALS AND METHODS: One hundred and forty-five potential liver donors were included in the study. Magnetic resonance imaging (MRI) was performed using a 1.5 T system using a three-dimensional dual-echo MRI sequence with automated reconstruction of in-phase (IP), out-of-phase (OP), fat-signal-only, and water-signal-only images. Hepatic fat fraction was calculated by drawing 15 regions of interest on the IP, OP, fat-only, and water-only images. Single-voxel MRS was performed at echo times (TEs) of 30 ms in the right and left lobes of liver. Liver fat fraction was calculated from water and fat peaks. One hundred and forty-five biopsies were prospectively evaluated for steatosis by a pathologist using traditional determination of the cell-count fraction. MRI and pathology values of steatosis were correlated using Pearson's correlation coefficient. The sensitivity and specificity of each of these methods was calculated using histopathology as the reference standard. Reproducibility was assessed in 40 patients who had repeat scanning within 4-40 days. Measurement error was calculated from the coefficient of variation (CoV) with histopathologically proven <5% fat (n=112). RESULTS: The Bland-Altman limits of agreement with 95% confidence intervals (CI) was -2.9 to 5.3%. The intraclass correlation coefficient (ICC) for interobserver variability and reproducibility was 0.94 (95% CI: 0.91-0.97), 0.92 (95% CI: 0.91-0.97). The CoV was 7.6% (95% CI: 3.4-11.85). The area under the receiver operating characteristic (ROC) curve (AUC) for Dixon imaging 0.89 (95% CI: 0.87-0.91), for MRS 0.88 (95% CI: 0.86-0.90). The sensitivity for detecting <5% fat was 84% and specificity was 90%. CONCLUSION: Combination of dual-echo Dixon imaging and proton MRS is a useful tool for the preoperative diagnosis of hepatic steatosis in potential living liver donors. This can help avoid unnecessary biopsies in these patients.

Cytomorphology of neuroendocrine tumours of the gallbladder.

OBJECTIVE: Gallbladder neuroendocrine tumours (GB-NETs) are rare and account for 0.5% of all NETs. GB-NETs have an aggressive behaviour, which depends on the tumour grade. The cytomorphological spectrum of these tumours has never been described in detail. The present study evaluates the cytological features of GB-NETs and grades them according to the World Health Organization (WHO) classification. Furthermore, the expression of thyroid transcription factor-1 (TTF-1) has not been investigated previously in GB-NETs, although found in a subset of extrapulmonary NETs. METHODS: Twenty cases of GB-NET among 875 gallbladder carcinomas diagnosed by ultrasound-guided fine needle aspiration cytology (FNAC) over a period of nearly 4 years were studied. The following parameters were evaluated: architectural pattern, nuclear chromatin, nucleoli, mitoses, necrosis, moulding, apoptosis and smudge cells. Cases were categorized into well-differentiated (grades 1 and 2), small cell carcinoma (SCC) (grade 3) and mixed adenoneuroendocrine carcinoma. Nuclear positivity for TTF-1 was considered as positive. RESULTS: Morphologically, tumour cells were mainly arranged in rosettes in the well-differentiated category; sudden anisonucleosis and rare nuclear moulding with or without mitotic figures were other features. Eleven cases of SCC showed prominent nuclear moulding with frequent smudge cells, mitoses, apoptosis and necrosis. Three mixed adenoneuroendocrine carcinomas showed papillary fragments and an acinar arrangement of tumour cells. Four of the nine SCCs in which TTF-1 was evaluated on de-stained smears showed nuclear positivity. Histopathology was available in two SCCs and showed morphology similar to FNAC. CONCLUSION: Cytology plays an important role in the diagnosis of GB-NETs for appropriate subtype characterization, which is necessary for the prognostication of these tumours. TTF-1 may not be used for the differentiation of gallbladder SCCs from pulmonary SCCs.

Fine needle aspiration cytology features of poorly differentiated thyroid carcinoma.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) is an uncommon thyroid malignancy with biological behaviour intermediate between well-differentiated and undifferentiated thyroid carcinoma. The cytological diagnosis of PDTC is often difficult as a result of a lack of well-established cytomorphological features and a considerable degree of morphological overlap with other commoner thyroid neoplasms. OBJECTIVE: To review the cytomorphological features of PDTC with the aim of highlighting salient diagnostic morphological features and differential diagnostic problems. METHODS: Seven cases of histologically proven PDTC with available aspiration cytology smears were reviewed for the presence of distinguishing cytomorphological features. RESULTS: The architectural arrangement of tumour cells was the most important diagnostic parameter. Cellular nests, three-dimensional clusters dyscohesive aggregates and singly dispersed cells in the background were present in all cases. A unique 'garlanded appearance', owing to the peripheral orientation of nuclei within the tumour cell clusters, was noted (71.4%) along with the presence of basement membrane-like material (71.4%). Transgressing vessels (85.7%) and endothelial wrapping of cell clusters (71.4%) were also noted. Interestingly, most cases lacked necrosis and mitotic activity that are included in the histological diagnostic criteria for PDTC. CONCLUSION: Although PDTC has considerable cytomorphological overlap with well-differentiated thyroid tumours, this present study highlights certain cytomorphological features that may suggest the correct pre-operative diagnosis, important for the appropriate management.

Isolated oculocutaneous sarcoidosis in a teenage male: a rare case report.

Sarcoidosis is an inflammatory disease with multisystem involvement characterized by the presence of noncaseating granulomas. It can affect virtually every organ of the body, with lung involvement being most common occurring in >90% of patients. Other organs affected are skin, eye and liver. Skin involvement is common, affecting 25-35%. Here we present a rare case of a 15 year-old male with isolated oculocutaneous sarcoidosis without systemic involvement.

Systemic lupus erythematosus presenting as fulminant lupus pneumonitis: a rare case report.

We report a case of 19 year-old female patient diagnosed as systemic lupus erythematosus (SLE) presented with fever and diffuse cutaneous lesions. During the hospital stay she had acute pneumonia, pleural effusion and respiratory failure, which required intensive care unit (ICU) care and mechanical ventilator support. A fulminant course of the disease, decreased values of complement levels and positive antinuclear antibodies (ANA) in pleural fluid and repeated negative sputum for acid-fast bacillus, blood cultures enabled diagnosis of fulminant lupus pneumonitis. Fulminant lupus pneumonitis is a rare but potentially life threatening complication of SLE. Management requires involvement of multiple specialties and rigorous efforts in reviving the patient.

Highly efficient Yb-free Er-La-Al doped ultra-low NA large mode area single-trench fiber laser.

We demonstrate a 60µm core diameter Yb free Er-La-Al doped single-trench fiber having a 0.038 ultra-low-NA, fabricated using conventional MCVD process in conjunction with solution doping technique. Numerical simulations predict an effective single mode operation with effective area varying from 1,820µm(2) to 1,960µm(2) (taking bend-induced modal distortion into account) for different thicknesses of trenches and resonant rings at a constant bend radius of 25cm. Moreover, all solid structure favors easy cleaving and splicing. Experimental measurements demonstrate a robust effective single mode operation. Furthermore, with a 4%-4% laser cavity, this fiber shows a record efficiency of 46% with respect to the absorbed pump power.

Large mode area multi-trench fiber for UV and visible transmission.

We experimentally demonstrate all-solid 10 and 20 µm core diameter multi-trench fibers for UV and visible wavelengths. Measurements ensure an effective single-mode operation over a wide range of bend radii, which is suitable for applications such as beam delivery. Both fibers were fabricated by the conventional modified chemical vapor deposition process, which is suitable for mass production. Moreover, all-solid fiber design ensures easy cleaving and splicing.

High power, compact, picosecond MOPA based on single trench fiber with single polarized diffraction-limited output.

We experimentally demonstrate an all-solid Yb-doped 30 µm core diameter single trench fiber. Measurements ensure a robust effective single-mode operation without the need of tight coiling as required for conventional fibers thanks to the ultralow NA (∼0.038) and resonant ring surrounding the core. All-solid and cylindrical design ensures the suitability for mass scale production with the added benefit of all-fiberized device structure. A compact master oscillator power amplifier (MOPA) has been built using this fiber delivering ∼23.5 ps pulses at 13.5 MHz repetition rate delivering up to ∼52 W of average output power corresponding to a pulse energy of ∼3.8 µJ and peak power of >160 kW, while maintaining ∼76% slope efficiency. The output beam exhibits a polarization extinction ratio of more than 15 dB and a M2 less than 1.15.

Differentiation of histoplasma and cryptococcus in cytology smears: a diagnostic dilemma in severely necrotic cases.

OBJECTIVE: The correct identification of fungal organisms is important for the appropriate clinical management of patients. It becomes difficult in necrotic smears when the tissue response is not clearly discernible. It is difficult to distinguish between histoplasma and cryptococcus in severely necrotic cases, where both appear as variably sized clear refractile haloes. METHODS: Four cases of adrenal necrotic histoplasma infection were studied and the morphology was compared with that of non-necrotic histoplasmosis and cases of cryptococcal infection. Eleven cases were analysed in fine needle aspiration cytology (FNAC) smears. Ziehl-Neelsen (ZN) stain was performed to exclude tuberculosis in necrotic smears. A clinical and serology correlation was performed where available. RESULTS: Necrotic cases of histoplasma infection revealed negative refractile clear haloes similar to those of cryptococcus. Histoplasma showed methylene blue-stained organisms in ZN stains, whereas the cryptococcus cases were negative. Similar methylene blue-stained organisms were seen in non-necrotic histoplasma infection. CONCLUSION: As a result of morphological overlap between cryptococcus and histoplasma, the distinction between the two fungi can be difficult in many cases. ZN staining appears to have a role in the differentiation of these fungi in severely necrotic cases. This observation needs to be validated on a larger number of cases with complete correlation with clinical, serology and treatment records.