Pulmonary nodule detection in low dose computed tomography using a medical-to-medical transfer learning approach.

Purpose: Lung cancer is the second most common cancer and the leading cause of cancer death globally. Low dose computed tomography (LDCT) is the recommended imaging screening tool for the early detection of lung cancer. A fully automated computer-aided detection method for LDCT will greatly improve the existing clinical workflow. Most of the existing methods for lung detection are designed for high-dose CTs (HDCTs), and those methods cannot be directly applied to LDCTs due to domain shifts and inferior quality of LDCT images. In this work, we describe a semi-automated transfer learning-based approach for the early detection of lung nodules using LDCTs. Approach: In this work, we developed an algorithm based on the object detection model, you only look once (YOLO) to detect lung nodules. The YOLO model was first trained on CTs, and the pre-trained weights were used as initial weights during the retraining of the model on LDCTs using a medical-to-medical transfer learning approach. The dataset for this study was from a screening trial consisting of LDCTs acquired from 50 biopsy-confirmed lung cancer patients obtained over 3 consecutive years (T1, T2, and T3). About 60 lung cancer patients' HDCTs were obtained from a public dataset. The developed model was evaluated using a hold-out test set comprising 15 patient cases (93 slices with cancerous nodules) using precision, specificity, recall, and F1-score. The evaluation metrics were reported patient-wise on a per-year basis and averaged for 3 years. For comparative analysis, the proposed detection model was trained using pre-trained weights from the COCO dataset as the initial weights. A paired t-test and chi-squared test with an alpha value of 0.05 were used for statistical significance testing. Results: The results were reported by comparing the proposed model developed using HDCT pre-trained weights with COCO pre-trained weights. The former approach versus the latter approach obtained a precision of 0.982 versus 0.93 in detecting cancerous nodules, specificity of 0.923 versus 0.849 in identifying slices with no cancerous nodules, recall of 0.87 versus 0.886, and F1-score of 0.924 versus 0.903. As the nodule progressed, the former approach achieved a precision of 1, specificity of 0.92, and sensitivity of 0.930. The statistical analysis performed in the comparative study resulted in a p -value of 0.0054 for precision and a p -value of 0.00034 for specificity. Conclusions: In this study, a semi-automated method was developed to detect lung nodules in LDCTs using HDCT pre-trained weights as the initial weights and retraining the model. Further, the results were compared by replacing HDCT pre-trained weights in the above approach with COCO pre-trained weights. The proposed method may identify early lung nodules during the screening program, reduce overdiagnosis and follow-ups due to misdiagnosis in LDCTs, start treatment options in the affected patients, and lower the mortality rate.

Pediatric liver transplantation for autoimmune liver disease: Ten-year experience from a liver transplant center in India.

Liver transplantation (LT) has emerged as the best therapeutic modality for end-stage liver disease in pediatric autoimmune liver disease (AILD). We aimed to describe our experience of pediatric living donor liver transplantation for AILD from India over a period of 10 years. We did a retrospective analysis of 244 liver transplants at our center over the last 10 years to identify children with AILD (18 years or younger). We aimed to describe the demographic features, clinical profile, graft survival, patient outcome, and predictors of mortality in our cohort. Between July 2010 and May 2020, 13 liver transplants were performed for AILD out of total 244 children transplanted over the last 10 years at our center. Mean (standard deviation [SD]) age at LT was 12 (± 3.84) years. Leading indications for LT were decompensated liver disease (61.5%), acute-on-chronic liver failure (23.1%), acute liver failure (ALF) (7.7%), and recurrent cholangitis and growth failure (7.7%). Mean Pediatric End-stage Liver Disease (PELD) score/model for end-stage liver disease (MELD) score and international normalized ratio (INR) (SD) at presentation were 24 (± 12.81) and 2.48 (± 1.54), respectively. Median discharge duration was 23 days (interquartile range [IQR] 21-36 days). 30.7% (4/13) of the subjects had no postoperative complications. Diarrhea (15.3%), pneumonia (7.7%), jejunostomy site bleed (7.7%), tacrolimus toxicity (7.7%), and vascular complications (7.7%) were seen, which resolved with satisfactory graft function. Three subjects died post-LT; causes of death included sepsis (n=3), renal dysfunction (n=1), and pneumonia (n=1). Others have been well on follow-up with no graft rejection or need for re-transplantation. Overall, 1-year and 5-year patient survival rates were 76.9% and 70%, respectively. Lower platelet count, autoimmune hepatitis (AIH) 2, and PELD/MELD score were found to be significant predictors of mortality on univariate analysis, which were not significant on multivariate modelling. The complications, graft and patient survival rates in our experience were quite encouraging, and are comparable with the best centers worldwide. After instituting appropriate treatment, early referral of such patients to an equipped center should be facilitated.

Treatment of Hepatitis C in a Case of Pediatric B-Cell Acute Leukemia.

The prevalence of hepatitis C virus (HCV) infection in Pediatric patients with lymphoproliferative diseases has most commonly been reported with B cell Non-Hodgkin lymphoma. Case studies have reported the requirement of dose reduction or suspension of chemotherapy in 80% of Pediatric ALL cases who are anti-HCV positive owing to hepatotoxicity. The standard of care anti HCV therapy in children aged 3-17 years had been peginterferon and ribavirin for 48 weeks. FDA approved pan-genotypic, anti- HCV regimen, sofosbuvir/velpatasvir [SOF/VEL], for the Pediatric population >6yrs of age or >17 kg body weight in March 2020. We herein report a case of an HCV infected Pediatric B cell ALL patient who was treated with SOF/VEL concomitantly with an intensive chemotherapy regimen. Child tolerated the full dose chemotherapy along with antivirals for 12 weeks and was in morphological remission with sustained virological response.

Immunoexpression of PTEN, HER2/neu, and Ki-67 in endoscopic gastric carcinoma biopsies; their correlation with histological subtypes and one-year survival.

BACKGROUND: Gastric carcinoma is a major cause of cancer-related morbidity and mortality worldwide. Gastric neoplasms arise from genetic and epigenetic changes in various genes. Present study evaluates the immunoexpression of PTEN, HER2/neu, and Ki-67 in endoscopic gastric carcinoma biopsies and correlates the expression of these proteins with clinicopathological features. MATERIAL AND METHODS: Adequate endoscopic biopsies of 27 cases of gastric carcinoma were evaluated for World Health Organization (WHO) and Lauren's classification subtypes along with HER2/neu, PTEN, and Ki-67 immunoexpression. HER2/neu immunostaining was scored as proposed in the Trastuzumab for gastric cancer (ToGA) trial while PTEN staining and downregulation were assessed using an immunoreactive score. The cut-off for Ki-67 expression was taken as 90th percentile of the values in adjacent non-neoplastic tissue. All statistical analysis was done at 5% level of significance with SPSS v22 statistical software. RESULTS: Tubular adenocarcinoma was the commonest WHO histological subtype and 56% of cases were of intestinal type as per Lauren's classification. 55.6% of cases showed a complete loss of PTEN expression in neoplastic tissue. 17 of the 19 cases with adjacent non-neoplastic tissue showed PTEN downregulation in neoplastic tissue. 81.5% of cases had a high Ki-67 index and HER2/neu overexpression was noted in 36% of cases. All the four cases who died had high Ki-67 proliferation indices; 3 patients had loss of PTEN expression and HER2/neu overexpression. CONCLUSION: We conclude that these immunomarkers can play important role in the behavior of gastric carcinomas and can be targeted for new therapies.

Pulmonary alveolar microlithiasis: Blizzard of lung.

Pulmonary alveolar microlithiasis (PAM) is a rare inherited disorder in which patients present with either nonspecific signs and symptoms or are asymptomatic. Clinical-radiological dissociation is a commonly seen feature of the disease. Majority of cases are diagnosed in second and third decade of life, although presentation in paediatric and elderly population is also reported. Pathognomonic radiological findings, with normal calcium and phosphate levels can confirm the diagnosis without the need of further investigations in large number of cases. A high index of suspicion and knowledge of the disease is of paramount importance as it has a wide range of presentation and variable course thus posing a diagnostic challenge. We present two cases of this rare disease in elderly females with distinct presentations although with similar and characteristic radiological findings along with a brief review of literature of the disease.

An unusual case of unilateral hyperlucent lung.

Differential diagnoses of unilateral hyperlucent lung are expansive, ranging from soft tissue to pulmonary parenchyma. A systematic approach to interpretation of radiography guides us in quick localisation of the anatomical site of involvement. https://bit.ly/3fNy4vT.

Tropical pulmonary eosinophilia: effect of addition of corticosteroids after failure of diethylcarbamazine therapy.

Successful response in diethylcarbamazine (DEC) therapy in tropical pulmonary eosinophilia (TPE) is not universal with a 20-40% failure rates in chronic cases. Corticosteroids have been used in such patients. However, their role in management remains ill-defined. A patient of TPE with incomplete clinical, haematological and physiological response to a standard 3 weeks DEC therapy received additional corticosteroids for the next two cycles, after which complete remission occurred. However, there was a relapse two months later with evidence of a chronic state requiring further treatment with corticosteroids with good response.

Sequential occurrence of combined pulmonary fibrosis and emphysema syndrome in a non-smoker female patient.

The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking.

GOLD Classification of COPD: Discordance in Criteria for Symptoms and Exacerbation Risk Assessment.

The new A-B-C-D Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of chronic obstructive pulmonary disease (COPD) is based on combined symptoms and exacerbation risk assessment. The assumed equivalence between dyspnoea modified Medical Research Council (mMRC) grade ≥2 and COPD Assessment Test (CAT) score ≥ 10 to identify more symptoms has been questioned. Whether the exacerbation risk assessment criteria, old GOLD spirometry staging and frequency of exacerbations, are equivalent has not been examined. We evaluated the extent of agreement between these alternative criteria and whether it improved by redefining the equivalence between mMRC grade and CAT score. CAT scores, mMRC grades of dyspnoea, frequency of exacerbations and spirometry stages were computed in 400 patients with COPD. Receiver operating characteristic curve was analysed to determine the best CAT score to identify more symptoms. CAT scores across mMRC grades and the frequency of exacerbations across spirometry stages showed substantial overlaps. The symptoms criteria gave discordant classification in 88 (22%) patients (kappa 0.62) and the exacerbation risk assessment criteria in 181 (45%) patients (kappa 0.12). A CAT score of ≥10 had 82% sensitivity but 24% specificity to identify mMRC grade ≥ 2, while a score of 17 had 98% specificity but a low sensitivity of 52% and did not improve the agreement. We conclude that symptoms and exacerbation risk assessment criteria of the new GOLD classification yield discordant group categorisations. Lack of any satisfactory equivalence between CAT score and mMRC grades implies that the former cannot be used alone. Using the higher of mMRC ≥ 2 and CAT score ≥ 17 to identify more symptoms would avoid discordant categorisation.

Occupational bronchiolitis induced by cotton dust exposure in a nonsmoker.

The most well-known disease caused by cotton dust is byssinosis though it is also associated with chronic obstructive airways disease, and very rarely, interstitial lung disease. Obliterative bronchiolitis has never been reported in this setting. We report a 63-year-old, nonsmoker male, who presented with complaints of cough and exertional dyspnoea for 10 years. He had worked in textile industry for 35 years and symptoms had persisted even after quitting. Examination revealed prolonged expiration with expiratory wheeze, and pulmonary function tests revealed severe airflow limitation with air trapping and impaired diffusion capacity. Arterial blood gas analysis showed type I respiratory failure. A high resolution computed tomogram of the chest showed bilateral centrilobular nodules with tree-in-bud pattern and areas of air trapping. A diagnosis of obliterative bronchiolitis induced by cotton dust exposure was established on the basis of the occupational history and the characteristic radiological signs.

Occupational emphysema following long-term exposure to metal fumes during electroplating in a non-smoker.

Exposure to cigarette smoke is by far the most common causative factor for chronic obstructive pulmonary disease. Occupational exposure to fumes, chemicals, dusts and environmental pollution is also an important cause of chronic productive cough. Emphysema developing as a consequence of an occupational exposure is extremely rare. We describe the rare occurrence of severe emphysema in a non-smoker male who had worked for nearly three decades in nickel electroplating industry.

Lipoprotein lipase is an important modulator of lipid uptake and storage in hypothalamic neurons.

LPL is the rate-limiting enzyme for uptake of TG-derived FFA in peripheral tissues, and the enzyme is expressed in the brain and CNS. We previously created a mouse which lacks neuronal LPL. This animal becomes obese on a standard chow, and we observed reduced lipid uptake in the hypothalamus at 3 months preceding obesity. In our present study, we replicated the animal phenotype in an immortalized mouse hypothalamic cell line (N41) to examine how LPL affects expression of AgRP as well as entry and storage of lipids into neurons. We show that LPL is able to modulate levels of the orexigenic peptide AgRP. LPL also exerts effects on lipid uptake into culture neurons, and that uptake of neutral lipid can be enhanced even by mutant LPL lacking catalytic activity. N41 cells also accumulate neutral lipid in droplets, and this is at least in part regulated by LPL. These data in addition to those published in mice with neuron-specific deletion of LPL suggest that neuronal LPL is an important regulator of lipid homeostasis in neurons and that alterations in LPL levels may have important effects on systemic metabolism and neuronal lipid biology.

Femtosecond Nanoplasmonic Dephasing of Individual Silver Nanoparticles and Small Clusters.

We present experimental measurements of localized surface plasmon emission from individual silver nanoparticles and small clusters via accurately delayed femtosecond laser pulses. Fourier transform analysis of the nanoplasmonic coherence oscillations reveals different frequency components and dephasing rates for each nanoparticle. We find three different types of behavior: single exponential decay, beating between two frequencies, and beating among three or more frequencies. Our results provide insight into inhomogeneous and homogeneous broadening mechanisms in nanoplasmonic spectroscopy that depend on morphology and nearby neighbors. In addition, we find the optical response of certain pairs of nanoparticles to be at least an order of magnitude more intense than the response of single particles.

Biological imaging with coherent Raman scattering microscopy: a tutorial.

Coherent Raman scattering (CRS) microscopy is gaining acceptance as a valuable addition to the imaging toolset of biological researchers. Optimal use of this label-free imaging technique benefits from a basic understanding of the physical principles and technical merits of the CRS microscope. This tutorial offers qualitative explanations of the principles behind CRS microscopy and provides information about the applicability of this nonlinear optical imaging approach for biological research.

Achromatic miniature lens system for coherent Raman scattering microscopy.

We discuss the design and performance of a miniature objective lens optimized for coherent Raman scattering microscopy. The packaged lens assembly has a numerical aperture of 0.51 in water and an outer diameter of 8 mm. The lens system exhibits minimum chromatic aberrations, and produces coherent Raman scattering images with sub-micrometer lateral resolution (0.648 µm) using near-infrared excitation pulses. We demonstrate that despite the small dimensions of the miniature objective, the performance of this lens system is comparable to standard microscope objective lenses, offering opportunities for miniaturizing coherent Raman scattering imaging probes without sacrificing the image quality.

Evaluation of stimulated Raman scattering microscopy for identifying squamous cell carcinoma in human skin.

BACKGROUND AND SIGNIFICANCE: There is a need to develop non-invasive diagnostic tools to achieve early and accurate detection of skin cancer in a non-surgical manner. In this study, we evaluate the capability of stimulated Raman scattering (SRS) microscopy, a potentially non-invasive optical imaging technique, for identifying the pathological features of s squamous cell carcinoma (SCC) tissue. STUDY DESIGN: We studied ex vivo SCC and healthy skin tissues using SRS microscopy, and compared the SRS contrast with the contrast obtained in reflectance confocal microscopy (RCM) and standard histology. RESULTS AND CONCLUSION: SRS images obtained at the carbon-hydrogen stretching vibration at 2945 cm(-1) exhibit contrast related protein density that clearly delineates the cell nucleus from the cell cytoplasm. The morphological features of SCC tumor seen in the SRS images show excellent correlation with the diagnostic features identified by histological examination. Additionally, SRS exhibits enhanced cellular contrast in comparison to that seen in confocal microscopy. In conclusion, SRS represents an attractive approach for generating protein density maps with contrast that closely resembles histopathological contrast of SCC in human skin.

In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin.

We employ a clinical multiphoton microscope to monitor in vivo and noninvasively the changes in reduced nicotinamide adenine dinucleotide (NADH) fluorescence of human epidermal cells during arterial occlusion. We correlate these results with measurements of tissue oxy- and deoxyhemoglobin concentration during oxygen deprivation using spatial frequency domain imaging. During arterial occlusion, a decrease in oxyhemoglobin corresponds to an increase in NADH fluorescence in the basal epidermal cells, implying a reduction in basal cell oxidative phosphorylation. The ischemia-induced oxygen deprivation is associated with a strong increase in NADH fluorescence of keratinocytes in layers close to the stratum basale, whereas keratinocytes from epidermal layers closer to the skin surface are not affected. Spatial frequency domain imaging optical property measurements, combined with a multilayer Monte Carlo-based radiative transport model of multiphoton microscopy signal collection in skin, establish that localized tissue optical property changes during occlusion do not impact the observed NADH signal increase. This outcome supports the hypothesis that the vascular contribution to the basal layer oxygen supply is significant and these cells engage in oxidative metabolism. Keratinocytes in the more superficial stratum granulosum are either supplied by atmospheric oxygen or are functionally anaerobic. Based on combined hemodynamic and two-photon excited fluorescence data, the oxygen consumption rate in the stratum basale is estimated to be ∼0.035 µmoles/10(6) cells/h.