Auditory toxicity in late preterm and term neonates with severe jaundice.

AIM: Jaundice may cause auditory toxicity (auditory neuropathy and hearing loss). However, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. We compared TSB, bilirubin:albumin molar ratio (BAMR), and unbound bilirubin for their association with auditory toxicity in neonates with severe jaundice (TSB ≥342µmol/L, or that met exchange transfusion). METHOD: Neonates greater or equal to 34 weeks gestational age with severe jaundice during the first 2 postnatal weeks were eligible for prospective cohort study, unless they had craniofacial malformations, chromosomal disorders, toxoplasmosis, other infections, rubella, cytomegalovirus, herpes simplex infections, surgery, or family history of congenital deafness. RESULTS: Twenty-eight out of 100 neonates (mean gestational age 37.4wks; 59 males, 41 females) had auditory toxicity. Peak unbound bilirubin, but not peak TSB and BAMR, was associated with auditory toxicity (p<0.05) in neonates with severe (TSB <427.5µmol/L) and extreme hyperbilirubinemia (TSB ≥427.5µmol/L). Area under the receiver operating characteristic curve for unbound bilirubin (0.78) was significantly greater (p=0.03) than TSB (0.54) among neonates with severe but not extreme hyperbilirubinemia. INTERPRETATION: Unbound bilirubin is more strongly associated with auditory toxicity than TSB and/or BAMR in greater or equal to 34 weeks gestational age neonates with severe jaundice. Unbound bilirubin is a better predictor than TSB in neonates with severe hyperbilirubinemia.

Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients from northern India.

BACKGROUND: Molecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene-rearrangements, PTEN deletion, and SPINK1 over-expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over-expression, and PTEN deletion in this cohort. METHODS: In this multi-center study, formalin-fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA-ISH) and/or fluorescence in situ hybridization (FISH). RESULTS: ERG over-expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA-ISH, no alteration in ETV4 was observed. SPINK1 over-expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG-positive cases (P = 0.017) but in only one case with SPINK1 over-expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in ∼1% and ∼4.5% of the PCa cases, respectively. CONCLUSIONS: This is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over-expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in clinical decision-making for the pursuit of surgery, diagnosis, and in selection of therapeutic intervention.

A study of self-perception and communication success as perceived by adolescents with cochlear implants and their significant others.

OBJECTIVES: The objectives of this prospective, cross-sectional study were to compare self-perception and communication-success ratings of adolescents with cochlear implant (AWCI) and their caregivers (C-AWCI) and to explore associations with age at CI, implant age, and chronological age. METHOD: Fourteen CI centers across India participated. The Think About it Quiz (TAIQ), Self Assessment of Communication-Adolescent (SAC-A), and Significant Other Assessment of Communication-Adolescent (SOAC-A) were translated into five languages. Data were collected from 173 AWCI aged 10;0-19;6 years and an associated caregiver for each participant. RESULTS: On the TAIQ, self-ratings by AWCI were significantly lower than the ratings by C-AWCI. Peer acceptance correlated with athletic competence for both groups. For the SAC-A versus SOAC-A, there was no significant difference between AWCI and C-AWCI ratings. Except for a negative correlation between peer-acceptance and chronological age for caregiver ratings, no other associations were found between any other ratings and age at CI, implant age, and chronological age. CONCLUSIONS: Caregiver judgments of their adolescents with CI were not in equal agreement with self-ratings by the adolescents across various aspects of performance. Caregivers appeared to underestimate the self-perception issues faced by adolescents with CI but had excellent agreement with their adolescents' self-rating of communication success. The inclusion of activities to improve children's participation in sports could possibly improve peer acceptance.

Concentration of FAD as a marker for cervical precancer detection.

We report the ex vivo results of an in-house fabricated portable device based on polarized fluorescence measurements in the clinical environment. This device measures the polarized fluorescence and elastic scattering spectra with 405-nm laser and white light sources, respectively. The dominating fluorophore with 405-nm excitation is flavin adenine dinucleotide (FAD) with a fluorescence peak around 510 nm. The measured spectra are highly modulated by the interplay of scattering and absorption effects. Due to this, valuable information gets masked. To reduce these effects, intrinsic fluorescence was extracted by normalizing polarized fluorescence spectra with polarized elastic scattering spectra obtained. A number of fluorophores contribute to the fluorescence spectra and need to be decoupled to understand their roles in the progression of cancer. Nelder-Mead method has been utilized to fit the spectral profile with Gaussian to decouple the different bands of contributing fluorophores (FAD and porphyrin). The change in concentration of FAD during disease progression manifests in the change in ratio of total area to FWHM of its Gaussian profile. Receiver operating characteristic (ROC) curve analysis has been used to discriminate different grades of cervical precancer by using the ratio as input parameter. The sensitivity and specificity for discrimination of normal samples from CIN I (cervical intraepithelial neoplasia) are 75% and 54%, respectively. Further, the normal samples can be discriminated from CIN II samples with 100% and 82% sensitivity and specificity, respectively, and the CIN I from CIN II samples can also be discriminated with 100% sensitivity and 90% specificity, respectively. The results show that the change in the concentration of (FAD) can be used as a marker to discriminate the different grades of the cancer and biochemical changes at an early stage of the cancer can also be monitored with this technique.

Intrinsic fluorescence for cervical precancer detection using polarized light based in-house fabricated portable device.

An in-house fabricated portable device has been tested to detect cervical precancer through the intrinsic fluorescence from human cervix of the whole uterus in a clinical setting. A previously validated technique based on simultaneously acquired polarized fluorescence and polarized elastic scattering spectra from a turbid medium is used to extract the intrinsic fluorescence. Using a diode laser at 405 nm, intrinsic fluorescence of flavin adenine dinucleotide, which is the dominant fluorophore and other contributing fluorophores in the epithelium of cervical tissue, has been extracted. Different grades of cervical precancer (cervical intraepithelial neoplasia; CIN) have been discriminated using principal component analysis-based Mahalanobis distance and linear discriminant analysis. Normal, CIN I and CIN II samples have been discriminated from one another with high sensitivity and specificity at 95% confidence level. This ex vivo study with cervix of whole uterus samples immediately after hysterectomy in a clinical environment indicates that the in-house fabricated portable device has the potential to be used as a screening tool for in vivo precancer detection using intrinsic fluorescence.

Determination of p16 overexpression as an indicator of human papillomavirus infection in oral dysplasia and carcinoma.

CONTEXT: Oral and pharyngeal cancer, grouped together, is the sixth most common cancer in the world. In the past few years, human papillomavirus (HPV) infection has been suggested as a risk factor for oral cancer apart from traditional risk factors such as smoking, tobacco, and alcohol consumption. AIMS: The aim of this study was to determine HPV status of the tumors using polymerase chain reaction (HPV-DNA PCR) and p16 immunostaining and to correlate p16 overexpression as an indicator of HPV-associated oral dysplasia and carcinoma. SETTINGS AND DESIGN: A prospective study was conducted in fifty cases of suspected oral cancer. MATERIALS AND METHODS: PCR Amplification of extracted HPV-DNA was done for HPV-DNA status in fresh tissue of suspected oral cancer cases. Histomorphological features of the cases were analyzed, and p16 immunohistochemistry was performed on the same specimen after making paraffin blocks to study p16 overexpression. STATISTICAL ANALYSIS USED: Chi-square test was used to analyze the differences between discrete variables. RESULTS: 5/6 (83.3%) HPV-DNA-positive cases were positive for p16 expression, whereas 26/44 (59.09%) p16-positive cases which were negative for HPV-DNA. Sensitivity and specificity of p16 as a surrogate marker for HPV-DNA were found to be 83.3% and 40%, respectively. CONCLUSIONS: p16 immunostaining is a good first-line assay for eliminating HPV-negative cases from additional analysis, but other causes of p16 overexpression in oral tumorigenesis related to tobacco consumption in keratinizing squamous cell carcinoma needs to be explored further.

Chronic Auditory Toxicity in Late Preterm and Term Infants With Significant Hyperbilirubinemia.

BACKGROUND AND OBJECTIVES: Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spectrum disorder and/or sensorineural hearing loss); however, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. Our objective was to compare TSB, bilirubin albumin molar ratio (BAMR), and unbound bilirubin (UB) for their association with chronic auditory toxicity in neonates with SHB (TSB ≥20 mg/dL or TSB that met criteria for exchange transfusion). METHODS: Infants ≥34 weeks' gestational age (GA) with SHB during the first 2 postnatal weeks were eligible for a prospective longitudinal study in India. Comprehensive auditory evaluations were performed at 2 to 3 months of age by using auditory brainstem response, tympanometry, and an otoacoustic emission test and at 9 to 12 months of age by using audiometry. The evaluations were performed by an audiologist unaware of the degree of jaundice. RESULTS: A total of 93 out of 100 infants (mean GA of 37.4 weeks; 55 boys, 38 girls) who were enrolled with SHB were evaluated for auditory toxicity. Of those, 12 infants (13%) had auditory toxicity. On regression analysis controlling for covariates, peak UB (but not peak TSB or peak BAMR), was associated with auditory toxicity (odds ratio 2.41; 95% confidence interval: 1.43-4.07; P = .001). There was significant difference in the area under the receiver operating characteristic curves between UB (0.866), TSB (0.775), and BAMR (0.724) for auditory toxicity (P = .03) after controlling for covariates. CONCLUSIONS: Unconjugated hyperbilirubinemia indexed by UB (but not TSB or BAMR) is associated with chronic auditory toxicity in infants ≥34 weeks' GA with SHB.

Effective Screening and Classification of Cervical Precancer Biopsy Imagery.

Microscope images of biopsy samples of cervical precancers conventionally discriminated by histopathology, the current "gold standard" for cancer detection, showed that their correlation properties are segregated into different classes. The correlation domains clearly indicate increasing cellular clustering in different grades of precancer compared with their normal counterparts. This trend indicates the probability of pixel distribution of the corresponding tissue images. Because the cell density is not uniform in the higher grades, the skewness (asymmetry of a distribution), kurtosis (sharpness of a distribution), entropy (randomness), and standard deviation are affected. A combination of these parameters effectively improves the diagnosis and quantitatively classifies the normal and all the three grades of precancerous cervical tissue sections significantly. Thus, the statistical analysis of microscope images is a promising approach for early stage tumor detection and quantitative classification of precancerous grades; this can effectively supplement the qualitative analysis by the pathologist.

Errors, limitations, and pitfalls in the diagnosis of central and peripheral nervous system lesions in intraoperative cytology and frozen sections.

CONTEXT: Intraoperative cytology and frozen section play an important role in the diagnosis of neurosurgical specimens. There are limitations in both these procedures but understanding the errors and pitfalls may help in increasing the diagnostic yield. AIMS: To find the diagnostic accuracy of intraoperative cytology and frozen section for central and peripheral nervous system (PNS) lesions and analyze the errors, pitfalls, and limitations in these procedures. SETTINGS AND DESIGN: Eighty cases were included in this prospective study in a span of 1.5 years. MATERIALS AND METHODS: The crush preparations and the frozen sections were stained with hematoxylin and eosin method. The diagnosis of crush smears and the frozen sections were compared with the diagnosis in the paraffin section, which was considered as the gold standard. STATISTICAL ANALYSES USED: Diagnostic accuracy, sensitivity, and specificity. RESULTS: The diagnostic accuracy of crush smears was 91.25% with a sensitivity of 95.5% and specificity of 100%. In the frozen sections, the overall diagnostic accuracy was 95%, sensitivity was 96.8%, and specificity was 100%. The categories of pitfalls noted in this study were categorization of spindle cell lesions, differentiation of oligodendroglioma from astrocytoma in frozen sections, differentiation of coagulative tumor necrosis of glioblastoma multiforme (GBM) from the caseous necrosis of tuberculosis, grading of gliomas in frozen section, and differentiation of the normal granular cells of the cerebellum from the lymphocytes in cytological smears. CONCLUSIONS: Crush smear and frozen section are complimentary procedures. When both are used together, the diagnostic yield is substantially increased.

Wavelet-based characterization of spectral fluctuations in normal, benign, and cancerous human breast tissues.

Fluorescence intensity fluctuations in the visible wavelength regime in normal, benign, and cancerous human breast tissue samples are studied through wavelet transform. The analyses have been carried out in unpolarized, parallel and perpendicularly polarized channels, for optimal tissue characterization. It has been observed that polarized fluorescence data, particularly the perpendicular components, differentiate various tissue types quite well. Wavelet transform, because of its ability for multiresolution analysis, provides the ideal tool to separate and characterize fluctuations in the fluorescence spectra at different scales. We quantify these differences and find that the fluctuations in the perpendicular channel of the cancerous tissues are more randomized as compared to their normal counterparts. Furthermore, for cancerous tissues, the same is very well described by the normal distribution, which is not the case for normal and benign samples. It has also been observed that, up to a certain point, fluctuations at larger scales are more sensitive to tissue types. The differences in the average, low-pass wavelet coefficients of normal, cancerous, pericanalicular, and intracanalicular benign tissues are also pointed out.

Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants.

BACKGROUND: In utero latent iron deficiency has been associated with abnormal neurodevelopmental outcomes during childhood. Its concomitant effect on auditory neural maturation has not been well studied in late preterm and term infants. OBJECTIVE: The objective was to determine whether in utero iron status is associated with auditory neural maturation in late preterm and term infants. DESIGN: This prospective cohort study was performed at Sir Ganga Ram Hospital, New Delhi, India. Infants with a gestational age ≥34 wk were eligible unless they met the exclusion criteria: craniofacial anomalies, chromosomal disorders, hemolytic disease, multiple gestation, third-trimester maternal infection, chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus infections (TORCH), Apgar score <5 at 5 min, sepsis, cord blood not collected, or auditory evaluation unable to be performed. Sixty consecutive infants with risk factors for iron deficiency, such as small for gestational age and maternal diabetes, and 30 without risk factors for iron deficiency were enrolled. Absolute wave latencies and interpeak latencies, evaluated by auditory brainstem response within 48 h after birth, were measured and compared between infants with latent iron deficiency (serum ferritin ≤75 ng/mL) and infants with normal iron status (serum ferritin >75 ng/mL) at birth. RESULTS: Twenty-three infants had latent iron deficiency. Infants with latent iron deficiency had significantly prolonged wave V latencies (7.10 ± 0.68 compared with 6.60 ± 0.66), III-V interpeak latencies (2.37 ± 0.64 compared with 2.07 ± 0.33), and I-V interpeak latencies (5.10 ± 0.57 compared with 4.72 ± 0.56) compared with infants with normal iron status (P < 0.05). This difference remained significant on regression analyses after control for confounders. No difference was noted between latencies I and III and interpeak latencies I-III. CONCLUSION: Latent iron deficiency is associated with abnormal auditory neural maturation in infants at ≥34 wk gestational age. This trial was registered at clinicaltrials.gov as NCT02503397.

Effect of sulphur dioxide inhalation on serum Na and K+ ion concentration in albino rat.

A study was carried out to assess the effect of 60 ppm and 120 ppm exposure of sulphur dioxide gas for one hour daily for 2 and 4 week on serum sodium(Na+) and potassium (K+) ion concentration in albino rat, Rattus norvegicus (Berkenhout). The present findings reveal that serum sodium (Na+) ion concentration increased significantly after 4 week exposure to 120 ppm of sulphur dioxide, while serum potassium ion (K+) concentration decreased significantly after 4 week exposure to 120 ppm of sulphur dioxide.

Cytomorphological features of lymphoepithelial carcinoma of submandibular gland in an adolescent male.

A case of lymphoepithelial carcinoma (LEC) occurring in right submandibular gland of a 13-year-old Indian male is presented, wherein the lesion unveiled itself only after multiple fine needle aspiration (FNA) procedures. This unusual neoplasm has high frequency of occurrence in Eskimos and a predilection for the parotid gland. The aspirates obtained were highly cellular comprising tight clusters of atypical epithelial cells with admixture of lymphocytes. Histopathological examination of the resected submandibular gland and lymph node chain was consistent with the diagnosis of LEC. Immunohistochemistry (IHC) revealed cytokeratin (CK)-positive and S-100-negative tumor cells lying admixed with CD45-positive lymphoid cells. A detailed otorhinolaryngological examination with inclusion of multiple biopsies was found negative for any primary tumor. Although histopathological features of this entity are well established, only a handful of case reports describing cytological features of this entity are present in medical literature. We conclude that the cytomorphological features of LEC are sufficiently distinctive to at least, suggest a possibility of this lesion.

Microfilaria in cytological smears at rare sites coexisting with unusual pathology: A series of seven cases.

Filariasis is a major public health problem in India and microfilaria is sometimes seen during routine fine needle aspiration cytology (FNAC) smears, but it is very rare to find microfilaria coexistent with neoplastic lesions. Here we report a series of seven cases in which microfilaria is associated with neoplastic lesions. Out of these seven cases one is benign and six are malignant. Also we first time report the microfilaria coexistent with parotid pleomorphic adenoma, undifferentiated carcinoma thyroid and gall bladder carcinoma.

Tonsillar follicular lymphoma in a child.

Follicular lymphomas (FL) are among the most common non-Hodgkin's lymphoma (NHL) in adults. However, they are rare in children making up less than 3% of paediatric NHL cases. They occur most commonly in the head and neck region, lymph nodes or tonsils, with occasional extra-nodal occurrences. Distinction of FL from potentially clonal but, reactive follicular hyperplasia is important. We report a case of a 6-year-old male child presenting with night stridor since 6 months. Clinical examination revealed asymmetrical enlargement of the left tonsil. Routine left tonsillectomy was performed and the specimen was sent for histopathological examination. Diagnosis of follicular lymphoma was made on histopathological examination and further confirmed by immunohistochemistry.

Primary orbital non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) can have extra-nodal presentation in approximately 25% of cases unlike Hodgkin's lymphoma which rarely involves extra-nodal sites. Extra-nodal lymphoma in the head and neck region is extremely rare. We report a case of 6-year-old girl who presented with medial canthus mass with proptosis, lagophthalmos and no significant loss of vision. CT findings showed an extra-conal homogenous mass lesion in the left orbit along superior and medial orbital wall with extensive destruction of surrounding tissue. Histological sections showed polymorphous population of atypical lymphoid cells accompanied by plasma cells, eosinophils and proliferation of small blood vessels with plump endothelial cells. A diagnosis of NHL was rendered. Further, immunohistochemistry confirmed the lesion as peripheral T-cell lymphoma. The lesion was aggressive in course and the patient succumbed within one-and-half months of diagnosis.

Recurrent hyperphosphatemic tumoural calcinosis.

Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur in a variety of clinical settings, characterised by subcutaneous deposition of calcium phosphate with or without giant cell reaction. We describe a case of 11-year-old girl presenting with recurrent hard swellings in the vicinity of shoulder and hip joints associated with elevated serum phosphate and normal serum calcium levels. TC has been mainly reported from Africa, with very few cases reported from India. After the diagnosis of hyperphosphatemic TC was established, the patient was treated with oral sevelamer and is under constant follow-up to detect recurrence, if any. The present case highlights the fact that although an uncommon lesion, TC must be considered in the differential diagnosis of subcutaneous hard lump in the vicinity of a joint.

Fluorescence spectroscopy: a new approach in cervical cancer.

OBJECTIVE: To study the diagnostic potential of fluorescence spectroscopy and its comparison with different screening methods, including Pap smear and colposcopy, in detecting early cervical neoplasia. METHOD: The study was conducted on patients with gynecological complaints. A full gynecological workup of the patients was done along with Pap smear and colposcopy. Cervical biopsy was done in suspected cases and fresh tissue was sent to IIT for spectroscopy. RESULT: There is a definite increase in NADH fluorescence (67.4 %) and a decrease in collagen fluorescence (74 %) in dysplastic tissues. When epithelial fluorescence and stromal fluorescence are considered together, diagnostic accuracy is increased to 96.5 %. CONCLUSION: The clinical diagnosis of cervical neoplasia by spectroscopic methods is potentially a reliable, fast, and cost-effective alternative to the conventional smear test which needs trained personnel for its interpretation. Research is still continuing to obtain a statistically significant cutoff value from in vitro studies and then use them for in vivo study.

Expression and clinicopathological significance of estrogen and progesterone receptors in gallbladder cancer.

BACKGROUND: Clinical significance of sex hormone receptors in gallbladder cancer is not yet established. This study was performed to assess the expression pattern of estrogen and progesterone receptors in benign and malignant gallbladder lesions, and to assess their clinicopathological significance. METHODS: Tissue samples from resected gallbladder for cholelithiasis (n = 20) and carcinoma gallbladder (n = 25) were evaluated for estrogen and progesterone receptor (ER, PR) expression by automated immunohistochemistry. Their expression was correlated with different clinicopathological parameters. RESULTS: ER expression was significantly high (28%, 95% confidence interval [CI], 14-47) in gallbladder cancer than in chronic cholecystitis (0%; P = .012). PR expression did not differ in two groups (benign 40%, 95% CI, 21.8-61.4; malignant 52%, 95% CI, 33.5-69.9). Metaplastic benign lesions had near significant higher expression of PR (71.4%) than nonmetaplastic lesion (15.9%; P = .062). Their expression did not correlate with gender, age, menopausal status, presence of gallstones, tumor differentiation, and tumor stage. CONCLUSION: Female sex hormones play an important role in the gallbladder carcinogenesis. ER and PR may not have prognostic value. Presence of ER in ∼1/3 and PR in 1/2 of patients with carcinoma gallbladder suggests the potential role of antihormonal therapy.

Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular involvement.

Rosai-Dorfman disease, that is, sinus histiocytosis with massive lymphadenopathy is a benign systemic proliferative disorder of histiocytes. The typical clinical presentation of the disease includes bilateral painless massive lymphadenopathy, fever and polyclonal hypergammaglobulinemia. Extranodal involvement is present in only a few cases and skin lesions are the most common form of extranodal disease. However, purely cutaneous Rosai-Dorfman disease is uncommon. In this study, we describe a 10-year-old child presenting with bilateral ocular involvement.