Role of CD44 as cancer stem cell marker in triple-negative breast cancer and its association with histological grade and angiogenesis

Introduction: Cancer stem cells (CSC) within the tumors play a central role in tumorigenesis. It is, thus, of utmost importance to identify these cells to develop effective cancer therapy. Triple-Negative Breast Cancer (TNBC) is an aggressive molecular subtype of breast cancer associated with poor patient outcomes. The role of CD44 immunohistochemistry (IHC) as a putative CSC in breast carcinomas, particularly of the TNBC-subtype is ambiguous, with equivocal results. Aims and Objectives: The present study aims to assess the role of CSC in breast carcinoma by immunohistochemical analysis of CD44 expression in TNBC. The association of TNBC expressing CSC with histological grade as well as with angiogenesis (using CD34 IHC) has been studied. Materials and Methods: Biopsy samples from 58 patients with infiltrating ductal carcinoma, NST were studied. The histology of the tumor was sub-classified into grades 1–3. Based on immunohistochemical analysis (ER, PR, HER2/Neu), the cases were divided into TNBC and NTNBC groups. The tissue sections were also subjected to analysis for CD44 to identify the CSC-phenotype and CD34 to evaluate angiogenesis, to determine the microvascular density (MVD). Results: Out of the 58 cases in the study, 28 were TNBC and 30 were NTNBC. CSC phenotype (CD44 positive) was expressed significantly higher in the TNBC (78%) versus the NTNBC (53%) (p-value 0.043). The MVD estimated using CD34 IHC was lower in the TNBC group in our study, though the difference was not statistically significant. A larger proportion of cases in TNBC showed a higher histological grade (35%) in comparison to NTNBC (27%). However, statistically, it was not significant. Conclusion: Our study demonstrated that CD44 as a CSC marker is seen significantly more in the TNBC category of invasive ductal carcinomas. Further large-scale studies, to confirm these findings, will be of potential therapeutic and prognostic value.

Anaplasia in childhood rhabdomyosarcoma: An under reported entity

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Anaplasia is a rare phenomenon seen in childhood RMS. The most common histologic subtype was Embryonal followed by Alveolar and spindle subtype. Design: A total of 11 cases of pediatric RMS were selected from January 2017 to June 2019 presenting at various sites. Out of 11 cases, 2 were further diagnosed as Embryonal, 2 as Alveolar, 2 as Pleomorphic, 1 as Spindle subtype and rest 4 as RMS-NOS based on morphology. All cases were positive for Desmin. The presence of cells with lobated, hyperchromatic nuclei at least three times larger than the tumor cell (anaplastic cells) was selected as the main criterion to diagnose Anaplasia. Results: Out of the total 11 cases, anaplasia was seen in 7 cases. Out of these seven, five cases showed Focal Anaplasia (FA) (71.4%) and 2 cases showed Diffuse Anaplasia (DA) (28.6%). Out of 2 cases of Embryonal RMS one exhibited focal anaplasia (50%). One case of Spindle RMS showed diffuse anaplasia, 2 cases of pleomorphic RMS showed focal anaplasia. Out of 3 cases of RMS- NOS, 2 exhibited focal anaplaisa and one displayed Diffuse anaplasia. Both Alveolar RMS had no features of anaplasia. Conclusion: Presence of Anaplasia is a frequent observation in pediatric RMS. Anaplasia is often under reported in pediatric RMS. Pathologist should be more aware of this rare phenomenon.

Extensive oral telangiectasias in systemic sclerosis

The word telangiectasia is derived from tel- end, angos- vessels and ectasis- dilatation. Telangiectasia can be primary orsecondary. Connective tissue diseases like systemic sclerosis, dermatomyositis and systemic lupus erythematosus maybe associated with secondary telangiectasias. Systemic sclerosis presents with mat-like telangiectasias over face, handsand rarely oral mucosa. The present study discusses a case of extensive oral telangiectasias without significant sclerosisover face.

The impact of primary open-angle glaucoma: Comparison of vision-specific (National Eye Institute Visual Function Questionnaire-25) and disease-specific (Glaucoma Quality of Life-15 and Viswanathan 10) patient-reported outcome (PRO) instruments

Purpose: To compare a general vision-specific patient-reported outcomes (PRO) instrument, National Eye Institute Visual Function Questionnaire-25 (NEIVFQ-25) with two disease-specific PRO instruments, Glaucoma Quality of Life-15 (GQL-15), and Viswanathan 10 in patients with varying severity of primary open angle glaucoma (POAG). Methods: This hospital-based, prospective study enrolled 140 glaucoma patients. The patients were classified into mild, moderate, and severe glaucoma based on visual field defects. All these patients were administered the three PRO instruments and the results were statistically analyzed. Results: All the three instruments showed high internal consistency (Cronbach's alpha for GQL-15, NEIVFQ-25, and Viswanathan 10 were 0.918, 0.937, and 0.929, respectively) There was a statistically significant difference between patients with mild, moderate, and severe POAG with all instruments (P ? 0.001). The instruments correlated well across several parameters especially the peripheral vision and glare/dark adaptation. The disease-specific scales however are simpler and faster to administer. Conclusion: All three instruments were reliable in assessment of mild, moderate, and severe glaucoma. They correlated strongly with each other in most of the related subscales, domains, and questions. NEIVFQ-25 additionally gave information regarding the general, psychological, and social effects of the disease.

The impact of primary open-angle glaucoma: Quality of life in Indian patients

Purpose: Glaucoma significantly affects the quality of life (QoL) of a patient. Despite the huge number of glaucoma patients in India, not many, QoL studies have been carried out. The purpose of the present study was to evaluate the QoL in Indian patients with varying severity of glaucoma. Methods: This was a hospital-based, cross-sectional, analytical study of 180 patients. The QoL was assessed using orally administered QoL instruments comprising of two glaucoma-specific instruments; Glaucoma Quality of Life-15 (GQL-15) and Viswanathan 10 instrument, and 1 vision-specific instrument; National Eye Institute Visual Function Questionnaire-25 (NEIVFQ25). Results: Using NEIVFQ25, the difference between mean QoL scores among cases (88.34 ± 4.53) and controls (95.32 ± 5.76) was statistically significant. In GQL-15, there was a statistically significant difference between mean scores of cases (22.58 ± 5.23) and controls (16.52 ± 1.24). The difference in mean scores with Viswanathan 10 instrument in cases (7.92 ± 0.54) and controls (9.475 ± 0.505) was also statistically significant. QoL scores also showed moderate correlation with mean deviation, pattern standard deviation, and vertical cup-disc ratio. Conclusion: In our study, all the three instruments showed decrease in QoL in glaucoma patients compared to controls. With the increase in severity of glaucoma, corresponding decrease in QoL was observed. It is important for ophthalmologists to understand about the QoL in glaucoma patients so as to have a more holistic approach to patients and for effective delivery of treatment.

Bacteriological profile and antibiotic sensitivity pattern of neonatal septicaemia in a rural tertiary care hospital in North India.

Background: There is not much published literature on neonatal septicemia available for the Sub‑Himalayan region of North India. Hence, we undertook this study to find out the bacteriological profile and antibiotic sensitivity pattern of neonatal septicemia in the neonatal Intensive Care Unit. Material and Methods: Blood cultures were performed for all clinically suspected neonatal septicemia cases for 1‑year. Identification of all pathogenic isolates was followed by antibiotic sensitivity testing. Results: We did blood cultures for 450 neonates and 42% were culture positive. Early onset sepsis were 92 (49%) and 96 (51%) were late onset sepsis. Gram‑positive isolates were 60% and 40% were Gram‑negative. Staphylococcus aureus (40%), coagulase negative Staphylococcus species (16%), non‑fermenter group of organisms (NFGOs) (15%), and Klebsiella pneumoniae (10%) were the main isolates. Nasal cannula 101 (54%), birth asphyxia 91 (48%), and prematurity 73 (38%) were the prominent risk factors associated with septicemia. Gram‑positive organisms were highly resistant to penicillin (87%) whereas Gram‑negative isolates showed high resistance to third generation cephalosporins (53–89%) and aminoglycosides (50–67%). The S. aureus isolates were methicillin‑resistant in 41% whereas extended spectrum beta lactamase production was seen in 48% Gram‑negative isolates. Conclusion: Our study highlights the recent emergence of Gram‑positive organisms as predominant cause of neonatal septicemia in this part of Sub‑Himalayan region, along with the review of literature which shows similar results from North India and rest of the world too. Though Gram‑negative bacteria still remain the main cause of mortality in neonatal septicemia, we want to dispel the common notion among practitioners that they are the predominant isolates in neonatal septicemia.

Isolation of Brucella melitensis from a human case of chronic additive polyarthritis.

Brucellar arthritis remains under diagnosed owing to non‑specific clinical manifestations. Here, we report isolation of Brucella melitensis from synovial fluid of 5th metatarsophalangeal joint of a 39‑year‑old lady having unusually chronic asymmetric, additive, peripheral polyarthritis. This isolation was confirmed by Bruce‑Ladder polymerase chain reaction (PCR). The patient had a history of contact with an aborted goat. Rose Bengal Plate Agglutination Test (RBPT) and Standard Tube Agglutination Test (SAT) were positive for Brucella‑specific antibodies both for patient and in contact with sheep and goats. The patient was treated with doxycycline and rifampicin for 16 weeks and was recovered fully.

Ascariasis as a cause of hepatic abscess: A report of 3 cases.

We receive around 60 cases of hepatic abscess in a year. The commonest diagnosis reached at the time of discharge is amoebic liver abscess. The diagnosis of amoebic liver abscess is mostly presumptive and thus the patients are usually given a mixed treatment with injection ceftriaxone and tablet metronidazole. Here we report three cases of hepatic abscess diagnosed recently, where ascariasis was the probable etiology. Ascariasis may be a much commoner cause of hepatic abscesses in this region than we think.

Detection of flea‑borne Rickettsia species in the Western Himalayan region of India.

Human infections by various rickettsial species are frequently reported globally. We investigated a flea‑borne rickettsial outbreak infecting 300 people in Western Himalayan region of India. Arthropod vectors (ticks and fleas) and animal and human blood samples from affected households were analysed by gltA and ompB genes based polymerase chain reaction (PCR). Rat flea (Ceratophyllus fasciatus) samples were found harbouring a Rickettsia sp. Phylogenetic analysis based on gltA gene using PHYLIP revealed that the detected Rickettsia sp. has 100% identity with SE313 and RF2125 strains of Rickettsia sp. of flea origin from Egypt and Thai‑Myanmar border, respectively and cf1 and 5 strains from fleas and lice from the USA. But, the nucleotide sequence of genetically variable gene ompB of R14 strain was found closely related to cf9 strain, reported from Ctenocephalides felis fleas. These results highlight the public health importance of such newly discovered or less recognised Rickettsia species/strains, harboured by arthropod vectors like fleas.

Assessment of Health-Related Quality of Life in school-going adolescents: Validation of PedsQL instrument and comparison with WHOQOL-BREF

Background. Health-Related Quality of Life (HRQoL) studies are gaining importance. Yet there is a dearth of crossculturally validated generic HRQoL instruments for Indian adolescents. Two HRQoL instruments, namely World Health Organization Quality of Life-Brief (WHOQOL-BREF) and Pediatric Quality of Life inventoryTM 4.0 (PedsQL), are widely used internationally, with both measuring four domains (physical, psychological/emotional, social relations and environment/school) but each having different questions with 26 in the former and 23 in the latter. This study was done among adolescents in the city of Lucknow to evaluate the psychometric properties of PedsQL and compare its performance with previously validated and culturally revised WHOQOL-BREF. Methods. This cross-sectional study was conducted in February 2010 after institutional ethical approval. Data were collected by a self-administered, predesigned questionnaire in which items of PedsQL and revised WHOQOL-BREF were intermingled. Reliability, content and construct validity were evaluated for PedsQL. Convergent validity of PedsQL with revised WHOQOL-BREF was calculated for domains with similar questions. Results. Parents of 76.5% adolescents (385/503) provided consent. Mean age of adolescents was 13.6 years (1.6 SD and 44.7% were girls). PedsQL showed substantial reliability (Cronbach alpha=0.82, p<0.00001) but poor to fair validity as compared to revised WHOQOL-BREF. Conclusions. For Indian adolescents, PedsQL is a reliable and valid instrument. However, on comparison with revised WHOQOL-BREF, PedsQL has poor to fair validity. We conclude that revised WHOQOL-BREF is a better HRQoL instrument for Indian adolescents.

Acute Renal Failure and Seizure following Multiple Wasp Stings: A Case Report.

Wasps and bees descend from order Hymenoptera. All social wasps belong to family Vespidae. Their stings are not usually life threatening, causing mainly local reactions and rarely anaphylaxis and serious systemic manifestations. Though a few stings cause no major problems, multiple stings can cause serious effects like massive hemolysis, acute renal failure, encephalopathy, multiorgan dysfunction. We report a six years boy with acute renal failure and seizure following multiple wasp stings.

Emerging Salmonella Paratyphi A enteric fever and changing trends in antimicrobial resistance pattern of salmonella in Shimla.

This retrospective study incorporates a six years, six months (January 2000-June 2006) laboratory data comprising 258 isolates of Salmonella. Cultures were identified by standard methods. Salmonella enterica serotype Typhi (S.Typhi) was the more frequent serotype isolated i.e., 61.62% with the remaining 38.37% being Salmonella enterica serotype Paratyphi A (S. Paratyphi A). There was emergence of S. Paratyphi A as the predominant serotype in 2003-2004 with resurgence of serotype Typhi thereon. A total of 66.27% isolates were resistant to one or more antibiotics. MDR S. Typhi was 10.69% and while 13.13% were MDR S. Paratyphi A. There was decrease in resistance to ampicillin, cotrimoxazole in 2004 and nalidixic acid beyond 2005 and increase in resistance to cefuroxime. We also documented a decrease in resistance to ciprofloxacin after 2005.

Congenital CMV infection; diagnosis in symptomatic infants.

Background: Samples from babies exhibiting clinical symptoms suggestive of congenital infection are referred regularly to NICD, New Delhi,, from Government Hospitals located in Delhi and a home for abandoned children (Palna), for the diagnosis of etiological agents like toxoplasma, rubella, CMV and herpes. Blood samples of mothers of most of the affected babies are also received. Objective: Evaluation of rapid and accurate technique for the diagnosis of congenital CMV infection. Materials and Methods: One hundred and twenty five blood samples suggestive of symptomatic congenital CMV infection were selected from samples received at NICD during the period June 2005-March 2007. A request to collect and send the urine samples of the selected babies was sent to the respective hospitals. Serum samples of the babies were tested for CMV-IgM antibodies using µ-capture ELISA. Mothers' serum samples were subjected to CMV-IgM and IgG class antibodies assay by commercial ELISA kits. DNA isolation and amplification was performed in urine samples and some of the serum samples using a commercial PCR kit for detection of HCMV. Blood and urine samples from 20 normal babies were included in the study. Results: Twenty Seven serum samples (21.6%) of infants, of the 125 tested, were positive for CMV-IgM antibodies. Twenty five samples (20%) showed amplification of CMV -DNA. All 25 samples positive for PCR were positive for CMV IgM antibodies. Sera of 73 mothers, out of 75 tested (97.3%), were positive for CMV IgG antibodies. However, none of them was positive for CMV IgM antibodies. Mothers of all 27 positive babies were positive for CMV-IgG antibodies. Serum and urine samples from 20 normal babies were negative for ELISA and PCR. Conclusion: µ-capture ELISA technique was found to be more sensitive than PCR (92.6%) for detection of congenital CMV infection. ELISA is also rapid, less cumbersome and cost effective for diagnosis of CMV infection.

Rabies: control strategies for Himalayan states of the Indian subcontinent.

Rabies remains to be one of the most important direct zoonosis and is invariably fatal once the clinical symptoms appear. The disease can be prevented but still people continue to die of infection. India alone accounts to 81 per cent of the total deaths occurring due to rabies across the world. Dog is major reservoir of the infection, although other domestic and wild reservoirs also play an important role in the spread of the disease. A large population of stray dogs, availability of susceptible hosts, close proximity of animals and man and lack of effective control strategies might have led to endemic status of the disease in India. The effective control of rabies can be achieved through reduction of the stray dogs and stray livestock populations through implementation of animal birth control (ABC) programme and the proper induction of "herd immunity" by mass vaccination and awareness health programme. The increase in human population, changes in the environment, increased transportation, development of human habitations in new places and seasonal migration of the animals have resulted in the introduction of the infection to new territories and changes in the epidemiology of the disease in hills. Therefore, it is essential to design area specific control programmes so that the disease can be eliminated effectively.

Enalaprilat induced acute parotitis.

Drug induced acute parotitis is a very uncommon complication reported with a few drugs only. There is no case of acute bilateral parotitis reported previously with i.v. enalaprilat. We present here a female patient who developed acute bilateral parotitis within minutes of i.v. enalaprilat injection and recovered within 24 hours of stopping the drug and with symptomatic treatment.

Prevalence of glaucoma in Sunsari district of eastern Nepal.

AIMS: To determine prevalence of glaucoma and glaucoma suspect in subjects 40 years and above in Sunsari district of eastern Nepal. METHODS: A community based cross sectional study examining 1600 selected subjects was carried out. In all subjects best corrected visual acuity was determined. Oblique torch light test was used for anterior chamber depth evaluation. Intraocular pressure (IOP) measurements with Perkins tonometer and fundus examination were carried out in the community. Subjects diagnosed as glaucoma suspect were further evaluated in the hospital using slit lamp examination, gonioscopy and Goldmann perimetry. Glaucoma was defined by characteristic disc and visual field changes irrespective of the level of IOP. RESULTS: Of 1600 subjects examined, the prevalence of glaucoma was found to be 0.938%. The prevalences of primary open angle glaucoma, primary angle closure glaucoma, secondary glaucoma and ocular hypertension were 0.562%, 0.125%, 0.250% and 0.500% respectively. Lens induced glaucoma accounted for all the cases of secondary glaucoma. CONCLUSION: The prevalence of glaucoma in the Sunsari District of Nepal is 0.938%, which is lower than that reported in the neighboring regions. Lens induced glaucoma is highly prevalent as a cause of secondary glaucoma.

Pharmacovigilance in kala-azar patients with severe thrombocytopenia caused by sodium antimony gluconate & miltefosine.

Sodium antimony gluconate (SAG) and miltefosine used in the treatment of kala-azar are known to cause several side effects but severe thrombocytopenia has not been reported. Four cases of severe thrombocytopenia, two caused by SAG and two by miltefosine were promptly detected and treated by immediate withdrawal of the offending drugs, platelet and blood transfusions and dexamethasone. After improvement Leishman-Donovan (LD) bodies were demonstrated in splenic aspirates of both patients of SAG group and one of miltefosine and they were treated with 1 mg/kg body wt of amphotericin B for 20 days and cured. One patient of miltefosine group treated outside only on the basis of rK-39 positivity did not show LD bodies in splenic aspirates and improved without any antikala- azar drug. None of the patients relapsed within 6 months of follow up. Prompt detection of side effects under the concept of pharmacovigilance can save life of such patients.