Vitiligo: Correlation with Cytokine Profiles and its Role in Novel Therapeutic Strategies: A Case-Control Study.

Background: The inflammatory and immune factors play a key role in the pathogenesis of vitiligo, and there are very few studies that have investigated the levels of major cytokines produced by T helper (Th) 1, Th2, and Th17 cells. This can enable better understanding of the, pathogenesis, and severity of vitiligo. Objectives: To evaluate the serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1ß, interferon (IFN)-γ, and IL-10 in patients with vitiligo and to correlate them with the disease severity and activity and to compare them with normal healthy controls. Materials and Methods: A case-control study was conducted with 100 study participants: 50 cases clinically diagnosed as vitiligo and 50 controls. All patients underwent complete evaluation with detailed demographic parameters, history, and physical examination. The severity of the disease was assessed clinically by Vitiligo Area Scoring Index (VASI) and Vitiligo Disease Activity Score (VIDA). Blood investigations performed were IL-6, TNF-α, IL-1ß, IFN-γ, and IL-10. Results: We observed significantly higher levels of serum IFN-γ levels in the patient group when compared with those of the normal controls (P = 0.002) and showed a positive correlation with the activity and severity of the disease with a significant VASI (P = 0.05) and VIDA score (P = < 0.001). The mean serum IL-10 (p < 0.001) in patients with vitiligo was significantly lower than that in the control group. There was no significant difference in the serum level of TNF-α level (P = 0.347), IL-6 (P = 0.365), and IL-1ß (P = 0.362) between vitiligo and healthy controls. Conclusion: This study proved that high serum level of IFN-γ may be a risk factor for vitiligo progression and significantly low levels of IL-10, which has an anti-inflammatory role, suggesting that they could be used as a marker for assessing vitiligo activity and may open the way for further therapeutic approaches for vitiligo.

Evaluation of Alteration in Oral Microbial Flora Pre- and Postradiation Therapy in Patients with Head and Neck Cancer.

INTRODUCTION: For decades now, head and neck cancer (HNC) remains to be one of the deadliest; per se the treatment for the same has been evolving for the past years. Radiation therapy (RT) has been one among the various treatment modalities adopted to treat HNC. The fact that RT can affect the quality of life in these patients cannot be denied. In patients with HNC, these can bring about a wide array of lesions in oral cavity and its associated structures as these areas are invariably affected due to exposure to radiation as such. These include alteration in salivary parameters, changes in microbial flora, and occurrence of radiation caries. AIM: In our study we aimed at assessing the alteration in oral microbial flora inclusive of Streptococcus mutans and Lactobacillus colony count before and after RT. MATERIALS AND METHODS: Saliva and plaque samples were collected from patients with HNC, who were prescribed to undergo intensity-modulated radiation therapy (IMRT) amounting to a mean radiation dosage of 60 Gy units. The aforementioned samples were collected at three different intervals, before, immediately after, and 6 months after RT. The samples were cultured in selective media in three different dilutions (1:10, 1:100, and 1:1000). Following with colony counting is carried out using a standardized colony counter. CONCLUSION: The results showed a significant alteration in microbial flora pre- and post-RT. Individual parameters do not show a single stand in causing these changes. Moreover, these changes seem to have earned a multifactorial contribution.

Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19).

Coronavirus has emerged as a global health threat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge.

Socio-economic & demographic determinants of hypertension & knowledge, practices & risk behaviour of tribals in India.

BACKGROUND & OBJECTIVES: An increase in prevalence of hypertension has been observed in all ethnic groups in India. The objective of the present study was to estimate prevalence and determinants of hypertension among tribals and their awareness, treatment practices and risk behaviours in nine States of India. METHODS: A community based cross-sectional study adopting multistage random sampling procedure was carried out. About 120 Integrated Tribal Development Authority villages were selected randomly from each State. From each village, 40 households were covered randomly. All men and women ≥ 20 yr of age in the selected households were included for various investigations. RESULTS: A total of 21141 men and 26260 women participated in the study. The prevalence of hypertension after age adjustment was 27.1 and 26.4 per cent among men and women, respectively. It was higher in the s0 tates of Odisha (50-54.4%) and Kerala (36.7-45%) and lowest in Gujarat (7-11.5%). The risk of hypertension was 6-8 times higher in elderly people and 2-3 times in 35-59 yr compared with 20-34 yr. Only <10 per cent of men and women were known hypertensives and more than half on treatment (55-68%). Men with general and abdominal obesity were at 1.69 (CI: 1.43-2.01) and 2.42 (CI: 2.01-2.91) times higher risk of hypertension, respectively, while it was 2.03 (CI=1.77-2.33) and 2.35 (CI 2.12-2.60) times higher in women. Those using tobacco and consuming alcohol were at a higher risk of hypertension compared with the non users. INTERPRETATION & CONCLUSIONS: The study revealed high prevalence of hypertension among tribals in India. Age, literacy, physical activity, consumption of tobacco, alcohol and obesity were significantly associated with hypertension. Awareness and knowledge about hypertension and health seeking behaviour were low. Appropriate intervention strategies need to be adopted to increase awareness and treatment practices of hypertension among tribals.

Mid-term outcomes of self-expanding covered stent grafts for repair of popliteal artery aneurysms.

BACKGROUND: Enthusiasm for endovascular therapies has led to the use of stent graft repairs for popliteal artery aneurysms. In this report, we review our experience with this technique. METHODS: A retrospective review was performed of all endovascular popliteal artery aneurysm repairs (EVPARs) performed by the vascular surgery group at a tertiary care medical center. Patient demographic data, operative details, and outcomes were examined. RESULTS: We performed 33 EVPARs in 28 patients. All patients were male with a mean age of 76 years (range, 60-91). Mean aneurysm diameter was 3.2 cm (range, 1.5-6.3). All repairs were performed using a self-expanding covered stent graft. Among the patients, 18% were symptomatic at the time of repair. The median number of stents used was 2 (range, 1-4). Median duration of stay was 1 day (range, 0-12). The 1-year and 2-year patency were 87% and 81%, respectively, with a mean follow-up of 23 months. Loss of patency was associated with both poor distal runoff (P = .007) and increasing number of stents used (P = .03). Early complications were seen in 4 patients including: stent oversizing leading to in-folding, perforation of a tibial artery, access site hematoma, and access vessel dissection. CONCLUSION: As experience with EVPAR continues to grow, caution must be applied in its use. Careful patient selection, proper operative technique, and correct vessel sizing are required for good outcomes. Poor distal runoff and use of numerous stents leads to diminished patency rates.

The benefit of early repair for a mycotic aortic aneurysm due to Yersinia enterocolitica infection.

Mycotic aortic aneurysms are infrequent but challenging cases. We present a 68-year-old man with evolving infrarenal aortic and right common iliac artery aneurysms from an infection with Yersinia enterocolitica. This is a rare but virulent cause of aortitis. The patient underwent open resection and debridement with anatomic reconstruction using an aortic homograft. He recovered well and quickly returned to normal functional status. This represents the first successful anatomic aortic repair using homograft with this organism. Here, we review the literature and outcomes associated with this unusual pathogen. With favorable anatomy and expedient operative management, good results can be obtained.

The utility of venous thromboembolism risk assessment models in general and vascular surgery.

Venous thromboembolism (VTE) is a common postsurgical complication, the incidence of which can be reduced with the use of various prophylactic measures. Proper use of these measures requires an understanding of each individual patient's risk of VTE. Risk assessment models have been developed to aid clinicians in quantifying the likelihood of an individual VTE formation. In this review, we discuss several models of risk assessment for general and vascular surgery patients with a focus on both sensitivity and prospective validation by external sources. In addition, strategies to improve proper implementation of prophylactic measures are highlighted.

A tale of two mothers.

This narrative describes the experience of the author's mother with pancreatic cancer from diagnosis to death. The author lives in the United States and his mother lived in India. Decisions about the type of care to seek, learning about palliative care, and the family's experience of seeking care at Pallium India are described. As a young Hindu boy in India, the author met Mother Theresa. He describes how her message of compassion to the young school boy became more clear and meaningful only after the loss of his mother when he appreciated the similar compassion shown by Mother Theresa and the staff of Pallium India.

Primary pancreatic neuroblastoma: an unusual tumor in infancy.

Fetal imaging has dramatically impacted neonatal care by providing an advanced warning of many different congenital anomalies. The advancements and widespread use of fetal imaging has, however, increased the identification of various incidental findings that is creating new challenges for neonatal diagnosis and treatment. We report such a case where a fetal pancreatic neuroblastoma (NB) was incidentally detected by computed tomographic scan of the maternal abdomen. Primary pancreatic NB is a very uncommon childhood neoplasm that, to our knowledge, has never been previously reported in the English language presenting in either the prenatal or neonatal periods. A 21-year-old woman complaining of acute abdominal pain and carrying a 35 weeks' gestation fetus was referred for computed tomographic scan because of the concern of maternal appendicitis. That scan was inconclusive for appendicitis but did incidentally detect a fetal mass in the general region of the pancreas. At 36 weeks' gestation, the fetus developed signs of distress, which prompted a cesarean delivery. Neonatal workup confirmed the presence of an abdominal mass in the region of the pancreas, but precise anatomic localization was not possible. Also noted on neonatal workup were elevated urinary catecholamines consistent with a hormonal active tumor. These findings prompted an abdominal exploration of this neonate, which revealed a solid tumor contained in the distal pancreas. The mass was managed by an uncomplicated distal pancreatectomy. The neonate fully recovered, and histologic diagnosis revealed NB, whereas the postoperative urine catecholamines normalized. This case underscores the unintended clinical challenges created by widespread fetal imaging, while presenting the first prenatally diagnosed case in the English language medical literature and earliest treated patient with pancreatic NB.

Solid pseudopapillary neoplasms of the pancreas: a multi-institutional study of 21 patients.

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPN) account for less than 1% of all pancreatic tumors. The goal of this study was to better understand the nature of these rare tumors through analysis of patients' clinical presentations and outcomes following surgical resection. METHODS: A multi-institutional retrospective review was conducted of all patients who underwent surgical resection from 1994 to 2008. RESULTS: Twenty-one patients were identified with SPN. Twenty patients were female. Median age at presentation was 34 y. The most common presenting symptom was abdominal pain (67%). All patients underwent resection: distal pancreatectomy (9), pancreaticoduodenectomy (5), central pancreatectomy (6), and laparoscopic excision/enucleation (1). A R(0) resection was obtained in all patients. Median tumor size was 5.5 cm. AJCC stages were stage I (18), stage II (1), stage III (2), and stage IV (0). Postsurgical complications occurred in 52% of patients, with pancreatic fistulae being the most common (29%). The median follow-up time was 55 mo. All patients remain alive without evidence of recurrence. CONCLUSION: Solid pseudopapillary neoplasms of the pancreas are atypical pancreatic tumors. SPN usually occur in young women who present with abdominal pain. Oncologic outcomes in patients who undergo surgical resection are excellent.

Proteomic approaches in neuroblastoma: a complementary clinical platform for the future.

Neuroblastoma (NB) is one of the most common solid tumors of childhood and displays a remarkable diversity in both biologic characteristics and clinical outcomes. Availability of high-throughput 'omics technologies and their subsequent application towards oncology has provided insight into the complex pathways of tumor formation and progression. Investigation of NB 'omics profiles may better define tumor behavior and provide targeted therapy with the goal of improving outcomes in patients with high-risk disease. Utilization of these technologies in NB has already led to advances in classification and risk stratification. The gradual emergence of NB-directed proteomics adds a layer of intricacy to the analysis of biologic organization but may ultimately provide a better comprehension of this complex disease. In this review, we cite specific examples of how NB-directed proteomics has provided information regarding novel biomarkers and possible therapeutic targets. We finish by examining the impact of high-throughput 'omics in the field of NB and speculate on how these emerging technologies may further be incorporated into the discipline.

Proteomic analysis of neuroblastoma microenvironment: effect of the host-tumor interaction on disease progression.

BACKGROUND: Children with advanced-stage neuroblastoma (NB) traditionally experience poor outcomes. Because early detection of advanced-stage disease may impact survival, finding new targets for early diagnosis is crucial. Evidence suggests the tumor microenvironment may have profound effects on cancer progression. METHODS: As little is known concerning the NB-host microenvironment, this study applied proteomic techniques, two-dimensional polyacrylamide gel electrophoresis (2D PAGE) combined with matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry to determine protein differences between cell cultured NB and tumors grown in mice for 2, 4, and 5 wk. RESULTS: We found an increase in proteins in cultured NB compared with implanted mouse tumors during tumor progression. Additionally, analyzing in vivo tumors to cultured NB, we observed less expressed proteins. However, 16 out of 19 proteins were of mouse origin, thus inferring host-derived factors contributing to tumor growth. CONCLUSION: We show that the dynamic relationship between NB and host microenvironment is important for tumor growth and better understanding of this milieu maybe relevant towards finding unique approaches for identifying advanced-stage disease.

Bin1 is linked to metastatic potential and chemosensitivity in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children. At the time of diagnosis, the tumor has metastasized in as many as 7 of 10 cases, and survival in high-risk patients remains poor. Accurate classification of high-risk patients is very important since this determines treatment plan, and although a consensus risk classification system has been established for NB, it contains few specific molecular markers that account for aggressive nature and metastatic potential of the tumor. Bin1 expression is reduced in breast, NB, and other cancer types and the reduction correlates with high-risk clinical features. Here we hypothesize that Bin1 has an inhibitory role in metastasis, and therefore decrease in its expression may be a marker of high-risk NB. PROCEDURE: Initially, breast cancer and NB cell lines derived from metastasis were examined for Bin1 expression. Then, a stable Bin1-overexpressing NB cell line was created and evaluated for in vitro metastatic behaviors using anoikis, invasion, and migration assays, and chemoresponsiveness using MTT assay. RESULTS: Reduced Bin1 was detected in all cancer cell lines examined, and forced Bin1 overexpression increased NB cell anoikis and enhanced the cell killing by doxorubicin. However, Bin1 overexpression did not significantly affect cell invasion, motility, or proliferation. CONCLUSIONS: Bin1 appears to function as a metastasis suppressor and chemosensitizer in NB, and resistance to anoikis may be an important metastatic mechanism. Thus, Bin1 expression status could serve as a marker for metastatic potential and chemosensitivity thereby allowing for more accurate classifications of high-risk NB patients.

Impact of omphalocele size on associated conditions.

PURPOSE: Omphalocele is often associated with the presence of other congenital anomalies. Case reports have demonstrated nonclassical associations occurring in smaller omphaloceles. The aim of this study was to determine if omphalocele defect size correlates with the type of anomalies found. METHODS: Patient records at a pediatric hospital were retrospectively reviewed for an 8-year period. Data were collected on patient demographics, omphalocele size, and congenital anomalies identified. Size of the abdominal wall defect was determined by either physical examination or operative record of repair. Patient cohorts were designated as those with small (4 cm and less) or large (greater than 4 cm) omphaloceles. RESULTS: Fifty-three cases of omphalocele were observed. Twenty-seven cases were classified as small, with 26 classified as large. A predominance of males was noted in the small omphalocele group (78% vs 42%; P = .01). Intestinal anomalies, including Meckel's diverticulum and intestinal atresia, were only seen in patients with small omphaloceles. Most cardiac anomalies were associated with large omphaloceles (34.6% vs 3.7%; P = .01). CONCLUSION: Small omphalocele size correlates with an increased prevalence of associated gastrointestinal anomalies, a lower prevalence of cardiac anomalies, and a higher predominance of male sex.

Applications of emerging molecular technologies in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Median survival from the time of diagnosis is less than a year, with less than 5% of patients surviving 5 years. These tumors are thought to arise through two different pathways. Primary GBMs represent de novo tumors, while secondary GBMs represent the malignant progression of lower-grade astrocytomas. Moreover, despite improvements in deciphering the complex biology of these tumors, the overall prognosis has not changed in the past three decades. The hope for improving the outlook for these glial-based malignancies is centered on the successful clinical application of current high-throughput technologies. For example, the complete sequencing of the human genome has brought both genomics and proteomics to the forefront of cancer research as a powerful approach to systematically identify large volumes of data that can be utilized to study the molecular and cellular basis of oncology. The organization of these data into a comprehensive view of tumor growth and progression translates into a unique opportunity to diagnose and treat cancer patients. In this review, we summarize current genomic and proteomic alterations associated with GBM and how these modalities may ultimately impact treatment and survival.

Three-dimensional neuroblastoma cell culture: proteomic analysis between monolayer and multicellular tumor spheroids.

INTRODUCTION: Solid tumors, such as neuroblastoma (NB), are associated with a heterogeneous cell environment. Multicellular tumor spheroid (MCTS) cultures have been shown to better mimic growth characteristics of in vivo solid tumors. Because tumor spheroid growth patterns may be quite different from standard two-dimensional culture systems, we sought to compare the protein expression profiles of two- and three-dimensional in vitro NB cultures, i.e., monolayers and MCTS. MATERIALS AND METHODS: Human NB cells were grown as both monolayers and spheres. Nuclear and cytosolic proteins were analyzed for differentially secreted proteins by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and selected polypeptides were identified by mass spectrometry (LC-MS/MS). RESULTS: Several metabolic (transketolase, triosephosphate isomerase, pyruvate kinase M1/M2, alpha enolase, and phosphoglycerate mutase-1), cell stress response (heat shock proteins (HSP) 90, 70, and 60; antioxidant, thioredoxin), cell structure (septin 2, adenyl cyclase-associated protein-1), tubulin beta-2 chain, actin, translationally controlled tumor protein and cofilin), signal transduction (peptidyl prolyl cis/trans isomerase A), biosynthetic (phosphoserine aminotransferase) and transport (cellular retinoic acid binding protein 1) polypeptides were overexpressed in spheroids. Several protein groups were differentially expressed between NB monolayers and spheroids. CONCLUSION: The altered proteins among NB spheroids may represent an important link between monolayer cell cultures and in vivo experiments and thus a more ideal in vitro culture system for determining the precise three-dimensional microenvironment of NB.