Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring

Background/Aims@#Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD). @*Methods@#Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. @*Results@#One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively. @*Conclusions@#Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Interferon-gamma release assay has poor diagnostic accuracy in differentiating intestinal tuberculosis from Crohn’s disease in tuberculosis endemic areas

Background/Aims@#Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. @*Methods@#Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL.Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. @*Results@#Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. @*Conclusions@#In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.

Treatment of Post - traumatic Bone Defects with infection in L ong B ones

Background: Open fractures are a challenging condition to treat because they are frequently compounded by infection and nonunion. Traditional bone defect care strategies are mostly focused on fracture union rather than infection prevention. The goal of this study is t o use the Masquelet approach to examine the outcome of a post - traumatic defect with infection in long bones. This method is a two - step process. Stage I surgery includes debridement and the placement of an antibacterial spacer in the bone defect. Stage II s urgery involved removing the spacer while preserving the induced membrane that had grown on the spacer's surface and filling the bone - gap with morselized iliac crest bone - graft within the membrane sleeve. Methods: There were 22 patients in this study (18 m ales and 4 females), all of them had infected long bone fractures with a bone defect. The average length of the bone defect was 3.5 centimetres. The duration of follow - up varied from 6 to 15 months. Results: After an average of 11.5 weeks following the fir st step of surgery, radiological union was achieved. After stage 1, no patient had any remaining infection. After radiological union, all of the patients were able to mobilise with full weight bearing and a satisfactory range of motion in the adjoining joi nts. Conclusion: With favourable outcomes, this treatment can be used on infected fractures with bone loss on a regular basis. Antibiotic cement spacers, used in conjunction with complete debridement, minimise the risk of infection. The graft is revascular ized through induced biomembrane. In most circumstances, union may be predicted; nonetheless, the length of time it takes to reach an agreement is a constraint. The technique is low - cost and does not necessitate any additional training or equipment. Despit e the fact that it is a two - stage procedure, it does not necessitate several surgeries as in traditional approaches.

Clinical presentation of COVID-19 in patients with inflammatory bowel disease: a systematic review and meta-analysis

Background/Aims@#Coronavirus disease 2019 (COVID-19) is recognized to have variable clinical manifestations. The clinical presentation of patients with inflammatory bowel disease (IBD) having COVID-19 is unclear. @*Methods@#We identified articles reporting about the clinical presentation of COVID-19 in those with underlying IBD from PubMed and Embase. The studies, irrespective of design or language, were included. The overall pooled frequency of various symptoms was estimated. Joanna Briggs Institute Critical appraisal checklist was used to assess the quality of studies. @*Results@#Eleven studies, including 1,325 patients, were included in the pooled analysis. The pooled estimates for clinical presentation were; fever: 67.53% (95% confidence interval [CI], 45.38–83.88), cough: 59.58% (95% CI, 45.01–72.63), diarrhea: 27.26% (95% CI, 19.51–36.69), running nose: 27% (95% CI, 15.26–43.19) and dyspnea: 25.29% (95% CI, 18.52–33.52). The pooled prevalence rates for abdominal pain, nausea and vomiting were 13.08% (95% CI, 9.24–18.19), 10.08% (95% CI, 5.84–16.85) and 8.80% (95% CI, 4.43–16.70) per 100 population, respectively. @*Conclusions@#The clinical presentation of COVID-19 in IBD patients is similar to the general population.

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018-2021)

Cancer, which is the uncontrolled growth of cells, is the second leading cause of death after heart disease. Targeting drugs, especially to specific genes and proteins involved in growth and survival of cancer cells, is the prime need of research world-wide. Indole moiety, which is a combination of aromatic-heterocyclic compounds, is a constructive scaffold for the development of novel leads. Owing to its bioavailability, high unique chemical properties and significant pharmacological behaviours, indole is considered as the most inquisitive scaffold for anticancer drug research. This is illustrated by the fact that the U.S. Food and Drug Administration (FDA) has recently approved several indole-based anticancer agents such as panobinostat, alectinib, sunitinib, osimertinib, anlotinib and nintedanib for clinical use. Furthermore, hundreds of studies on the synthesis and activity of the indole ring have been published in the last three years. Taking into account the facts stated above, we have presented the most recent advances in medicinal chemistry of indole derivatives, encompassing hot articles published between 2018 and 2021 in anticancer drug research. The recent advances made towards the synthesis of promising indole-based anticancer compounds that may act via various targets such as topoisomerase, tubulin, apoptosis, aromatase, kinases, etc., have been discussed. This review also summarizes some of the recent efficient green chemical synthesis for indole rings using various catalysts for the period during 2018-2021. The review also covers the synthesis, structure‒activity relationship, and mechanism by which these leads have demonstrated improved and promising anticancer activity. Indole molecules under clinical and preclinical stages are classified into groups based on their cancer targets and presented in tabular form, along with their mechanism of action. The goal of this review article is to point the way for medicinal chemists to design and develop effective indole-based anticancer agents.

Disparities in All-cancer and Lung Cancer Survival by Social, Behavioral, and Health Status Characteristics in the United States: A Longitudinal Follow-up of the 1997-2015 National Health Interview Survey-National Death Index Record Linkage Study

Most research on cancer patient survival uses registry-based (e.g., SEER) incidence and survival data that have limited socioeconomic status and health-risk information. In this study, we used the 1997-2015 National Health Interview Survey-National Death Index prospectively-linked pooled cohort database (n = 40,291 cancer patients) to examine disparities in patient survival by a broad range of social determinants, including race/ethnicity, nativity, educational attainment, income/poverty level, occupation, housing tenure, physical and mental health status, smoking, physical activity, body mass index, and alcohol consumption. We used Cox proportional hazards models to estimate mortality hazard ratios and cause-specific 1-year, 5-year, and 10-year survival rates for all-cancer and lung cancer. During 1997-2015, the 10-year age-adjusted (all-cause) survival rate for cancer patients with professional and managerial occupations was 89.66%, significantly higher than the survival rate of 83.17% for laborers or 83.66% for the unemployed. Cancer patients with renting house had significantly lower age-adjusted survival rates than those owning house (82.65% vs. 85.80%). The 10-year age-adjusted survival rates were significantly greater among cancer patients with regular physical activity than those without regular physical activity (90.18% vs. 83.24%). Age-adjusted survival rates were significantly reduced for cancer patients with lower income and education, poor health, and serious psychological distress, and among current and former smokers. The gap in survival narrowed with additional sociodemographic, health, or behavioral adjustment. Similarly large differentials were found in lung cancer survival. Marked disparities in all-cancer and lung cancer survival were found by a wide range of sociodemographic and health characteristics.

Seroprevalence of antibodies to SARS-CoV-2 and predictors of seropositivity among employees of a teaching hospital in New Delhi, India

Objectives@#Healthcare workers (HCWs) are at a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to the increased likelihood of clinical exposure during patient management. The study objective was to determine the seroprevalence of antibodies to SARS-CoV-2 and its predictors among hospital employees. @*Methods@#The cross-sectional study was conducted at a teaching hospital from August 2020 to September 2020 among 1,401 employees, including 1,217 HCWs, in New Delhi, India. The serum samples were examined for immunoglobulin G (IgG) antibodies to SARS-CoV-2 using the COVID Kavach-Anti-SARS-CoV-2 IgG Antibody Detection enzyme-linked immunosorbent assay kit. Data were collected electronically using the EpiCollect mobile platform. A p<0.05 was considered to indicate statistical significance. @*Results@#A total of 169 participants (12.1%) had detectable IgG antibodies to SARS-CoV-2. The highest seropositivity rate was observed in the administrative staff (20.1%), while it was lowest among medical doctors (5.5%, p<0.001). Male sex and ever having lived in a containment zone were independently associated with past infection with SARS-CoV-2. @*Conclusion@#The seroprevalence of SARS-CoV-2 infection in health workers may be lower than in the general population in New Delhi. However, nonpharmaceutical interventions were not associated with a reduction in the risk of acquisition of SARS-CoV-2.

Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing

Background@#The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. @*Methods@#We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. @*Results@#There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2–257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1–31/case), while PB showed variations in 51 genes (1–29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). @*Conclusions@#The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.

Seroprevalence of antibodies to SARS-CoV-2 and predictors of seropositivity among employees of a teaching hospital in New Delhi, India

Objectives@#Healthcare workers (HCWs) are at a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to the increased likelihood of clinical exposure during patient management. The study objective was to determine the seroprevalence of antibodies to SARS-CoV-2 and its predictors among hospital employees. @*Methods@#The cross-sectional study was conducted at a teaching hospital from August 2020 to September 2020 among 1,401 employees, including 1,217 HCWs, in New Delhi, India. The serum samples were examined for immunoglobulin G (IgG) antibodies to SARS-CoV-2 using the COVID Kavach-Anti-SARS-CoV-2 IgG Antibody Detection enzyme-linked immunosorbent assay kit. Data were collected electronically using the EpiCollect mobile platform. A p<0.05 was considered to indicate statistical significance. @*Results@#A total of 169 participants (12.1%) had detectable IgG antibodies to SARS-CoV-2. The highest seropositivity rate was observed in the administrative staff (20.1%), while it was lowest among medical doctors (5.5%, p<0.001). Male sex and ever having lived in a containment zone were independently associated with past infection with SARS-CoV-2. @*Conclusion@#The seroprevalence of SARS-CoV-2 infection in health workers may be lower than in the general population in New Delhi. However, nonpharmaceutical interventions were not associated with a reduction in the risk of acquisition of SARS-CoV-2.

Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing

Background@#The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. @*Methods@#We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. @*Results@#There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2–257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1–31/case), while PB showed variations in 51 genes (1–29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). @*Conclusions@#The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.

Computed-Tomography staging of Breast Cancer and its role in Patient Management in a resource-limited setting: A retrospective study from Fiji

@#Breast cancer is now the leading cause of mortality from cancer in Women in Fiji. State of the art diagnostic measures such as MRI, PET scanning and advanced tumour markers are unavailable in many LMIC countries including Fiji, but CT is becoming more widely available. The aim of the study was to determine the association between CT/anatomical staging and prognosis in a resource-limited setting, and its role in planning appropriate treatment strategies. This was a retrospective, analytical study of the data from the Colonial War Memorial Hospital Oncology department tumour register recorded between 2013 and 2018. The mean age of the breast cancer patients with confirmed diagnosis was 54.93 years with SD of 12.4 years. There was a 40% 3 year mortality rate. CT reports were available for 196 patients. Poor prognosis was very closely associated with Tumour size (p=0.002, OR 0.26 (0.10-0.63)), Nodes (p<0.001, OR 0.25 (0.13-0.48.)) and Metastases (p<0.001, OR 0.13 (0.07- 0.25)).The lungs were the most frequent site of metastases. CT staging enables accurate TNM classification, which is closely associated with prognosis. In the absence of advanced cytopathological and imaging modalities CT staging has an important part to play in planning appropriate treatment.

Co-existence of AML1-ETO and BCR-ABL1 transcripts in a relapsed patient of acute myeloid leukemia with favorable risk group: a coincidence or clonal evolution?

Prognosis of acute myeloid leukemia relies heavily on the cytogenetic and molecular abnormalities. AML1-ETO fusion protein resulting from t[8;21], a recurring cytogenetic abnormality, is known to be associated with favorable prognosis. Additional molecular defects may, however, co-operate with the fusion proteins and alter the course of the disease. Among the additional cytogenetic defects, presence of Philadelphia [Ph] chromosome has rarely been documented in this subtype. Little is known about the consequences of its interactions with AML1-ETO, and its effect on morphological and clinical picture. Moreover, Ph[+] clones or subclones may appear at any point during the disease course. We herein report one such unusual case of a 26-year-old female, who was diagnosed to have t[8;21] and managed accordingly. During disease relapse after 2.5 years, the bone marrow showed extensive eosinophilia and basophilia. Subsequent molecular testing showed the presence of BCR-ABL in addition to the AML1-ETO fusion product

Development of a High-Resolution Multi-Locus Microsatellite Typing Method for Colletotrichum gloeosporioides

Colletotrichum gloeosporioides is an economically important fungal pathogen causing substantial yield losses indifferent host plants. To understand the genetic diversity and molecular epidemiology of this fungus, we have developed a novel, high-resolution multi-locus microsatellite typing (MLMT) method. Bioinformatic analysis of C. gloeosporioides unannotated genome sequence yielded eight potential microsatellite loci, of which five, CG1 (GT)(n), CG2 (GT1)(n), CG3 (TC)(n), CG4 (CT)(n), and CG5 (CT1)(n) were selected for further study based on their universal amplification potential, reproducibility, and repeat number polymorphism. The selected microsatellites were used to analyze 31 strains of C. gloeosporioides isolated from 20 different host plants from India. All microsatellite loci were found to be polymorphic, and the approximate fragment sizes of microsatellite loci CG1, CG2, CG3, CG4, and CG5 were in ranges of 213–241, 197–227, 231–265, 209–275, and 132–188, respectively. Among the 31 isolates, 55 different genotypes were identified. The Simpson's index of diversity (D) values for the individual locus ranged from 0.79 to 0.92, with the D value of all combined five microsatellite loci being 0.99. Microsatellite data analysis revealed that isolates from Ocimum sanctum, Capsicum annuum (chili pepper), and Mangifera indica (mango) formed distinct clusters, therefore exhibited some level of correlation between certain genotypes and host. The developed MLMT method would be a powerful tool for studying the genetic diversity and any possible genotype-host correlation in C. gloeosporioides.

Urinary tract infection in children after cardiac surgery: Incidence, causes, risk factors and outcomes in a single-center study

Nosocomial urinary tract infection [UTI] increases hospitalization, cost and morbidity. In this cohort study, we aimed to determine the incidence, risk factors, etiology and outcomes of UTIs in post-operative cardiac children. To this end, we studied all post-operative patients admitted to the Pediatric Cardiac Intensive Care Unit [PCICU] in 2012, and we divided the patients into two groups: the UTI [UTI group] and the non-UTI [control group]. We compared both groups for multiple peri-operative risk factors. We included 413 children in this study. Of these, 29 [7%] had UTIs after cardiac surgery [UTI group], and 384 [93%] were free from UTIs [control group]. All UTI cases were catheter-associated UTIs [CAUTIs]. A total of 1578 urinary catheter days were assessed in this study, with a CAUTI density rate of 18 per 1000 catheter days. Multivariate logistic regression analysis demonstrated the following risk factors for CAUTI development: duration of urinary catheter placement [p < 0.001], presence of congenital abnormalities of kidney and urinary tract [CAKUT] [p < 0.0041] and the presence of certain syndromes [Down, William, and Noonan] [p < 0.02]. Gram-negative bacteria accounted for 63% of the CAUTI. The main causes of CAUTI were Klebsiella [27%], Candida [24%] and Escherichia coli [21%]. Resistant organisms caused 34% of CAUTI. Two patients [7%] died in the UTI group compared with the one patient [0.3%] who died in the control group [p < 0.05]. Based on these findings, we concluded that an increased duration of the urinary catheter, the presence of CAKUT, and the presence of syndromes comprised the main risk factors for CAUTI. Gram-negative organisms were the main causes for CAUTI, and one-third of them found to be resistant in this single-center study

Performance and carcass characteristics of guinea fowl fed on dietary Neem [Azadirachta indica] leaf powder as a growth promoter

The present work aimed at studying growth pattern and carcass traits in pearl grey guinea fowl fed on dietary Neem [Azadirachta indica] leaf powder [NLP] over a period of 12 weeks. Day old guinea fowl keets [n=120] were randomly assigned to four treatment groups, each with 3 replicates. The first treatment was designated as control [T[0]] in which no supplement was added to the feed, while in treatments T[1], T[2] and T[3], NLP was provided as 1, 2 and 3 g per kg of feed, respectively. The results revealed a significant increase in body weight at 12 weeks; 1229.7 for T[1], 1249.8 for T[2], and 1266.2 g T[3] compared to 1220.0 g for the control group [P<0.05]. The results also showed that the supplementation of NLP significantly increased feed intake [P

Predictors of renal replacement therapy and mortality in children with chronic kidney disease

To study the epidemiology of chronic kidney disease [CKD] in children, and to look for risk factors to predict renal replacement therapy [RRT] and mortality. This is a retrospective cohort study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 2006 and 2014, where the files of 1,000 children with CKD were reviewed. We determined the effect of consanguinity and hypertension, and being a Saudi indigene on mortality and RRT. We compared children with congenital versus non-congenital causes of CKD. The mean +/- standard deviation age at presentation was 4.9 +/- 4.3 years. The median duration of follow up was 1.5 [interquartile range [IQR]: 0.4-4.0] years. Only 9.7% of children received RRT, and 8.3% died. The underlying etiology for CKD was congenital in 537 children. The congenital CKD group presented at a younger age group [3.5 +/- 4.0 versus 6.6 +/- 3.9 years, p<0.0001], had more advanced stages of CKD [p<0.0001], higher rates of consanguinity [75.4% versus 47.1%, p<0.0001], and RRT [p<0.004] than children with non-congenital CKD. Risk factors for RRT among children with CKD include being a Saudi indigene [relative risk [RR]=1.49, 95% confidence interval [CI]: 1.01-2.21], and hypertensive [RR=5.29, 95% CI: 3.54-7.91]. The risk factor for mortality was hypertension [RR=2.46, 95% CI: 1.66-3.65]. Congenital causes of CKD represent the main etiology of CKD in children living in the western province of Saudi Arabia. Significant risk factors for RRT include congenital CKD, Saudi nationality, and hypertension. Hypertension is also a predictor of mortality in children with CKD

single institution 18-years retrospective analysis of malignant melanoma

Melanoma accounts for about 2% of all cancer-related mortality in western populations. Surgical excision of localized disease is curative in many patients with 80% overall 5-year survival rate. There are many indicators of prognosis of which tumor burden is predicted by primary site with nodal status being the next most important variable. Patients with advanced stage have very high risk of developing distant metastases and should receive systemic therapy. Despite treatment, majority of locally advanced patients develop metastatic disease. A retrospective analysis of cases of malignant melanoma registered over a period of eighteen years, from October 1990 to September 2007 was done. Patient profile, presentation, disease load, treatment protocols and response on or after treatment were analyzed. The median age at diagnosis in men was 48 years and 50 years in women. At presentation, more than half of studied cases [56.5%] presented with nodal metastases at diagnosis while about three fourths [74%] had distant metastases [stage IV disease]. More than half [56%] of the patients had superficial spreading type. The most common presenting complaints were swelling [70% of patients], ulcer [50% of patients] or pain [50%]. Primary sites included extremities, central nervous system, abdomen, trunk, and bones. Liver, brain, abdomen and lungs were common metastatic sites. Surgical excision of primary lesion was done in about half of the cases. Four patients subsequently received palliative radiotherapy and two more received adjuvant radiotherapy. Another six patients received adjuvant chemotherapy and radiotherapy. Among treated patients, 26% showed partial response and another 8% have stable disease while 65% patients progressed on or after initial treatment. Malignant melanoma carries an overall poor prognosis especially in advanced stages. Multimodality therapy with surgery, radiotherapy and chemotherapy may provide local or nodal remission but cannot improve long term survival in advanced cases

Glycopeptide and daptomycin susceptibility trends among clinical isolates of methicillin-resistant Staphylococcus aureus in a tertiary care center in North India

Increased vancomycin minimum inhibitory concentration [MIC] levels in Staphylococcus aureus and their association with vancomycin treatment failure are well-known problems. Few studies have recognized progressive increases in glycopeptide MIC levels for S. aureus strains in recent years. This study determined glycopeptide and daptomycin susceptibility among methicillin resistant S. aureus [MRSA] strains. A total of 776 clinical isolates of MRSA recovered from 2009 to 2012 were studied for glycopeptide and daptomycin susceptibility using the E-test method. The vancomycin MIC geometric mean [GM] of the MRSA isolates was 0.923, 0.944, 1.134 and 1.294 mg/L in the years 2009, 2010, 2011 and 2012, respectively, and the trend significantly increased over the years [P< 0.0001]. Similarly, the teicoplanin MIC GM was 1.47, 1.49, 1.8 and 2.04 mg/L in the years from 2009 to 2012, respectively [P< 0.0001]. MIC shifts were not found for daptomycin [P> 0.232]. A significant increase in the MIC for glycopeptides was observed among the clinicalA. MRSA isolates at our center over a 4-year period. However, the daptomycin MIC did not increase in the observed MRSA isolates

safety of ultrasound guided central venous cannulation in patients with liver disease

Central venous cannulation [CVC] is frequently required during the management of patients with liver disease with deranged conventional coagulation parameters [CCP]. Since CVC is known to be associated with vascular complications, it is standard practice to transfuse Fresh-Frozen Plasma or platelets to correct CCP. These CCP may not reflect true coagulopathy in liver disease. Additionally CVC when performed under ultrasound guidance [USG-CVC] in itself reduces the incidence of complications. To assess the safety of USG-CVC and to evaluate the incidence of complications among liver disease patients with coagulopathy. An audit of all USG-CVCs was performed among adult patients with liver disease in a tertiary care center. Data was collected for all the adult patients [18-60 years] of either gender suffering from liver disease who had required USG-CVC. Univariate and multivariate regression analysis was done to identify possible risk factors for complications. The mean age of the patients was 42.1 +/- 11.6 years. Mean international normalized ratio was 2.17 +/- 1.16 whereas median platelet count was 149.5 [range, 12-683] × 10[9] /L. No major vascular or non-vascular complications were recorded in our patients. Overall incidence of minor vascular complications was 18.6%, of which 13% had significant ooze, 10.3% had hematoma formation and 4.7% had both hematoma and ooze. Arterial puncture and multiple attempts were independent risk factors for superficial hematoma formation whereas low platelet count and presence of ascites were independent risk factors for significant oozing. Ultrasound guidance -CVC in liver disease patients with deranged coagulation is a safe and highly successful modality

comparative evaluation of the effect of intravenous dexmedetomidine and clonidine on intraocular pressure after suxamethonium and intubation

In patients with penetrating eye injury and a full stomach, suxamethonium is still used for rapid sequence induction of anesthesia. But its use is associated with the rise in intraocular pressure [IOP] and this can result in permanent vision loss in these patients. Dexmedetomidine and clonidine are two alpha-2 adrenergic agonist drugs which prevent the rise in IOP. The aim of this study is to compare the efficacy of intravenous [i.v.] dexmedetomidine and clonidine in preventing an increase in IOP after administration of suxamethonium and tracheal intubation. Sixty patients undergoing elective nonophthalmic surgery under general anesthesia were included in this clinical study. Patients were randomly assigned into three groups to receive 0.5 mcg/kg dexmedetomidine [Group D], 2 mcg/kg clonidine [Group C] or normal saline [Group S] as premedication i.v. over a period of 10 min before induction. IOP, heart rate, and mean arterial pressure were recorded before and after premedication, after suxamethonium, after intubation and then after 5 min. Following administration of dexmedetomidine and clonidine IOP decreased in both groups. After suxamethonium IOP increased in all three groups but it never crossed the baseline in Group D and C. After laryngoscopy and intubation IOP again increased in all three groups but in dexmedetomidine group it never crossed the baseline whereas in clonidine group it was significantly higher than the baseline. Single i.v. dose of dexmedetomidine premedication [0.5 mcg/kg] blunt the IOP and hemodynamic response to suxamethonium injection and tracheal intubation more effectively than single i.v. dose of clonidine premedication [2 mcg/kg]