Effect of Smoking on Seminal Plasma Vitamin B6 in Fertile and Subfertile Men.

Despite extensive documentation of the negative consequences of smoking on a wide range of diseases and disorders, the direct effect of smoking on seminal plasma vitamin B6 (vitB6) concentration is not addressed yet. Here, we attempted to examine the influence of smoking on the levels of seminal plasma vitB6 in fertile and subfertile males. One hundred and ninety-five participants were categorized into two groups: fertile men (smokers (n = 32), nonsmokers (n = 43)) and subfertile men (smokers (n = 65), nonsmokers (n = 55)). According to the World Health Organization criteria, conventional semen analysis was performed for all subjects involved in the study. The concentration of vitB6 in semen samples was measured by high-performance liquid chromatography tandem-mass spectrometry. There was no significant difference in the mean seminal plasma concentrations of vitB6 in smokers versus nonsmokers in both fertile (p=0.5096) and subfertile (p=0.5224) groups. Besides, no significant correlations were observed between seminal plasma concentration of vitB6, duration of smoking, and men's age in all tested groups. In conclusion, these findings elucidate that smoking has no significant impact on the levels of seminal plasma vitB6 in both fertile and subfertile men.

A rare incidence of severe dermatological toxicities triggered by concomitant administration of all-trans retinoic acid and triazole antifungal in patients with acute promyelocytic leukemia: a case series and review of the literature.

BACKGROUND: All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous xerosis, rash, and pruritus are well reported, ATRA associated severe dermatological toxicities are extremely rare. ATRA is primary metabolized by cytochrome P450 (CYP450) enzyme system, and triazole antifungals are notorious for their strong inhibitory effect on CYP450. CASE PRESENTATION: Three Asian APL patients experienced rare ATRA-induced severe dermatological toxicities: exfoliative dermatitis (ED) in cases 1 and 2, and necrotic scrotal ulceration in case 3. Both case 1 (33-year-old female), and case 2 (28-year-old male) landed in emergency department with dehydration, generalized skin erythema and xerosis during their induction chemotherapy. Both of these patients also developed invasive aspergillosis and required concomitant triazole antifungals during their chemotherapy. For ED, intravenous fluids and broad-spectrum antibiotics were started along with application of local emollients to prevent transdermal water loss. Although their general condition improved but skin exfoliation continued with complete desquamation of palms and soles. Dermatology was consulted, and clinical diagnosis of ED was established. Discontinuation of ATRA resulted in complete resolution of ED. Case 3 (15-year-old boy) reported two blackish mildly tender scrotal lesions during induction chemotherapy. He also had mucocutaneous candidiasis at presentation and was kept on triazole antifungal. Local bacterial & fungal cultures, and serological testing for herpes simplex virus were reported negative. Despite adequate local care and optimal antibiotic support, his lesions persisted, and improved only after temporary discontinuation of ATRA. After a thorough literature review and considering the temporal association of cutaneous toxicities with triazole antifungals, we speculate that the concomitant use of triazole antifungals inhibited the hepatic metabolism of ATRA, resulting in higher serum ATRA concentration, and markedly accentuated cutaneous toxicities in our patients. CONCLUSION: By highlighting this crucial pharmacokinetic interaction, we want to caution the fellow oncologists to be mindful of the inhibitory effect of triazole antifungals on CYP450. We propose using a non-myelosuppressive combination of ATRA and arsenic trioxide for management of APL hence, obliterating the need of prophylactic antifungals. However, in the event of invasive fungal infection (IFI), we suggest using alternative class of antifungals.

Situational analysis of antimicrobial stewardship program (ASP) among public and private sector tertiary care hospitals in Karachi, Pakistan: A qualitative case study.

Objective: To assess the current status of implementation of the Antimicrobial Stewardship Program (ASP) across Tertiary Care Hospitals in Karachi, Pakistan. Design: Exploratory qualitative case study. Setting: Public and private tertiary care hospitals in Karachi, Pakistan. Participants and Methods: The study data were collected from 3 public and 4 private tertiary care hospitals. Twenty-eight in-depth interviews were conducted from the Chief Executive Officer, Chief Medical Officer, Medical Superintendent, and departmental heads of internal medicine, general surgery, and pediatric, respectively. Purposive sampling was done to include higher and middle managers, whereas the infectious diseases consultant, infectious diseases/clinical pharmacist, and clinical microbiologist were interviewed through snowball sampling methodology. Analysis was done using NVivo. Data were source-triangulated within and among the study setting and study participants. Results: We found that more than two-thirds (n = 5, 71%) of tertiary care hospitals in Karachi do not have a structured ASP which includes major public sector hospitals (n = 3, 43%) and half of the private sector hospitals (n = 4, 29%). The study results led to four broad themes, (1) ASP structure, (2) ASP interventions, (3) hospital medical record-keeping system, and (4) structured way for analyzing and reporting mechanism of data related to the ASP. At H1 and H2, there was a consistency in ASP structure and interventions, whereas paucity seen among remaining tertiary care hospitals. Conclusion: There is an alarming need for ASP in the public and private sector hospitals in Karachi. This study can inform future stakeholders regarding ASP and strategies for structural change at hospitals.

New trends in immunocastration and its potential to improve animal welfare: a mini review.

Castration is frequently used to reduce aggressive behavior and improve the meat quality of animals. Traditionally, surgical and mechanical castration are used to sterilize the animals, but these approaches are associated with a high level of pain, stress, long recovery periods, and post-operative infections. Immunocastration is a new animal-friendly, painless alternative castration technique that is used to prevent undesired sexual behavior, reduce aggressive behavior, prevent unwanted pregnancy, control wildlife populations and wandering species, enhance growth performance, improve meat quality, and treat various sex hormone-dependent disorders. The mechanism of immunocastration includes the immunological block of the hypothalamic-pituitary-gonadal axis (HPG axis) which inhibits gonadotropin secretions, causes atrophy of gonadal tissues, and inhibits gametogenesis, resulting in infertility in both female and male mammals. By the mid-1990s, various immunocastration vaccines have been tested in different animal models to achieve successful castration effects. Recently, genetic immunocastration especially DNA vaccine has gained increasing attention due to its safety, being animal-friendly, and being easy to use. This review aims to evaluate the potential of traditional castration methods, as well as the current status of immunocastration vaccines, their effects, and future prospective.

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan.

OBJECTIVES: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. METHODS: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. RESULTS: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. CONCLUSIONS: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

Successful management of colistin- and carbapenem-resistant Klebsiella pneumoniae-associated ecthyma gangrenosum in acute myeloid leukemia: A rare complication.

Pseudomonal ecthyma gangrenosum is a well-known condition in immunosuppressed patients. However, ecthyma gangrenosum associated with Klebsiella pneumoniae is a rare entity that requires early recognition and optimal antibiotic and surgical management. We herein report the first case of colistin & carbapenem-resistant Klebsiella pneumoniae ecthyma gangrenosum in an acute myeloid leukemia patient. A 30-year-old female with acute myeloid leukemia received induction chemotherapy at the National Institute of Blood Diseases and Bone Marrow Transplantation hospital. Post-chemotherapy, she developed fever and a necrotic erythematous papule on right forearm. Colistin-susceptible carbapenem-resistant Klebsiella pneumoniae was isolated in cultures. Susceptibility testing was performed by microbroth dilution method. Worsening necrotic lesion prompted surgical debridement. Histopathology of debrided tissue revealed necrotic inflammation, and tissue cultures grew colistin-resistant carbapenem-resistant Klebsiella pneumoniae (colistin minimum inhibitory concentration >4 µg/mL). We speculate that colistin resistance was acquired due to impaired antibiotic penetration in necrotic nidus. A higher incidence of carbapenem-resistant Klebsiella pneumoniae-associated ecthyma gangrenosum is anticipated in hem-oncology patients, and timely diagnosis, appropriate antibiotics, and surgical debridement remain the only potential cure.

Possible Beneficial Effects of Fresh Pomegranate Juice in SARS-CoV-2 Infection Conditions.

Rather than the prophylactic vaccination, any effective synthetic, natural, or nutritional therapy or regimen that may cure or remedy, albeit partially, the complications of SARS-CoV-2 should be highly acknowledged. Here, we reviewed and discussed possible beneficial biological effects of pomegranate juice in such diseased condition of viral infection based on the current published evidence (direct and indirect) and owing to the robust evidence that fresh pomegranate juice is highly rich with unique bioactive compounds that are approved in various occasions to be effective in several chronic diseased conditions. All related references that serve our aim are accessed through available electronic databases, particularly PubMed and Scopus. In summary, there is accepted evidence that pomegranate juice may be beneficial in SARS-CoV-2 infection conditions, especially for patients with the clinical history of chronic diseases such as hypertension, cardiovascular disease, diabetes, and cancer. However, the interventional studies that directly probe and confirm the effectiveness of fresh pomegranate juice in the management of SARS-CoV-2 infection are mandatory.

Potentially Preventable Mortality in the Pediatric Intensive Care Unit: Findings from a Retrospective Mortality Analysis.

Objective The goal of this study was to estimate the proportion and causes of potentially preventable mortality among critically ill children admitted to the pediatric intensive care unit (PICU). Methods The medical records of all patients who died in the PICU (age range: one month to 16 years) between January 2014 and December 2015 were evaluated by two independent reviewers to determine whether there had been any delayed recognition of deteriorating conditions, delayed interventions, unintentional/unanticipated harm, medication errors, adverse reactions to transfusions, and hospital-acquired infections that could have resulted in unanticipated death. Preventability was labeled on a 6-point scale. Results During the study period, 92 of 690 patients did not survive [median age: 60 months, interquartile range (IQR): 114]. The median Pediatric Risk of Mortality (PRISM) III score was 17 (IQR: 6). Major diagnostic categories included sepsis (n = 29, 35%), central nervous system diseases (n = 16, 17%), oncological/hematological diseases (n = 6, 6%), cardiac diseases (n = 4, 4%), and miscellaneous conditions. None of the deaths had definitive or strong evidence of preventability. Four (4.3%) patients were in category 4 (i.e., possibly preventable, >50/50 chance), 15 (16.3%) in category 3 (possibly preventable, <50/50 chance), 28 (30.4%) had some evidence of preventability, and 45 (49.0%) were labeled as definitely not preventable. Late identification (diagnostic error) of the worsening condition in four (21.0%) patients, slow intervention in six (31.6.0%), and hospital-acquired infections in 10 (52.6%) were found to be related to potentially preventable mortality. Conclusions Preventable diagnostic errors and nosocomial infections (NIs) are major contributors to preventable mortality. Structured mortality analysis provides actionable information for future preventive strategies. Improvement in care processes, including clinical decision support systems, could help reduce preventable mortality rates.

Surgical-site infections in emergency abdominal paediatric surgeries at a tertiary-care hospital in Pakistan.

A retrospective chart review was carried out in children (neonates to 18 years) who underwent acute surgical abdominal exploration during 2012-2016 at the Aga Khan University Hospital, Karachi, to evaluate the postoperative surgical site infection rates in emergency paediatric abdominal surgery. Incidence of surgical site infection (SSI) was estimated. P-value was calculated, chisquare and non-parametric tests were performed by comparing pre-surgical and post-surgical procedure pathogen occurrence and pre-procedure wound status. Pathogen occurrence related to time-trend of 98 paediatric patients who underwent emergency abdominal surgery was plotted. Of the 94 who were discharged in stable condition, it was found that there was no significant difference between pre- and postsurgical pathogens. Escherichia coli (n=10) was found to be the most common pathogen. Contaminated wounds were associated with higher SSI (p=0.036, OR 1.95 95% CI 0.7-5.4). The study found that pre-surgery wound status could be an indicator for risk of SSI in a post-operative scenario.

Testosterone in Males as Enhanced by Onion (Allium Cepa L.).

Testosterone (17ß-Hydroxyandrost-4-en-3-one) is the main sex hormone in males. Maintaining and enhancing testosterone level in men is an incessant target for many researchers. Examples of such research approaches is to utilize specific types of food or dietary supplements as a safe and easily reached means. Here, specifically, since 1967 until now, many research studies have revealed the effect of onion on testosterone; however, this link has yet to be collectively reviewed or summarized. To accomplish this contribution, we searched the Scopus, Web of Science, and PubMed databases for full articles or abstracts (published in English language) from April 1967 through December 2018 using the keywords "onion" versus "testosterone". In addition, a number of related published articles from the same databases were included to improve the integrity of the discussion, and hence the edge of the future directions. In summary, there is an evidence that onions enhance testosterone level in males. The mechanisms by which this occurs is mainly by increasing the production of luteinizing hormone, enhancing the antioxidant defense mechanism in the tests, neutralizing the damaging effects of the generated free radicals, ameliorating insulin resistance, promoting nitric oxide production, and altering the activity of adenosine 5'-monophosphate -activated protein kinase. However, this effect requires further approval in humans, mainly by conducting clinical trials.

Fertility testing for men before marriage: Is it acceptable?

Addressing male infertility issue before marriage, at least to the mate and her family, seems reasonable to avoid several psychosocial, economic and biological consequences. Here, we intended to comprehend whether fertility testing (i.e. semen analysis) for men before marriage is acceptable and can be applied in Jordanian society. To achieve this contribution, we designed a questionnaire that shows the opinion of a sample of the Jordanian population in applying fertility testing for men before marriage. A total of 740 adult individuals (>18 years old, 364 males, 382 females) were selected randomly from different martial, economic, social, ethnic, religious and education statuses to fill the questionnaire. A total of 523 (70.11%) participants had a positive attitude towards applying fertility testing for men before marriage. This opinion was found not to be affected by gender (p = 0.305), age (p = 0.329), body mass index (p = 0.061), smoking (p = 0.059), monthly income (p = 0.094), education level (p = 0.131) and family members with infertility (p = 0.074); while, it is found to be affected by the social status of the participant (p = 0.004). In conclusion, applying fertility testing for men before marriage appears to be acceptable in Jordanian society.

Role of Uric Acid in Semen.

Since 1963, various research studies and reports have demonstrated the role of uric acid (2,6,8-trihydroxypurine), an end product of adenosine and guanosine catabolism, on semen quality and sperm function. However, this effect has not yet been collectively discussed, even though uric acid has been a well-recognized constituent in semen. Here, we systematically and comprehensively discuss and summarize the role/effect of uric acid in semen quality by searching the main databases for English language articles considering this topic. Additionally, certain significant and relevant papers were considered to support discussions and perceptions. In conclusion, uric acid contributes to maintaining and enhancing sperm motility, viability, and morphology; therefore, protecting sperm function and fertilizing ability. This contribution is performed mainly by neutralizing the damaging effect of oxidizing (e.g., endogenous free radicals and exogenous toxins) and nitrating agents and enhancing certain bioactive enzymes in spermatozoa. In contrast, high levels of uric acid may induce adverse effects to sperm function, at least in part, by reducing the activity of vital enzymes in spermatozoa. However, further research, mainly clinical, is still required to fully explore the role/effect of uric acid in semen.

Effect of metformin on semen quality

ABSTRACT Various studies have linked metformin, a universally antidiabetic drug, with semen quality; however, such a direct link has not been established. This review systematically addresses and summarizes the effect of metformin on semen quality, particularly sperm function. We searched the MEDLINE electronic database for English articles and abstracts containing the key words 'metformin' and 'sperm', and relevant articles were reviewed. In summary, metformin appears to have improved and provided positive impact on sperm quality. This effect may be due to the ability of metformin to reduce oxidative stress and lipid peroxidation, enhance 5'-AMP activated protein kinase activity, and restore the normal levels of pituitary-gonadal hormones. However, further clinical research is still necessary to confirm such effect.

Use of N-acetylcysteine in children with fulminant hepatic failure caused by acute viral hepatitis.

OBJECTIVE: To determine the efficacy of N-acetylcysteine (NAC) in children aged > 1 month to 16 years admitted with Fulminant Hepatic Failure (FHF) secondary to Acute Viral Hepatitis (AVH) in a tertiary care center of a developing country. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Department of Paediatrics, The Aga Khan University Hospital, Karachi, Pakistan, from January 2007 to December 2011. METHODOLOGY: Medical records of children (> 1 month - 16 years) with FHF admitted with AVH of known etiology who received NAC were reviewed retrospectively. Liver function tests (mean ± SD) at baseline, 24 hours after NAC and before or at the time of discharge/death were recorded and compared via using repeated measures ANOVA(r-ANOVA). Efficacy of NAC is defined in improvement in biochemical markers, liver function test and discharge disposition (survived or died). Mortality associated risk factors were identified by using logistic regression analysis. P-value and 95% confidence interval were recorded. RESULTS: Forty children (mean age was 80 ± 40 months) with FHF secondary to AVH received NAC. Majority were males (n=25; 63%). Vomiting (75%) and jaundice (65%) were the main presenting symptoms, one-third had hypoglycemic, while 40% had altered sensorium at the time of admission. There was significant statistical difference in liver enzymes and prothrombin time on admission comparing at discharge in children received NAC (p < 0.001). Fifteen (38%) children died. Severe vomiting {Odds Ratio (OR) 0.22, 95% Confidence Interval (CI) 0.05 - 0.8}, jaundice (OR 9.3, CI 1.1 - 82.6), inotropic support (OR 20.6, CI 3.5 - 118.3) and mechanical ventilation (OR 4.3, CI 1.1 - 16.6) at the time of admission are associated with risk factors for mortality in children with FHF secondary to AVH. CONCLUSION: NAC used in children with FHF secondary to AVH is associated with markedly improved liver function tests and recovery. FHF with complications is high risk for mortality.

Empyema thoracis in children: clinical presentation, management and complications.

OBJECTIVE: To determine the etiology, clinical manifestation, management (medical and surgical) and complications of children with empyema thoracis in a tertiary care hospital from Karachi, Pakistan. STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Department of Surgery, The Aga Khan University Hospital, Karachi, from January 1996 to December 2010. METHODOLOGY: Medical records of admitted children aged > a month to 15 years with discharge diagnosis of empyema thoracis and data was collected on demographic features, clinical manifestation, management and complications. Children managed medically were compared with those managed surgically by using interquartile range and median comparison. Mann-Whitney U test was used to compare age in months, weight (kg) and length of stay in days and presenting complaint, duration of illness; chi-square test was used to compare thrombocytosis in between groups and p-value was calculated. RESULTS: Among the 112 patients, 59 (53%) were younger than 5 years of age. Males (n=83, 74%) were predominant. Fifty (45%) children were admitted in winter. Thirty (27%) children found unvaccinated and one fourth (n=27; 24%) were severely malnourished. Fever, cough, and dyspnea were the major presenting symptoms. Sixty-six (59%) were on some antibiotics prior to admission. Staphylococcus aureus (n=13) and Streptococcus pneumoniae (n=5) were the commonest organism isolated from blood and pleural fluid cultures. Majority of the children required some surgical intervention (n=86). Surgically managed children were younger (p=0.01); had less weight (p=0.01) and prolonged fever (p=0.02); and stayed longer in hospital (p < 0.001) as compared to medically managed children. Requiring readmission (n=8), subcutaneous emphysema (n=5) and recollection of pus (n=5) were the major complications. CONCLUSION: Staphylococcus aureus was the major organism associated with paediatric empyema thoracis. Early identification and empiric antibiotic as per local data is essential to prevent short and long-term complications. Younger, lower weight children with prolonged fever required surgical management.

Posterior mediastinal branchial cleft cyst: an unusual site.

A two and a half year old Kenyan girl presented with recurrent chest infections and difficulty in swallowing. Her clinical and laboratory workup was suggestive of lower respiratory tract infection for which she received a course of antibiotics; however, she remains symptomatic after the management of her suspected diagnosis. Therefore, further radiological workup including a chest CT scan and barium study were performed. This showed a homogeneous mass surrounded by ascending and descending aorta in the posterior mediastinum that was compressing the middle esophagus. She had a posterolateral thoracotomy which revealed a cystic mass with smooth surfaces (5x5 cm) in the posterior mediastinum. Histopathology showed branchial cleft cyst predominately lined by stratified squamous epithelium, with lymphocytes predominance. A final diagnosis of posterior mediastinal branchial cleft cyst was made. She was discharged home and remained well at follow-up.

Impact of maternal education about complementary feeding on their infants' nutritional outcomes in low- and middle-income households: a community-based randomized interventional study in Karachi, Pakistan.

This cluster-randomized interventional trial at periurban settings of Karachi was conducted to evaluate the impact of maternal educational messages regarding appropriate complementary feeding (CF) on the nutritional status of their infants after 30 weeks of educational interventions delivered by trained community health workers. Mothers in the intervention group received three education modules about breastfeeding (BF) and appropriate CF at a baseline visit and two subsequent visits 10 weeks apart. The control group received advice about BF according to national guidelines. Infants' growth [weight, length, and mid-upper arm-circumference (MUAC), stunting, wasting, and underweight] were measured at four time points. At the end of the study, infants in the intervention group had a higher mean weight of 350 g (p=0.001); length of 0.66 cm (p=0.001), and MUAC of 0.46 cm (p=0.002) compared to the controls; proportionate reduction of stunting and underweight were 10% (84% vs. 74%; OR(adj) 8.36 (5.6-12.42) and 5% (25% vs. 20%; OR(adj) 0.75 (0.4-1.79) in the intervention compared to the control group. For relatively food-secure populations, educational interventions about appropriate CF to mothers had a direct positive impact on linear growth of their infants.

Anthracycline-induced cardiotoxicity: prospective cohort study from Pakistan.

OBJECTIVES: To identify anthracycline-induced acute (within 1 month) and early-onset chronic progressive (within 1 year) cardiotoxicity in children younger than 16 years of age with childhood malignancies at a tertiary care centre of Pakistan. DESIGN: Prospective cohort study. SETTING: Aga Khan University, Karachi, Pakistan. PARTICIPANTS: 110 children (aged 1 month-16 years). INTERVENTION: Anthracycline (doxorubicin and/or daunorubicin). OUTCOME MEASUREMENTS: All children who received anthracycline as chemotherapy and three echocardiographic evaluations (baseline, 1 month and 1 year) between July 2010 and June 2012 were prospectively analysed for cardiac dysfunction. Statistical analysis including systolic and diastolic functions at baseline, 1 month and 1 year was carried out by repeated measures analysis of variance. RESULTS: Mean age was 74±44 months and 75 (68.2%) were males. Acute lymphoblastic leukaemia was seen in 70 (64%) patients. Doxorubicin alone was used in 59 (54%) and combination therapy was used in 35 (32%). A cumulative dose of anthracycline <300 mg/m(2) was used in 95 (86%). Fifteen (14%) children developed cardiac dysfunction within a month and 28 (25%) children within a year. Of these 10/15 (66.6%) and 12/28 (43%) had isolated diastolic dysfunction, respectively, while 5/15 (33.3%) and 16/28 (57%) had combined systolic and diastolic dysfunction. Seven (6.4%) patients expired due to severe cardiac dysfunction. Eight of 59 (13.5%) children showed dose-related cardiotoxicity (p=<0.001). Cardiotoxicity was also high when the combination of doxorubicin and daunorubicin was used (p=0.004). CONCLUSIONS: Incidence of anthracycline-induced cardiotoxicity is high. Long-term follow-up is essential to diagnose its late manifestations.

Acute lymphoblastic leukemia in a child with Fanconi's anaemia.

Fanconi anaemia (FA) is an autosomal recessive inherited disorder with progressive bone marrow failure, associated congenital malformation and solid and haematological malignancies. Acute myeloid leukemia is the commonest haematological malignancy followed by myelodysplastic syndrome in children with FA. FA transformed into acute lymphoblastic leukemia (ALL) is a rare phenomenon and one of the rarest haematological malignancies associated with this disorder. We are reporting a 13 years old girl with FA and positive chromosomal breakage. She required regular blood product transfusion. She was planned for haematopoietic stem cell transplantation (HSCT) but the sibling-matched donor was found to have chromosomal breaks as well. Later on, her peripheral smear showed blast cell. Bone marrow showed pre-B ALL. She was started on chemotherapy but died shortly due to complications of the treatment. For this rare condition conservative management is indeed essential, however, safe and appropriate chemotherapy regimen is needed.

Vasculogenic mimicry: a new prognostic sign of gastric adenocarcinoma.

Vasculogenic mimicry (VM) has been generally recognized as a new pattern of tumor neovascularization. It presents in many human malignancies. Till now, there is no report about VM in gastric adenocarcinoma (GAC). In this study, we collected 173 paraffin-embedded human GAC samples, with detailed follow-up and clinicopathologic data. CD31/ periodic acid-Schiff (PAS) double staining, immunohistochemical staining of CK8 & 18 and laminin were performed to validate the existence of VM in GAC. Microvascular density (MVD) and vasulogenic mimicry density (VMD) were counted respectively. VM was observed in 40 of the 173 GAC patients, especially in poorly differentiated GAC (P = 0.014). Patients with VM were prone to hematogenous metastasis and distant recurrence compared with patients without VM (P = 0.020, 0.029). Higher VMD values was also associated with hematogenous metastasis (P = 0.003). Immunohistochemical staining index (SI) of hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 were compared between the VM and non-VM group. The SI of four factors were all higher in the VM group than those of non-VM group (P = 0.000, 0.000, 0.004, 0.009, respectively). The Kaplan-Meier survival analysis showed that the VM group has shorter life span compared with non-VM group (P = 0.022). Cox proportional hazards model indicated that the presence of VM and TNM stage were independent predictors of poor prognosis (P = 0.039 and 0.004) for GAC. In conclusion, VM exists in GAC, especially in poorly differentiated GAC. Additionally, it is an unfavorable prognostic indictor for GAC. Hypoxia may play a role in VM formation in GAC.