Severe Infectious Complications Research Articles

Prevention of severe infectious complications after colorectal surgery using preoperative orally administered antibiotic prophylaxis (PreCaution): study protocol for a randomized controlled trial

BackgroundColorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery.Methods/designThe PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out in The Netherlands. Adult patients who are scheduled for elective colorectal surgery are eligible to participate. In total, 966 patients will be randomized to receive the study medication. This will either be Pre-OP, a solution that consists of tobramycin and colistin sulphate, or a placebo solution. The study medication will be administered four times daily during the 3 days prior to surgery. Perioperative intravenously administered antibiotic prophylaxis will be administered to all patients in accordance with national infection control guidelines. The primary endpoint of the study is the cumulative incidence of deep SSIs and/or mortality within 30 days after surgery. Secondary endpoints include both infectious and non-infectious complications of colorectal surgery, and will be evaluated 30 days and/or 6 months after surgery.DiscussionTo date, conclusive evidence on the added value of preoperative orally administered antibiotic prophylaxis in colorectal surgery is lacking. The PreCaution trial should determine the effects of orally administered antibiotics in preventing infectious complications in elective colorectal surgery.Trial registrationNetherlands Trial Register, ID: NTR6113. Registered on 11 October 2016; EudraCT 2015-005736-17.

Effectiveness of the Initial Escalation of Immunochemotherapy in Patients with High Risk MALT-Lymphoma: Pilot Study Results

Background. MALT-lymphoma is usually characterized with an indolent course. The factors underlying the effectiveness of the standard chemotherapy in patients with MALT-lymphomas include MALT-IPI risk group and a high SUV<sub>max</sub> according to the results of positron emission tomography (PET). All well-known MALT-lymphoma risk factors indirectly indicate a high risk of transformation to large cell lymphoma. The search for an effective chemotherapy continues. Aim. To evaluate the effectiveness of the R-EPOCH/R-BAC escalated immunochemotherapy for MALT-lymphoma patients with poor prognosis factors. Materials & Methods. In the period of 2016-2017 the study included 5 female MALT-lymphoma patients (the mean age of 41 years), of which 1 patient had an early relapse after surgery and 4 patients were newly diagnosed. Prior to therapy 4 patients were evaluated with PET. The mean SUV<sub>max</sub> was 10.04. According to MALT-IPI 2 patients belonged to a high-risk group and 3 belonged to a middle-risk group. All the patients received R-EPOCH/R-BAC regimen therapy. A month after completing the treatment all the patients were again evaluated with PET. Results. In 4 patients with 10-24 months follow-up complete remission was reported, which was confirmed by the results of histology and PET. The treatment of 1 patient was not completed. The immunotherapy was well tolerated by the patients. Hematological toxicity grade 3-4 occurred only after completing R-BAC treatment regimens. No severe infectious complications were reported. Conclusion. MALT-lymphoma patients need to be evaluated in terms of all prognostic factors to identify the high-risk patients for whom escalated therapy is to be used already in the first line treatment. This pilot study of the use of R-EPOCH/R-BAC for treatment of MALT-lymphoma patients with poor prognosis factors yielded positive results and showed its acceptable tolerance.

Ibrutinib in the Treatment of Relapsed Chronic Lymphocytic Leukemia

Aim. To estimate ibrutinib efficacy in the treatment of early CLL relapses and in patients with > 2 lines of preceding therapy. Analysis of treatment results in patients with del(17p) and monitoring of minimal residual disease (MRD) and ibrutinib safety profile. Materials & Methods. The analysis included the results of ibrutinib treatment in 31 patients with CLL. Twenty eight patients were treated by bendamustine and fludarabine containing regimens. The median prior treatment lines were 2 (range 1-10). The indications for the treatment initiation were the first early relapse in 51 % of cases (n = 16) and a relapse after 2 and more lines of therapy in 49 % of cases (n = 15). Ibrutinib was administered in mono- (n = 15) and combined therapy (n = 14) as well as in the R-BAC scheme (n = 2). Using FISH analysis del(17p) was found in 9 patients (34 %). Results. Within the median follow up of 18 months (range 7-42+) the overall survival (OS) rate was reported to be 87 %, and the progression-free survival (PFS) rate was 77 %. The maximum MRD after a year of ibrutinib treatment was observed in case of combination with immunochemother-apy (e.g., R-BAC). Within the period of 18 months OS rate was 100 %, in the patient group with early relapses and 66 % in the group with a relapse after 2 and more therapy lines (p = 0.02). Within the same examination period PFS was significantly higher (94 %) in the patient group with early relapses compared to the previously treated patients (60 %) (p = 0.034). The most common adverse events were grade 1-2 purpura (30 %), grade 1-2 diarrhea (10 %), atrial fibrillation paroxysms (10 %) and arterial hypertension (10 %). Severe infectious complications registered in 6 % (n = 3) patients were successfully solved in the course of combined antibacterial and antimycotic treatment. Conclusion. Ibrutinib was shown to be effective drug for treatment of relapsed CLL. The OS and PFS values were more favourable in patients with early relapses compared to the patients with relapses after > 2 lines of therapy prior to ibrutinib treatment. The maximum elimination of the tumor clone was observed after combined ibrutinib/immunochemotherapy treatment. The tolerance of ibrutinib was reported to be satisfactory with acceptable toxicity profile. No mortality due to infection complications was observed.

Non-molecular Methods to Detect Bacteriuria Prior to Urological Interventions: A Diagnostic Accuracy Systematic Review

Urine culture still has to be considered as the gold standard to rule out bacteriuria and should, therefore, be obtained prior to invasive endoscopic or open urological procedures to minimize the risk of severe infectious complications.

Synthetic oleanane triterpenoids enhance blood brain barrier integrity and improve survival in experimental cerebral malaria

BackgroundCerebral malaria (CM) is a severe complication of Plasmodium falciparum infection associated with high mortality and neurocognitive impairment in survivors. New anti-malarials and host-based adjunctive therapy may improve clinical outcome in CM. Synthetic oleanane triterpenoid (SO) compounds have shown efficacy in the treatment of diseases where inflammation and oxidative stress contribute to pathogenesis.MethodsA derivative of the SO 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), CDDO-ethyl amide (CDDO-EA) was investigated for the treatment of severe malaria in a pre-clinical model. CDDO-EA was evaluated in vivo as a monotherapy as well as adjunctive therapy with parenteral artesunate in the Plasmodium berghei strain ANKA experimental cerebral malaria (ECM) model.ResultsCDDO-EA alone improved outcome in ECM and, given as adjunctive therapy in combination with artesunate, it significantly improved outcome over artesunate alone (p = 0.009). Improved survival was associated with reduced inflammation, enhanced endothelial stability and blood–brain barrier integrity. Survival was improved even when administered late in the disease course after the onset of neurological symptoms.ConclusionsThese results indicate that SO are a new class of immunomodulatory drugs and support further studies investigating this class of agents as potential adjunctive therapy for severe malaria.

Getting Your Head around Cerebral Malaria

Cerebral malaria is one of the most severe complications of human infection by the Plasmodium falciparum parasite. In this issue of Cell Host & Microbe, Kessler etal. (2017) provide valuable insights into the diagnosis and pathogenesis of this poorly understood manifestation of malaria.

HIV-associated pulmonary hypertension.

HIV-associated pulmonary arterial hypertension (HIV-PAH) is a well-recognized severe cardiovascular complication of HIV infection that confers an adverse prognosis irrespective of the stage of disease. This review will summarize the available data on HIV-PAH epidemiology and provide insights into the pathophysiology and therapeutic strategies currently available. Patients with HIV are several thousand times more likely to develop HIV-PAH compared to the incidence of idiopathic PAH. Several HIV viral proteins are implicated in the pathogenesis although the exact mechanism remains unknown. In the past two decades, there have been several new treatment strategies that appear effective in treating HIV-PAH. Novel pathophysiologic mechanisms implicating the transforming growth factor β receptor family may offer novel therapeutic targets in the future. As antiretroviral therapy continues to improve health outcomes for patients with HIV, there needs to be a shift in focus of care toward chronic noncommunicable diseases. Among cardiovascular disease-complicating chronic HIV infection, HIV-PAH is a severe progressive disease that leads to right heart failure and death. Currently available treatment strategies are effective, however, furthering our understanding of HIV-PAH will be critical as it is likely to become the commonest cause of PAH worldwide.

Evaluating the Risk of Viral Myocarditis following Influenza Infection among Hospitalized Patients during 2014–2015 and 2015–2016 Influenza Seasons

BackgroundMyocarditis is a severe cardiovascular complication of influenza infection that is often fatal and underdiagnosed. We evaluated the epidemiology of influenza myocarditis (IM) among inpatients at one institution.MethodsWe performed a retrospective cohort study of inpatients harboring influenza virus by reverse transcription-polymerase chain reaction from respiratory specimens between 2014 and 2016. We collected demographic, treatment, strain-typing, and hospitalization data for all patients. Definitive IM was proven by histopathology or viral isolation from myocardial tissue. Probable and possible IM were based on CDC and predefined clinical criteria, respectively. We used the chi-squared test to compare characteristics between 2014–2015 and 2015–2016 influenza seasons and the subset of patients with cardiovascular complications.ResultsWe identified 757 patients with influenza in 2014–2015 (n = 453) and 2015–2016 (n = 304). Baseline characteristics including gender, influenza type, and co-morbidities were similar between seasons except for more white and cardiovascular disease (P <0.005) in 2014–2015. Overall, five (0.7%) (2014–2015 = 4, 2015–2016 = 1) had probable IM. Median age was 65 years (range 29–87) and median length of stay was 4 days (range 4–15). All had EKG changes, one had increased heart size without effusion requiring ICU stay and intubation. Four received oseltamivir, and all survived.Possible IM occurred in 39 patients (5%) based on new EKG changes (58%), troponin elevation (38%) and pericardial effusion (2%). These patients were older (median 81 years, range 29–91) with longer length-of-stay (median 8 days, range 1–41). Oseltamivir was given to 30/39 (77%). Death occurred in 5/23 patients with EKG changes and 3/15 with troponin elevation.ConclusionIM was rare during the past two influenza seasons with no attributable mortality at our institution. Eight-fold more patients with IM were detected using a priori criteria when compared with CDC criteria with substantially higher mortality. This may represent a high-risk subset for whom future studies are needed to improve IM diagnosis and prevent morbidity and mortality.Disclosures All authors: No reported disclosures.

Fulminant Myopericarditis Complicated by Tamponade Due to Influenza A Infection in a Healthy Young Female

SESSION TITLE: Other Infections SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Viral myocarditis should be strongly considered in any previously healthy patient who presents with new symptoms of chest pain, shortness of breath and fevers. CASE PRESENTATION: A 37-year-old healthy female presented to outpatient clinic and was diagnosed with an upper respiratory infection. Three days later she presented to an emergency department after continued escalation of shortness of breath, fevers, and chest pain. She was found to be tachycardic and hypotensive. Laboratory evaluation revealed WBC 16.7 mcL with Troponin T 0.06 ng/dL and NT-Pro BNP 1209 pg/mL. CT angiography showed no evidence of pulmonary embolism but revealed a new pericardial effusion and bilateral pleural effusion. Echocardiography revealed a left ventricular ejection fraction (LVEF) of 57% and 1.1cm pericardial effusion. Influenza A PCR nasal swab returned positive and the patient was initiated on oseltamivir and intravenous steroids. Over the next 24 hours, the patient continued to deteriorate with worsening tachycardia and hypotension despite aggressive fluid resuscitation and vasopressor support. She was initiated on broad spectrum antibiotics despite negative bacterial respiratory and blood cultures throughout her hospitalization. Troponin T peaked at 0.77 ng/mL. Repeat echocardiography was concerning for tamponade physiology and ultimately an urgent pericardial window operation was performed. This failed to significantly stabilize the patient and she was transferred to a transplant capable center given concern for fulminant viral myocarditis. She underwent right ventricular biopsy under echo guidance, during which LVEF was noted as 42%. Biopsy returned without evidence of myocarditis. Supportive care was continued and gradually the patient’s tachycardia and hypotension improved. MRI was performed on hospital day 8 which showed patchy diffuse myocardial edema and sub-epicardial delayed enhancement with pericardial edema and effusion concerning for myopericarditis. DISCUSSION: Influenza myocarditis is a severe complication of influenza infection. The clinical course is variable, with cardiac sequela typically visible within seven days of infection. Complications are severe with approximately 37% of requiring advanced cardiac support therapy and mortality 25% in available case reports. CONCLUSIONS: During peak influenza season each winter patients presenting with symptoms of chest pain, shortness of breath and fevers should be evaluated for myocarditis given severe potential complications and mortality. Reference #1: Estabragh, Zahra Raisi, and Mamas A. Mamas. “The cardiovascular manifestations of influenza: a systematic review.” International journal of cardiology 167.6 (2013): 2397-2403. Reference #2: Sellers, Subhashini A., and William A. Fischer. “Myocarditis In Severe Influenza Infection: A Review Of The Literature.” D40. CRITICAL CARE: DIAGNOSING AND TREATING BACTERIAL AND VIRAL INFECTIONS IN THE ICU. American Thoracic Society, 2016. A6906-A6906. DISCLOSURE: The following authors have nothing to disclose: Conor Senecal, Thomas Tilbury No Product/Research Disclosure Information

The Role of Cytomegalovirus in Congenital and Early Postnatal Infections in Northeastern Bulgaria.

Human cytomegalovirus is a ubiquitous, large enveloped DNA β-herpesvirus that, like other herpesviruses, establishes lifelong latency following primary infection. It is the most frequent cause of congenital, neonatal and early postnatal infections with long lasting sequelae. The aim of the present study was to assess the prevalence of cytomegalovirus among a cohort of newborns and 1-3-month-old children with neurological symptoms, physical retardation, prolonged jaundice, thrombocytopenic purpura and other disabilities. The study was a retrospective cross-sectional analysis of serological screening data for detection of specific anti-cytomegalovirus IgM and IgG in children from Northeastern Bulgaria. Between 2003 and 2015, average prevalences of 18.8% (95% CI: 15.4 to 22.2) for anti-CMV IgM antibodies (suggesting acute infection) and 84.7% (95% CI: 81.6 to 87.8) for anti-CMV IgG antibodies were measured in a total number of 517 samples. The prevalence rate of anti-CMV IgM in 1-3-month-old children was 4-fold higher than that in newborns [25.8% (95% CI: 21.1 to 30.5) and 6.4% (95% CI: 2.9 to 9.9, respectively]. In contrast, no significant difference was found for anti- CMV IgG positivity between newborns and 1-3-month-old infants (84% and 85%, respectively). The data obtained strongly encourage screening of pregnant women for anti-CMV IgG and IgM to avoid transmission of the infection and severe complications of congenital infection.

"Pancreas-Compressionless Gastrectomy": A Novel Laparoscopic Approach for Suprapancreatic Lymph Node Dissection.

In radical operations for gastric cancer, a balance between the quality of lymph node dissection and safety of surgery must be ensured. During suprapancreatic lymphadenectomy in laparoscopic gastrectomy (LG), an adequate operative field should be safely and effectively established to reduce pancreas-related complications. We present a novel approach that avoids direct compression of the pancreas in LG and describe the surgical outcomes of this method. We historically compressed the pancreas during suprapancreatic lymph node dissection in LG to obtain an adequate operative field but have since modified our operative technique. In our new method introduced in March 2016, the operative field is established by pulling and controlling the connective tissues along the inferior border of the pancreas and the nerves along the common hepatic and splenic arteries, instead of directly compressing the pancreas itself. We compared 51 patients in the compression group (January 2015-February 2016) and 45 patients in the compressionless group (March 2016-January 2017) in terms of surgical outcomes, including the amylase concentration in the drainage fluid and postoperative complications. The amylase concentrations in the compressionless group were significantly lower on postoperative days 1 and 3 (p<0.001 and p=0.013, respectively) compared with the compression group. The rates of severe postoperative pancreatic fistula and intra-abdominal infectious complications decreased from 11.8 to 2.2% (p=0.116) and from 17.6 and 2.2% (p=0.018), respectively. Our approach, termed "pancreas-compressionless gastrectomy," can be considered a safe and useful method to prevent postoperative infectious complications in LG.

Autologous thyroid cartilage graft implantation in medialization laryngoplasty: a modified approach for treating unilateral vocal fold paralysis

Medialization laryngoplasty is the standard surgical treatment for unilateral vocal fold paralysis. This study presents a modified approach in which a thyroid cartilage graft is implanted in medialization laryngoplasty. 22 patients who underwent this approach were included in the study. The results revealed that glottal incompetence and vocal performance were markedly improved following surgery, and the follow-up period ranged from 6 to 74 months (mean, 21.4 months). Acoustic analysis revealed significant improvements in the maximum phonation time (from 3.51 to 7.89 seconds, p < 0.001), F0 (from 221.7 to 171.0 Hertz, p = 0.025), and jitter (from 7.68 to 3.19, p < 0.001). Perceptual assessment revealed a significant decrease in voice grading (from 2.59 to 1.41, p < 0.001), roughness (from 1.82 to 1.23, p = 0.004), and voice breathiness (from 2.55 to 1.23, p < 0.001). None of the patients exhibited severe wound infection, tissue rejection, or other complications attributed to the surgical procedure. In conclusion, autologous thyroid cartilage implantation in medialization laryngoplasty medializes the vocal cord, minimizes the glottal gap, and improves the voice of patients with vocal fold paralysis. This procedure is characterized by simplicity, safety, and acceptable results.

Ten thousand kilometre transfer of cardiogenic shock patients on venoarterial extracorporeal membrane oxygenation for emergency heart transplantation: Cooperation between Reunion Island and Metropolitan France.

There is no heart transplantation centre on the French overseas territory of Reunion Island (distance of 10,000 km). The aim of this study was to describe the characteristics of cardiogenic shock adult patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) who were transferred from Reunion Island to mainland France for emergency heart transplantation. This retrospective observational study was conducted between 2005 and 2015. The characteristics and outcome of cardiogenic shock patients on VA-ECMO were compared with those of cardiogenic shock patients not on VA-ECMO. Thirty-three cardiogenic shock adult patients were transferred from Reunion Island to Paris for emergency heart transplantation. Among them, 19 (57.6%) needed mechanical circulatory support in the form of VA-ECMO. Median age was 51 (33-57) years and 46% of the patients had ischaemic heart disease. Patients on VA-ECMO presented higher Sequential Organ Failure Assessment score ( p = 0.03). No death occurred during the medical transfer by long flight, while severe complications occurred in 10 patients (30.3%). Incidence of thromboembolic events, severe infectious complications and major haemorrhages was higher in the group of patients on VA-ECMO than in the group of patients not on VA-ECMO ( p <0.01). Seven patients from the VA-ECMO group (36.8%) and six patients from the non-VA-ECMO group (42.9%, p=0.7) underwent heart transplantation after a median delay of 10 (4-29) days on the emergency waiting list. After heart transplantation, one-year survival rates were 85.7% for patients on VA-ECMO and 83.3% for patients not on VA-ECMO ( p=0.91). This study suggests the feasibility of very long-distance medical evacuation of cardiogenic shock patients on VA-ECMO for emergency heart transplantation, with acceptable long-term results.

Proteomic profiling of the brain of mice with experimental cerebral malaria

Cerebral malaria (CM) is a severe neurological complication of malaria infection in both adults and children. In pursuit of effective treatment of CM, clinical studies, postmortem analysis and animal models have been employed to understand the pathology and identify effective interventions. In this study, a shotgun proteomics analysis was conducted to profile the proteomic signature of the brain tissue of mice with experimental cerebral malaria (ECM) in order to further understand the underlying pathology. To identify CM-associated response, proteomic signatures of the brains of C57/Bl6N mice infected with P. berghei ANKA that developed neurological syndrome were compared to those of mice infected with P. berghei NK65 that developed equally high parasite burdens without neurological signs, and to those of non-infected mice. The results show that the CM-associated response in mice that developed neurological signs comprise mainly acute-phase reaction and coagulation cascade activation, and indicate the leakage of plasma proteins into the brain parenchyma. SignificanceCerebral malaria (CM) remains a major cause of death in children. The majority of these deaths occur in sub-Saharan Africa. Even with adequate access to treatment, mortality remains high and neurological sequelae can be found in up to 20% of survivors. No adjuvant treatment to date has been shown to reduce mortality and the pathophysiology of CM is largely unknown. Experimental cerebral malaria (ECM) is a well-established model that may contribute to identify and test druggable targets. In this study we have identified the disruption of the blood-brain barrier following inflammatory and vascular injury as a mechanism of disease. In this study we report a number of proteins that could be validated as potential biomarkers of ECM. Further studies, will be required to validate the clinical relevance of these biomarkers in human CM.

Allelic variants of immune response genes in children with infectious complications during the treatment of acute leukemia

Infectious complications that arise during the treatment of children with acute leukemia with chemotherapeutic agents at high doses represent a serious problem in oncohematology. To find genetic conditions that may lead to the development of postchemotherapy infections, the genomes of 12 children with acute leukemia who had severe infectious complications during therapy were examined. At the same time, the coding regions of 17 genes involved in the regulation of the immune response were determined by massive parallel sequencing. The analysis revealed 39 nonsynonymous SNPs that lead to amino acid substitutions, including the following informative genetic markers: PTPN22 c.1858C>T (rs2476601), TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791), IL7R c.197T>C (rs1494555) and IL7R c.412G>A (rs1494558). The results of massive parallel sequencing were validated by Sanger sequencing. The identification of genetic markers associated with the predisposition to infectious complications may allow one to assess the individual risk of the severe infection development in children with acute leukemia during the treatment with chemotherapeutic agents and to begin the development of personalized approaches to anticancer therapy.

Efficacy and safety of TNF antagonists in ocular sarcoidosis: data from the French registry STAT.

Backgroung: This study investigated the efficacy and safety of TNF antagonists in sarcoid uveitis in unselected cases. Design: This is a multicentre study on patients with sarcoidosis who received TNF antagonists in pneumology and internal medicine departments in France. We present here the subgroup of patients with biopsy-proven sarcoid uveitis included in the nationwide registry STAT (Sarcoidosis treated with TNF AnTagonists). Results: Among the 132 patients included in this multicenter study, 18 patients with refractory uveitis were treated as a first-line TNF antagonist with infliximab (n=14), adalimumab (n=3) and certolizumab (n=1). Before anti-TNF initiation, the median duration of sarcoidosis was 42 months and 83% of the patients have been treated with at least one immunosuppressive drug. Six patients switched for a second-line TNF antagonist. After a mean time under treatment of 29 months, the treatment resulted in a significant decrease of the ophthalmic extrapulmonary Physician Organ Severity Tool (ePOST) (mean score: 4.2 vs. 2.6) scores and a steroid sparing effect (29.4±20.7 vs. 6.2±5.2 mg/d). Overall, the ophthalmic response, either complete or partial, was 67%. Nine patients (50%) presented adverse events, including severe infectious complications in 5 patients, which required anti-TNF treatment interruption in 6 cases (33%). Among the 7 responder patients who discontinued anti-TNF therapy, 71% relapsed. Finally, 12 patients (67%) could continue TNF antagonist treatment. Conclusions: TNF antagonists were efficient in 67% of biopsy-proven refractory sarcoid uveitis. Severe adverse events, mainly infectious complications, were frequent. The high frequency of relapses after anti-TNF-α discontinuation requires a close patient follow-up thereafter. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 74-80).

Bortezomib combined with standard induction chemotherapy in Japanese children with refractory acute lymphoblastic leukemia.

Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study. Four-dose bortezomib (1.3mg/m2/dose) combined with two standard induction chemotherapies was used. Prolonged pancytopenia (grade 4) was observed in all patients. Four of the six patients developed severe infectious complications. Peripheral neuropathy (grade 2) occurred in five patients. The individual plasma bortezomib concentration-time profiles were not related to toxicity and efficacy. Five patients were evaluable for response, and four patients achieved complete response (CR) or CR without platelet recovery (80%). In conclusion, four-dose bortezomib (1.3mg/m2/dose) combined with standard re-induction chemotherapy was associated with a high risk of infectious complications induced by prolonged neutropenia, although high efficacy has been achieved for Japanese pediatric patients with refractory ALL. Attention must be given to severe infectious complications when performing re-induction chemotherapy including bortezomib.

Study of Malaria Parasite with Special Reference to Liver Function Test of the Patient Attending at TMU Hospital Moradabad (U.P)

Background: Malaria is an important infectious vector borne disease caused by a Plasmodium species. Liver involvement in severe Plasmodium falciparum infection is commonly a significant cause of morbidity and mortality among humans. Objective: In this study, we show the correlation of malaria positive cases with liver derangement. Methods: The present study had been conducted in Teerthankar Mahaveer Medical college Hospital and Research Center, Moradabad, U.P. from February 2014 to January 2015 on both IPD & OPD patients .Results: The present study included 200 clinically suspected cases of Malaria with derange Liver function. 67.5% patients show increased level of Total and indirect bilirubin followed by 45% of patient shows increased level of direct bilirubin. 27.5% patient’s shows increased level SGPT followed by 40% of SGOT. Conclusions: Deranged liver functions are commonly seen as a complication of severe malarial infection.

A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali. Two SNPs of IL22, rs1012356 (P = 0.016, OR = 2.12) and rs2227476 (P = 0.007, OR = 2.08) were independently associated with CM in a sample of 115 Nigerian children with CM and 160 controls. The association with rs2227476 (P = 0.01) was replicated in 240 nuclear families with one affected child from Mali. SNP rs2227473, in linkage disequilibrium with rs2227476, was also associated with CM in the combined cohort for these two populations, (P = 0.004, OR = 1.55). SNP rs2227473 is located within a putative binding site for the aryl hydrocarbon receptor, a master regulator of IL-22 production. Individuals carrying the aggravating T allele of rs2227473 produced significantly more IL-22 than those without this allele. Overall, these findings suggest that IL-22 is involved in the pathogenesis of CM.

A novel kindred with inherited STAT2 deficiency and severe viral illness

A novel kindred with inherited STAT2 deficiency and severe viral illness