Laparoscopic drainage of cryptogenic liver abscess

Background

To retrospectively compare the outcomes of percutaneously drained and laparoscopically drained liver abscesses.

Methods

Eight-five consecutive patients with radiological evidence of liver abscess were treated at National University Hospital of Singapore from 2005 to 2011. Multivariable logistic regression was used to identify failures of intervention. This was defined as persistent objective signs of sepsis. Complications, length of antibiotic therapy, and hospital stay were recorded but not used as indicators for failure of intervention. A propensity score analysis was used to adjust for possible confounders.

Results

Twenty-seven (40.3 %) patients in the percutaneous group did not respond to primary intervention compared to 2 patients (11.1 %) in the laparoscopic group (p = 0.020). Two patients within the percutaneous group died from progression of sepsis despite intervention. In the multivariate model with propensity score, laparoscopic drainage had a protective effect against failure compared to percutaneous drainage of liver abscess (odds ratio [OR], 0.03; 95 % confidence interval [CI], [0–0.4]; p = 0.008). There were no differences in complications related to the intervention (p = 0.108). Mean duration of antibiotics (p = 0.437) and hospital stay (p = 0.175) between the groups was similar.

Conclusions

Laparoscopic drainage of cryptogenic liver abscesses should be considered as an option for drainage of liver abscess.     

Circulating microparticle tissue factor,thromboembolism and survival in pancreaticobiliary cancers

Background

Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.

Patients and Methods

Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.

Results

The study population comprised 117 patients, including pancreatic (n = 80), biliary (n = 34) or unknown primary histologically consistent with PBC (n = 3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n = 15), deep venous thrombosis (n = 21) and other arterial or venous events (n = 32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity < 2.5 pg/mL (p < 0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).

Conclusions

Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.     

Clinico – diagnostic and therapeutic relevance of computed tomography scan of brain in children with partial seizures

Background:

Therapeutic relevance of computed tomography (CT) in children with partial seizures is reported to be remarkably low (1-2%). However, in the developing countries where infections involving the nervous system are common, routine CT scan of brain may help in finding treatable causes of seizures.

Objective:

Aim of this study was to evaluate the significance of CT scan of brain in the management of children with partial seizures.

Materials and Methods:

Children with partial epilepsy, whose predominant seizure type was focal motor seizures, were included in the study. CT scan of brain was done in all children aged between 1 month and 12 years with partial seizures of unknown etiology prospectively. The clinical findings of these children were noted along with the CT findings.

Results:

Between August 2001 and July 2002, of the 200 children with seizure disorder 50 children who satisfied the inclusion criteria were included in the study. CT scan of brain was normal in 16 children (32%) and was abnormal in 34 children (68%). Twenty children (~60% of abnormal scan) had potentially correctable lesions: Tuberculoma (n = 13), neurocysticercosis (n = 3), and brain abscess (n = 4). Five children had changes representing static pathology that did not influence patient management. The clinical features correlated with CT findings in 78% children.

Conclusion:

Children with partial motor seizures have high probability of having abnormal findings on CT scan of brain, especially, neuro-infections which are potentially treatable. Therefore, CT scan brain should be carried out in all children with partial motor seizures especially, in developing countries.     

Transitional services for adolescents with epilepsy in the UK: A survey

PurposeTo survey the current transitional epilepsy services in tertiary paediatric neurology centres in the UK within the principles of transitional care for young people with epilepsy.MethodsAn online web-based questionnaire was sent to the lead epilepsy clinicians in tertiary paediatric neurology centres on behalf of the British Paediatric Epilepsy Group, the specialist epilepsy group of the British Paediatric Neurology Association (BPNA). A transition clinic was defined as a ‘clinic or service that provided joint paediatric and adult supervision of care from paediatric to adult services’.ResultsTwenty-three centres were approached of which18 responded and 15 of which provided auditable data. The clinics were held between three and 12 times per year, mostly in the afternoon and sited equally between the paediatric and adult centre. Approximately three to five new, and three to eight follow up patients were seen in each clinic. Most clinics accepted new referrals with a minimum age of 14 and a maximum of 20 years. Most young people were seen only once in a transition clinic before then being promoted into the adult epilepsy service. Very few clinics accepted direct referrals from the GP. Adult, slightly more than the paediatric team provided out-of-hospital advice after the young person was seen in the transition clinic.ConclusionsYoung people with epilepsy are a challenging, but interesting group and their care at this time may have a potentially irreversible impact on their life. Their progress from paediatric to adult services should be a dynamic, gradual and smoothly transitioned process to optimise their care. Although recommended by the National Institute for Health and Clinical Excellence (NICE) and the National Services Framework (NSF), the findings of this survey would suggest an un-met need of this population.     

A novel semi-mechanistic tumor growth fraction model for translation of preclinical efficacy of anti-glypican 3 antibody drug conjugate to human

The growing fraction (GF) of tumor has been reported as one of the predictive markers of the efficacy of chemotherapeutics. Therefore, a semi-mechanistic model has been developed that describes tumor growth on the basis of cell cycle, allowing the incorporation of the GF of a tumor in pharmacokinetic/pharmacodynamic (PK/PD) modeling. Efficacy data of anti-glypican 3 (GPC3) antibody drug conjugate (ADC) in a hepatocellular carcinoma (HCC) patient derived xenograft (PDX) model was used for evaluation of this proposed model. Our model was able to describe the kinetics of growth inhibition of HCC PDX models following treatment with anti-GPC3 ADC remarkably well. The estimated tumurostatic concentrations were used in tandem with human PKs translated from cynomolgus monkey for prediction of the efficacious dose. The projected efficacious human dose of anti-GPC3 ADC was in the range 0.20–0.63 mg/kg for the Q3W dosing regimen, with a median dose of 0.50 mg/kg. This publication is the first step in evaluating the applicability of GF in PK/PD modeling of ADCs. The authors are hopeful that incorporation of GF will result in an improved translation of the preclinical efficacy of ADCs to clinical settings and thereby better prediction of the efficacious human dose.     

Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension

Key points

• Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.
• Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.
• Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.
• Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abstract

Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H₂O₂; 0.15 mmol l⁻¹). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H₂O₂ promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H₂O₂‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR ventricular myocytes, except with larger EAD amplitude. During the early stages of hypertension, when challenged with oxidative stress, SHR hearts showed an increased ventricular arrhythmogenicity that stems primarily from tissue remodelling (hypertrophy, fibrosis) rather than cellular electrophysiological changes. Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abbreviations

AP

action potential

APD

action potential duration

APD₉₀

action potential at 90% duration

CaMKII

calcium/calmodulin‐dependent protein kinase II

CaT

calcium transient

CaTD₉₀

calcium transient at 90% duration

CI

confidence interval

DBP

diastolic blood pressure

EAD/DAD

early/delayed after‐depolarization

HR

heart rate

ICC

interclass correlation

I_Ca,L

L‐type calcium current

I_Ks

slow delayed rectifier potassium current

I_Na

sodium current

I_to

transient outward potassium current

IVS(d,s) interventricular septum thickness (during diastole

during systole)

LV

left ventricle

LVEF

left ventricular ejection fraction

LVFS

left ventricular fractional shortening

LVH

left ventricular hypertrophy

LVID(d,s) left ventricular internal diameter (during diastole

during systole)

MV

mitral valve

NR

normotensive rats

PA peak vel

pulmonary artery peak velocity

(P)CL

(pacing) cycle length

PW

posterior wall

P‐ECG

pseudo‐electrocardiogram

RV

right ventricle

RWT

relative wall thickness

SHR

spontaneously hypertensive rats

SHHF

spontaneously hypertensive heart failure

SBP

systolic blood pressure

VT/VF

ventricular tachycardia and fibrillation

     

Serum levels of interferon-gamma, tumour necrosis factor-alpha, soluble interleukin-6R and soluble cell activation markers for monitoring response to treatment of leprosy reactions

Identifying pathogen and host-related laboratory parameters are essential for the early diagnosis of leprosy reactions. The present study aimed to clarify the validity of measuring the profiles of serum cytokines [interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha], the soluble IL-6 receptor (sIL-6R), soluble T cell (sCD27) and macrophage (neopterin) activation markers and Mycobacterium leprae-specific anti-PGL-I IgM antibodies in relation to the leprosy spectrum and reactions. Serum samples from 131 Indonesian leprosy patients (82 non-reactional leprosy patients and 49 reactional) and 112 healthy controls (HC) from the same endemic region were investigated. Forty-four (89.8%) of the reactional patients had erythema nodosum leprosum (ENL) while only five (10.2%) had reversal reaction (RR). Follow-up serum samples after corticosteroid treatment were also obtained from 17 of the patients with ENL and one with RR. A wide variability in cytokine levels was observed in the patient groups. However, IFN-gamma and sIL-6R were elevated significantly in ENL compared to non-ENL patients. Levels of IFN-gamma, TNF-alpha and sIL-6R declined significantly upon corticosteroid treatment of ENL. Thus, although the present study suggests limited applicability of serial measurement of IFN-gamma, TNF-alpha and sIL-6R in monitoring treatment efficacy of ENL, reactions it recommends a search for a wider panel of more disease-specific markers in future studies.