The forgotten people: Hepatitis B virus (HBV) infection as a priority for the inclusion health agenda.

Hepatitis B virus (HBV) infection represents a significant global health threat, accounting for 300 million chronic infections and up to 1 million deaths each year. HBV disproportionately affects people who are under-served by health systems due to social exclusion, and can further amplify inequities through its impact on physical and mental health, relationship with stigma and discrimination, and economic costs. The 'inclusion health' agenda focuses on excluded and vulnerable populations, who often experience barriers to accessing healthcare, and are under-represented by research, resources, interventions, advocacy, and policy. In this article, we assimilate evidence to establish HBV on the inclusion health agenda, and consider how this view can inform provision of better approaches to diagnosis, treatment, and prevention. We suggest approaches to redress the unmet need for HBV interventions among excluded populations as an imperative to progress the global goal for the elimination of viral hepatitis as a public health threat.

Utility of Esophageal Ultrasound-guided Biopsy of Mediastinal Lymph Nodes in Diagnosis of Childhood Tuberculosis.

A 6-year-old boy with autistic spectrum disorder was diagnosed with tuberculosis infection following contact tracing of his mother who had isoniazid-resistant pulmonary tuberculosis. He progressed to develop mediastinal lymphadenopathy causing a persistent cough. He was too small to undergo endobronchial ultrasound-guided biopsy. As an alternative, he underwent esophageal endoscopic ultrasound-guided biopsy, leading to confirmation of the diagnosis. We believe this approach to diagnostic biopsy is underrecognized in pediatric practice, and highlight its utility with this case and a brief literature review.

Iron-deficiency anaemia: the perils of excessive milk-drinking.

Iron-deficiency anaemia is a widespread and largely preventable problem in the paediatric population, with numerous potential sequelae. We describe the case of a 2-year-old girl presenting with non-specific symptoms, who was found to be iron-deficient and anaemic, in the context of excessive cow's milk consumption. We explore the patient's diagnostic journey, including a neurological deterioration and the link between her iron deficiency and the final diagnosis.

Screening for infection in unaccompanied asylum-seeking children and young people.

We aimed to evaluate a screening programme for infection in unaccompanied asylum seeking children and young people against national guidance and to described the rates of identified infection in the cohort. The audit was conducted by retrospective case note review of routinely collected, anonymised patient data from all UASC referred between January 2016 and December 2018 in two paediatric infectious diseases clinics.There were 252 individuals from 19 countries included in the study, of these 88% were male, and the median age was 17 years (range 11-18). Individuals from Afghanistan, Eritrea and Albania constituted the majority of those seen. Median time between arriving in the UK and infection screening was 6 months (IQR 4-10 months, data available on 197 UASC). There were 94% (238/252) of cases tested for tuberculosis (TB), of whom 23% (55/238) were positive, including three young people with TB disease. Of those tested for hepatitis B, 4.8% (10/210) were positive, 0.5% (1/121) were positive for hepatitis C and of 252 tested, none were positive for HIV. Of the 163 individuals who were tested for schistosomiasis, 27 were positive (16%).The majority of patients were appropriately tested for infections with a high rate of identification of treatable asymptomatic infection. Infections were of both individual and public health significance. Our findings of clinically significant rates of treatable infections in UASC highlight the importance of infection screening for all in this vulnerable patient group.

B-cell development and pneumococcal immunity in vertically acquired HIV infection.

OBJECTIVES: Many children with HIV infection now survive into adulthood. This study explored the impact of vertically acquired HIV in the era of antiretroviral therapy on the development of humoral immunity. DESIGN: Natural and vaccine-related immunity to pneumococcus and B-cell phenotype was characterized and compared in three groups of young adults: those with vertically-acquired infection, those with horizontally acquired infection and healthy controls. METHODS: Serotype-specific pneumococcal (Pnc) immunoglobulin M and G concentrations before and up to 1 year post-Pnc polysaccharide (Pneumovax) immunization were determined, and opsonophagocytic activity was analysed. B-cell subpopulations and dynamic markers of B-cell signalling, turnover and susceptibility to apoptosis were evaluated by flow cytometry. RESULTS: HIV-infected patients showed impaired natural Pnc immunity and reduced humoral responses to immunization with Pneumovax; this was greatest in those viraemic at time of the study. Early-life viral control before the age of 10 years diminished these changes. Expanded populations of abnormally activated and immature B-cells were seen in both HIV-infected cohorts. Vertically infected patients were particularly vulnerable to reductions in marginal zone and switched memory populations. These aberrations were reduced in patients with early-life viral control. CONCLUSION: In children with HIV, damage to B-cell memory populations and impaired natural and vaccine immunity to pneumococcus is evident in early adult life. Sustained viral control from early childhood may help to limit this effect and optimize humoral immunity in adult life.

Elective endovascular treatment of unruptured intracranial aneurysms: a management case series of patient outcomes after institutional change to admit patients principally to postanesthesia care unit rather than to intensive care.

BACKGROUND: Our intention in this case series was to review the postoperative care and neurologic outcomes of patients who had undergone elective endovascular treatment of unruptured intracranial aneurysms. The case series is unique managerially in that a progressively increasing percentage of patients were admitted to the postanesthesia care unit (PACU; 1:2 nurse-to-patient ratio) and subsequently to the neurosurgical ward (1:3 nurse-to-patient ratio) instead of directly to the intensive care unit (ICU; 1:1 nurse-to-patient ratio). METHODS: A retrospective review was performed of 170 consecutive elective endovascular procedures to treat unruptured intracranial aneurysms between July 2009 and September 2012. Data included patient, aneurysm, procedural characteristics, and adverse events within 96 hours after the procedure. Rates of ICU admission and perioperative neurologic adverse events were compared over time. RESULTS: Although direct ICU admission rates decreased over time (P < 0.0001) from 100% to 15%, perioperative neurologic event rates did not change (P = 0.79). Sixteen of 170 patients experienced perioperative neurologic events. The percentages of patients with neurologic events who died or had deficits that did not resolve before discharge were 38% (3 of 8) among patients directly admitted to the ICU versus 38% (3 of 8) among those first admitted to the PACU. Although the duration of anesthesia was greater among patients admitted to the ICU, duration was not useful in predicting decisions on the day of surgery for individual patients. The duration of anesthesia also was not meaningfully associated with information available preoperatively (i.e., for use when scheduling the case). CONCLUSIONS: In centers in which PACU and ward care are comparable to those in this case series, in the absence of intraoperative events with the potential for ongoing cerebral ischemia, most patients undergoing elective endovascular treatment of unruptured cerebral aneurysms can be managed without direct ICU admission. Scheduling all these procedures by using the mean historical anesthesia duration is reasonable.

Spinal tuberculosis in children.

OBJECTIVES: To review our experience of spinal tuberculosis (TB) at a major UK paediatric tertiary referral centre. METHODS: The authors performed a retrospective case survey of 21 patients admitted to Great Ormond Street Hospital over a 15-year period (1995-2010) with confirmed or presumed spinal TB. Data were collected concerning demographics, clinical, laboratory and radiological characteristics, treatment and clinical outcome. RESULTS: Only one patient was of Caucasian origin. Four (19%) had a previous diagnosis of TB, 11 (52%) a known contact, 10 (48%) had received BCG vaccine and none were HIV-positive. Clinical presentations included systemic symptoms (18 patients), back pain (16 patients), deformity (five patients) and neurological deficits (12 patients). Mycobacterium tuberculosis was isolated from 14 patients (67%) including one multi-drug resistant strain. Spinal cord compression or critical stenosis was demonstrated in eight patients (38%). All received TB treatment for at least 12 months; six patients received treatment for a longer period. Seven (33%) underwent surgical intervention. Seventy-five per cent showed clinical and radiological resolution after treatment. No patients died or suffered long-term neurological deficit. CONCLUSIONS: Spinal TB in children needs a high index of suspicion for diagnosis. Early referral to an expert centre allows a multidisciplinary approach to management. The authors recommend that treatment should be individually tailored and may need to exceed 12 months in cases of poor adherence, extensive disease or drug resistance.

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation.

BACKGROUND AIMS: Granulocyte-macrophage (GM) colony-stimulating factor (CSF) has been used as an adjuvant in cancer immunotherapy. We tested the hypothesis that GM-CSF (Leukine(®); sargramostim) improves immune reconstitution after hematopoietic stem cell transplantation (HSCT) based on our prior in vitro work that demonstrated the pro-inflammatory effects of GM-CSF on dendritic cells (DC). METHODS: GM-CSF was administered to donors, along with standard granulocyte (G) CSF, during stem cell mobilization, and to recipients from the day prior to transplant until engraftment. Eighteen patients consented to the GM-CSF(+) protocol and were compared with 17 matched controls undergoing HSCT during the same time period (GM-CSF(-)). RESULTS: Numbers of white blood cells (WBC) and CD34(+) stem cells in the graft were comparable to controls. Surprisingly, contrary to our hypothesis, the allogeneic donor graft had significantly decreased numbers of CD3(+) T cells and their subsets (CD4(+), CD4(+) CD45RA(+), CD4(+) CD45RO(+), CD8(+) and CD8(+) CD45RO(+)), DC (both myeloid and plasmacytoid) and natural killer (NK) cells (CD16(+) CD56(+)). In the GM-CSF arm, following allogeneic transplantation, the levels of DC, T cells and NK cells did not increase with treatment. Conversely, autologous transplant patients receiving GM-CSF had a higher proportion of DC at the time of engraftment. CONCLUSIONS: These findings demonstrate that administration of GM-CSF improves DC reconstitution after autologous rather than allogeneic HSCT.

Dendritic cells as therapeutic agents against cancer.

Dendritic cells (DC) are antigen-presenting cells whose immunobiology has been proven to be central to the function of the immune system. Further understanding of these cells is leading the way to the manipulation of the immune system as a tool to cure and prevent a vast array of diseases including cancers. These cells have been used in trials as vaccine adjuvants in therapies that aim to break the body's tolerance to the tumor. From the first 1000 DC vaccinees in 2003 there has been a breadth of information on safety that is paving the way to the study of the efficiency of these therapies. This review aims to explore recent updates to the current literature on DC vaccine therapies in clinical trials and analyze their future. At this crossroads is where intricacies of the technique are being revised to explore the most efficient and effective parameters for the enhancement of DC adjuvant therapies.

Factors associated with improved outcome after surgery in metastatic breast cancer patients.

BACKGROUND: Recent studies suggest local surgical therapy improves survival in metastatic breast cancer (MBC). We evaluate the difference in outcome in patients with MBC after mastectomy versus breast conservation (BCT) and factors that influence outcome. METHODS: In a retrospective review of our prospective database, we identified patients who presented with MBC (1990 to 2007). Patient surgery type and clinicopathologic factors were reviewed. We compared OS between pts dependent on surgery and clinicopathologic factors. RESULTS: Of the 566 patients with MBC, 154 (27%) underwent removal of the primary tumor. Surgery was associated with an improved OS (33%) versus no surgery (20%) (P = 0.0015). Of those undergoing local therapy; mastectomy was associated with a 37% OS vs BCT with a 20% OS (P = 0.04). CONCLUSIONS: Our study confirms that removal of the primary tumor in MBC is associated with improved overall survival. It appears that mastectomy is associated with a significantly improved overall survival.

Supplemental tibial fixation for anterior cruciate ligament reconstruction.

This report describes transosseous backup suture fixation for anterior cruciate ligament (ACL) grafts of all varieties, used to distally augment proximal screw fixation in the tibia. Using a simple suture configuration, this method secures the ACL graft to the tibial cortex in conjunction with a proximal interference screw. The technique is applicable for all graft configurations, including allograft, autograft, bone, and both 2- and 4-strand soft-tissue grafts. The described technique is intended to be used for secondary or backup fixation of the graft in the tibial tunnel and not as primary fixation. This construct can be reproducibly created, making use of the sutures that are typically present on the graft after the interference screw is placed. This technique for backup tibial fixation precludes the need for external hardware, which in many instances may be symptomatically proud. Furthermore, use of this technique may represent a potential cost savings because no additional devices or equipment is used or purchased. This technique is simple, fast, and inexpensive, making use of available constructs to enhance the security of graft fixation during ACL reconstruction.

An effective electronic surgical referral system.

INTRODUCTION: Electronic booking of out-patient appointments is being rolled out in England under the 'Choose and Book' programme. We set up and ran a local electronic surgical referral service before this. This paper assesses the effect of the electronic surgical referral service on patient waiting times and attendance rates. PATIENTS AND METHODS: The study included 54 patients referred electronically and 189 referred on paper to a single colorectal surgical service over the same period. RESULTS: The appointment booking was achieved on the same day as the referral was made for the majority of electronic referrals whereas it took an average of 7 days for paper referrals. There was no significant difference in the time from referral to being seen in clinic between the two groups. Patients referred electronically were much more likely to attend for their appointment. CONCLUSIONS: This study shows that an electronic surgical referral system can improve efficiency. This may be because this system allows enhanced patient choice of appointment date and time.