The effect of diagnosing Alzheimer’s disease on frequency of physician visits

OBJECTIVE: Two groups of elderly subjects were studied to see whether patterns of visits to physicians changed after one group received the diagnosis of Alzheimer’s disease. DESIGN: Case—control study. SETTING: Health maintenance organization (HMO). PATIENTS/PARTICIPANTS: Two groups of ambulatory subjects (mean age 77 years) were enrolled from an HMO population for this case—control study: 120 cases had probable Alzheimer’s disease diagnosed at enrollment, and another 120 cognitively intact controls with similar comorbidity were enrolled after being frequency-matched for age and gender. Exclusion criteria were nursing home admission and death during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were examined for a four-year period: two years prior to and two years following enrollment and diagnosis. Physician visits declined slightly after enrollment for the persons receiving the diagnosis of Alzheimer’s disease [17.5/2 years prior vs 16.5/2 years after (NS)], whereas visits increased over time for the controls [13.7/2 vs 16.3/2 (p<0.05)], hence the rates were similar after enrollment [16.5 vs 16.3 (NS)]. The proportion of subjects with fewer visits during the period after enrollment was higher among the cases than it was among the controls [54% vs 37%; odds ratio =2.0 (95% confidence interval =1.6, 3.1)]. Hospitalizations and emergency department use did not change significantly after enrollment. CONCLUSIONS: Physician visit frequency was high before, then decreased after, demented patients received their diagnosis, approaching the frequency in a control population without dementia. This phenomenon cannot be accounted for by nursing home placement, comorbidity, or mortality. Increased hospitalization and emergency department use did not ensue after diagnosis.     

Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed.     

CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny

During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I-restricted T cell receptors (TcR) differentiate into CD8⁺ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8-null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I-restricted TcR. In all three instances CD8 was required for positive selection of MHC class I-restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I-restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I-restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule.     

Characteristics and outcome of patients with dual hepatitis B and C‐associated hepatocellular carcinoma: are they different from patients with single virus infection?

Background: Patients with hepatocellular carcinoma (HCC) caused by dual hepatitis B and C virus (HBV, HCV) infection may constitute a distinct disease group that is different from patients with single virus infection. This study compared the clinical characteristics and outcomes of patients with HBV, HCV and dual virus infection. Methods: A prospective database of 1215 HCC patients with chronic hepatitis B, C or dual virus infection was investigated. Results: Patients with HCV infection (n=388) were significantly older (mean age, 69 years) than patients with dual virus (n=75, 65 years) and HBV (n=752; 60 years) infection (P<0.0001). The male‐to‐female ratios for the HBV, dual virus and HCV groups were 5.2, 3.4 and 1.3 respectively (P<0.0001). Patients in the HBV group more often had higher total tumour volume (mean, 409 cm³) than those in the dual virus group (244 cm³) and HCV (168 cm³) group (P<0.0001). No significant differences of the severity of liver cirrhosis, performance status, cancer staging and tumour cell differentiation were noted among the three groups. Patients in the HCV group had a significantly poor survival in comparison with the HBV group only in the subset of patients with small tumour volume (<50 cm³) in the Cox proportional hazards model (relative risk, 1.44; P=0.041). Conclusions: Dual HBV and HCV virus infection does not accelerate the speed of HCC formation in patients with chronic hepatitis B, and appears to have a modified course of carcinogenesis pathway that is diverted away from the biological behaviour of HBV and HCV infection.     

The epidemiology of Clostridium difficile infection in patients with cancer

Introduction: Clostridium difficile infection (CDI) is a significant cause of healthcare-associated diarrhoea, and the emergence of endemic strains resulting in poorer outcomes is recognised worldwide. Patients with cancer are a specific high-risk group for development of infection.

Areas covered: In this review, modifiable and non-modifiable risk factors for CDI in adult patients with haematological malignancy or solid tumours are evaluated. In particular, the contribution of antimicrobial exposure, hospitalisation and gastric acid suppression to risk of CDI are discussed. Recent advances in CDI treatment are outlined, namely faecal microbiota transplantation and fidaxomicin therapy for severe/refractory infection in cancer populations. Outcomes of CDI, including mortality are presented, together with the need for valid severity rating tools customised for cancer populations.

Expert commentary: Future areas for research include the prognostic value of C. difficile colonisation in cancer patients and the potential impact of dedicated antimicrobial stewardship programs in reducing the burden of CDI in cancer units.     

Pure endoscopic resection versus laparoscopic assisted procedure for upper gastrointestinal stromal tumors: Perspective from a surgical endoscopist

Management of upper gastrointestinal (UGI) tract gastrointestinal stromal tumor (GIST) has evolved significantly over the past two decades. For GIST size smaller than 5 cm, laparoscopic resection has become the current standard. To avoid postoperative gastric deformity and preserve gastric function, laparoscopic endoscopic cooperative surgery (LECS) was developed and various modifications have been reported and utilized successfully. Pure endoscopic resection techniques have also been reported at a similar period of time, which further push the boundary of incisionless surgery in managing these lesions. Both tunneling and nontunneling exposed type endoscopic full thickness resection are well described procedures for resection of small UGI GIST. In this review, a summary of these procedures is provided, and the pros and cons of each technique from the perspective of a surgical endoscopist are discussed in detail. LECS and endoscopic resection are complementary to each other. The choice of technique should be tailored to the location, morphology, and size of the target lesions, taking into account the experience of the laparoscopic surgeons and endoscopists.     

H2‐M3‐restricted CD8+ T cells augment CD4+ T‐cell responses by promoting DC maturation

Infection with Listeria monocytogenes triggers the activation and expansion of nonconventional CD8⁺ T cells restricted by the MHC class Ib molecule, H2‐M3. H2‐M3‐restricted CD8⁺ T cells exhibit a memory phenotype, rapidly produce cytokines, and reach peak frequencies sooner than conventional MHC class Ia‐restricted CD8⁺ T cells. In this study, we found that simultaneous in vivo priming of H2‐M3‐restricted T cells and adoptively transferred OT‐II CD4⁺ T cells on the same DC enhances the survival of OT‐II cells. Stimulation of H2‐M3‐restricted T cells were found to induce DC maturation resulting in costimulatory molecule upregulation and production of T_H1‐type cytokines, which was dependent on both cell‐to‐cell contact and soluble factors, particularly TNF‐α, produced by activated H2‐M3‐restricted T cells. Interestingly, H2‐M3‐restricted T cells were more efficient than activated NK cells in inducing DC maturation. Furthermore, we found that OVA_323–339‐coated DC matured by coculturing with peptide‐stimulated H2‐M3‐restricted T cells were more efficient in stimulating the proliferation of Ag‐activated OT‐II cells. This study indicates that H2‐M3‐restricted T cells promote immune responses by CD4⁺ T cells by inducing DC maturation and suggests novel mechanisms for vaccine development.