Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma

This article provides an overview of the pathology of Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma, highlighting its unique morphology and clinical features. Lymphoepithelioma-like gastric carcinoma is a rare neoplasm of the stomach with a better prognosis than conventional adenocarcinoma. Most lymphoepithelioma-like gastric carcinomas are associated with EBV infection, while a subset is associated with microsatellite instability. Even though there is a very strong association with EBV, its exact role in carcinogenesis still remains to be elucidated in those cancers that harbor EBV. Distinctive histology and demonstration of EBV using in situ hybridization, polymerase chain reaction, or Southern blotting and immunohistochemistry for the DNA mismatch repair genes or polymerase chain reaction analysis of microsatellite loci to assess microsatellite instability helps to make the diagnosis.     

The impact of chronic illness on workforce participation and the need for assistance with household tasks and personal care by older Australians

People, along with their families, feel the impact of chronic illness in many areas of their lives. It has been known that those with chronic illness leave the workforce earlier than their peers, have lower incomes and often need additional support to manage their health and lives. However, limited information is available about whether chronic illness is already present prior to retirement, or has developed subsequently. Similarly, we know little about what personal and household assistance is needed by people with chronic illness. In this study, a random sample of 10 000 members of National Seniors Australia, stratified by age and state of residence, were surveyed by post between August and September 2009 and asked about their chronic illnesses along with their age at diagnosis. In addition, participants were asked about their need for assistance with everyday household tasks and personal care. Responses were received from 4574 respondents, a response rate of 45.7%. Of those responding, 82.2% reported having at least one chronic illness at the time of the survey. The study confirms that ill health leads to earlier retirement from the workforce, and those who are sickest require more assistance with their household tasks and personal care. Each additional chronic illness present at age 50 reduced working life by a year, and each present at age 60 by 0.7 years. Diabetes, arthritis and depression were significantly related to earlier retirement. The impact was greatest for both continued workforce participation and need for assistance for those suffering from depression or anxiety. The relationships between health, workforce participation and need for assistance in daily activities are complex. Further research is required to uncover this complexity; nevertheless, the findings highlight the need to review the adequacy of current social and health policy for this particular population.     

Precision oncology using a clinician‐directed,tailored approach to molecular profiling

1 Aim

Precision oncology involves molecularly matching patients to targeted agents usually in early drug development (EDD) programs. Molecular profiling (MP) identifies actionable targets. Comprehensive commercial MP platforms are costly and in resource limited environments, a more practical approach to MP is necessary to support EDD and precision oncology. We adopted a clinician‐directed, tailored approach to MP to enrol patients onto molecularly targeted trials. We report the feasibility of this approach.

2 Methods

All patients referred to the Royal Melbourne Hospital (RMH) EDD between September 2013 and September 2015 were identified in a prospective database. Key captured data included clinicopathological data, MP platform ordered (if any), molecular targets identified and subsequent enrolment onto clinical trials. EDD‐clinician decisions to order MP and the platform utilized was guided by patient consultation, tumor type, trial availability and requirement for molecular information.

3 Results

We identified 377 patients referred to RMH EDD. A total of 216 (57%) had MP ordered. The remainder had known actionable targets (19%), or were inappropriate for clinical trials (24%). In those undergoing MP, 187 genetic aberrations were found in 113 patients with 98 considered actionable targets in 86 patients. Ninety‐eight (25%) patients were enrolled onto a clinical trial, including 40 (11%) receiving molecularly matched treatments. Median progression‐free survival was improved in patients enrolled onto molecularly matched trials compared to those on unmatched trials (3.6 months vs 1.9 months, HR 0.58 [0.38–0.89], P  =  0.013).

4 Conclusion

A clinician‐directed, tailored approach to the use of MP is feasible, resulting in 11% of patients enrolled onto molecularly matched trials.     

Beteiligung des peripheren Nervensystems bei Morbus Crohn

Periphere neurologische St?rungen werden in der Literatur nur in Einzelf?llen in direktem Zusammenhang mit Morbus Crohn beschrieben. Wir berichten über zwei Patienten mit Morbus Crohn, die zum einen ein akutes Guillain-Barré-Syndrom (GBS) und zum anderen eine Polyneuropathie sowie eine Myositis entwickelten. Bei einer 65j?hrigen Patientin wurde ca. zwei Wochen nach Beginn eines schweren akuten Guillain-Barré-Syndrom erstmals ein Morbus Crohn mit einer h?morrhagischen Kolitis festgestellt. Die jeweils spezifische Therapie führte binnen weniger Wochen zu einer guten Besserung. Eine 45j?hrige Frau litt seit ca. 12 Jahren an einem Morbus Crohn. Sie entwickelte innerhalb von 8 Wochen eine schwere sensomotorische axonal-demyelinisierende Polyneuropathie und eine granulomat?se Myositis. Ihre Beschwerden zeigten unter Steroiden einen stetigen Rückgang. Unsere Beobachtungen sowie die Literaturübersicht zeigen, da? schwere Polyneuropathien und das GBS in seltenen F?llen mit einer chronisch entzündlichen Darmerkrankungen vergesellschaftet sein k?nnen und somit zu den m?glichen extraintestinalen Manifestationen des Morbus Crohn gez?hlt werden k?nnen.     

Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers

Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (−)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (−)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (−)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (−)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (−)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (−)-(R)-PQ may have a better safety margin than the racemate in human.     

Fiber loop ringdown DNA and bacteria sensors

We report a new type of refractive index-based biosensor using a fiber loop ringdown evanescent field (FLRD-EF) sensing scheme, in which the sensing signal is a time constant and detection sensitivity is enhanced by the multipass nature of the ringdown technique. Bulk index-based detections of three different single strand DNAs and one type of bacteria are demonstrated for the FLRD-EF sensors that utilize a partially-etched single mode fiber as the sensor head. Stepwise coating of the sensor head with poly-L-lysine and a probe DNA has enabled surface index-based label-free target DNA sensing. We expect an array of FLRD-EF biosensors to be created, which are superior to counterparts in terms of simplicity, low cost, and high sensitivity.     

Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

Background  

Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease.     

Hyperemesis gravidarum and fetal gender: a retrospective study

This retrospective study of 9,980 women who delivered at the James Paget Hospital, Norfolk, UK, over 5 years, aimed to primarily determine whether the incidence of hyperemesis gravidarum (HG) is higher in the presence of a female fetus. The results showed that more women with HG had a female fetus compared with women without HG. Also found was that heavy ketonuria was more prevalent in women with a female fetus compared with women with a male fetus, and the mean number of admissions per woman was also higher in women with a female fetus compared with women with a male fetus. It can be concluded that women presenting with HG are more likely to have a female fetus and that women with HG and a female fetus tend to a higher level of ketonuria and an increased number of hospital admissions.