Acute leukemia in idiopathic sideroblastic anemia: response to combination chemotherapy

Three patients with idiopathic sideroblastic anemia of variable duration developed acute leukemia. In two the leukemia was morphologically and histochemically myeloblastic, in one lymphoblastic. With combination chemotherapy remission was achieved in all three. The remission inductions were complicated by long periods of bone marrow suppression and the duration of remissions was brief (3, 2 and 3 months). Survival after diagnosis was 13, 10 and 9 mo, respectively. The ring sideroblast abnormality persisted during the leukemic and remission phases and transfusion requirements remained unaltered in the two patients with transfusion dependent anemia throughout their courses.     

Towards a combined prognostic index for survival in HIV infection: the role of ‘non‐HIV’ biomarkers

Background

As those with HIV infection live longer, ‘non‐AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non‐HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).

Methods

Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV‐infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS‐defining conditions); ‘non‐HIV’ biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data.

Results

Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle‐aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and ‘non‐HIV’ markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68–0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30‐day C statistic 0.86, 95% confidence interval (CI) 0.80–0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72–0.74). Results were robust to adjustment for missing data.

Conclusions

When added to HIV biomarkers, ‘non‐HIV’ biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.     

Advances in the field of nanooncology

Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important chapter of nanomedicine. Nanobiotechnology has refined and extended the limits of molecular diagnosis of cancer, for example, through the use of gold nanoparticles and quantum dots. Nanobiotechnology has also improved the discovery of cancer biomarkers, one such example being the sensitive detection of multiple protein biomarkers by nanobiosensors. Magnetic nanoparticles can capture circulating tumor cells in the bloodstream followed by rapid photoacoustic detection. Nanoparticles enable targeted drug delivery in cancer that increases efficacy and decreases adverse effects through reducing the dosage of anticancer drugs administered. Nanoparticulate anticancer drugs can cross some of the biological barriers and achieve therapeutic concentrations in tumor and spare the surrounding normal tissues from toxic effects. Nanoparticle constructs facilitate the delivery of various forms of energy for noninvasive thermal destruction of surgically inaccessible malignant tumors. Nanoparticle-based optical imaging of tumors as well as contrast agents to enhance detection of tumors by magnetic resonance imaging can be combined with delivery of therapeutic agents for cancer. Monoclonal antibody nanoparticle complexes are under investigation for diagnosis as well as targeted delivery of cancer therapy. Nanoparticle-based chemotherapeutic agents are already on the market, and several are in clinical trials. Personalization of cancer therapies is based on a better understanding of the disease at the molecular level, which is facilitated by nanobiotechnology. Nanobiotechnology will facilitate the combination of diagnostics with therapeutics, which is an important feature of a personalized medicine approach to cancer.     

Antiviral activity and safety of aplaviroc,a CCR5 antagonist,in combination with lopinavir/ritonavir in HIV‐infected,therapy‐naïve patients: results of the EPIC study (CCR100136)*

Background

This phase IIb study explored the antiviral activity and safety of the investigational CC chemokine receptor 5 (CCR5) antagonist aplaviroc (APL) in antiretroviral‐naïve patients harbouring R5‐ or R5X4‐tropic virus.

Methods

A total of 191 patients were randomized 2:2:2:1 to one of three APL dosing regimens or to lamivudine (3TC)/zidovudine (ZDV) twice daily (bid), each in combination with lopinavir/ritonavir (LPV/r) 400 mg/100 mg bid. Efficacy, safety and pharmacokinetic parameters were assessed.

Results

This study was terminated prematurely because of APL‐associated idiosyncratic hepatotoxicity. A total of 141 patients initiated treatment early enough to have been able to complete 12 weeks on treatment [modified intent‐to‐treat (M‐ITT) population]; of these, 133 completed the 12‐week treatment phase. The proportion of subjects in the M‐ITT population with HIV‐1 RNA <400 copies/mL at week 12 was 50, 48, 54 and 75% in the APL 200 mg bid, APL 400 mg bid, APL 800 mg once a day (qd) and 3TC/ZDV arms, respectively. Similar responses were seen in the few subjects harbouring R5X4‐tropic virus (n=17). Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated nonlinear pharmacokinetics with high interpatient variability.

Conclusions

While target plasma concentrations of APL were achieved, the antiviral activity of APL+LPV/r did not appear to be comparable to that of 3TC/ZDV+LPV/r.     

Intentional paediatric poisoning presentations to emergency departments during the COVID-19 pandemic

Objective

To characterise paediatric poisoning presentations to EDs and determine if the advent of the COVID-19 pandemic was associated with increased intentional paediatric poisoning presentations.

Methods

We performed a retrospective analysis of paediatric poisoning presentations to three EDs (two regional and one metropolitan). Simple and multiple logistic regression analysis were performed to determine the association between COVID-19 and intentional poisoning events. In addition, we calculated the frequency with which patients reported various psychosocial risk factors as being an implicating factor in engaging in an intentional poisoning event.

Results

A total of 860 poisoning events met inclusion criteria during the study period (January 2018–October 2021), with 501 being intentional, and 359 unintentional. There was an increased proportion of intentional poisoning presentations during the COVID-19 pandemic (261 intentional and 218 unintentional in the pre-COVID-19 period vs 241 intentional and 140 unintentional during the COVID-19 period). In addition, we found a statistically significant association between intentional poisoning presentations and an initial COVID-19 lockdown (adjusted odds ratio 26.32, P < 0.05). ‘The COVID-19 lockdown’ or ‘COVID-19’ was reported to be implicating factor for psychological stress in patients who presented with intentional poisonings during the COVID-19 pandemic.

Conclusions

Intentional paediatric poisoning presentations increased during the COVID-19 pandemic in our study population. These results may support an emerging body of evidence that the psychological strain of COVID-19 disproportionately impacts adolescent females.     

Knowledge of ethical lapses and other experiences on clinical licensure examinations.

While clinical licensure examinations claim to protect the public from incompetent practitioners, serious problems related to issues of validity, reliability, and ethics have been reported. The ethical lapses are difficult to document, and reports of problems have been strictly anecdotal. This study's primary purpose was to verify those anecdotal reports by mailing a twenty-one-item survey to a national random sample of one thousand general dentists who graduated from a United States-accredited dental school between 1980 and 1994. For those who responded (42.9 percent) results show that 23.9 percent did not arrange for follow-up care for the patient even though it was indicated. Eight percent reported knowledge of instances where a lesion was intentionally created; 19.3 percent knew of premature treatment provided for purposes of the examination; 13.7 percent knew of a colleague who coerced a patient into accepting treatment; 32.5 percent reported knowledge of unnecessary radiographs. About half of all respondents agreed that the examination was not an accurate assessment of ability, and a similar proportion doubted that human patients were necessary. A more reliable and valid assessment strategy that does not jeopardize patient care is needed.     

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

A Laboratory Investigation into Oviposition Responses of Aedes aegypti to Some Common Household Substances and Water from Conspecific Larvae

Background

The surveillance of Dengue vector – Aedes aegypti, is routinely done by using ovitraps (a dark container filled with water and a wooden paddle/towel cloth provided as a oviposition substrate), which indicates the extent of Aedes activity in an area.

Method

The study evaluated the oviposition responses of laboratory bred gravid Aedes aegypti to commonly available household substances by use of ovitrap method.

Results

Oviposition avoidance or deterrence was exhibited by gravid Aedes to ovitraps baited with salt, fenugreek, vinegar, lime juice, hibiscus leaves, radish and curry leaves, whereas positive oviposition response was noticed to waters from conspecific (of the same species) larvae and cumin seeds baited ovitraps.

Conclusion

The study findings may be utilized by researchers for further chemical analysis of the active ingredients of the substances found promising with a view to explore the possibility of their use by community and individuals for Aedes surveillance and control.Key Words: Aedes, Dengue, Oviposition deterrence/attraction