The primary cause of adrenocortical hypertrophy is increased adrenocorticotrophic hormone (ACTH) stimulation. In toxicology studies, such a condition can arise as a result of the stress response, but it may also occur due to deficient glucocorticoid feedback regulation of ACTH due to toxicity to the adrenal cortex. This latter condition is defined as adrenocortical insufficiency and represents a serious adverse toxic effect on the function of the adrenal cortex. Adrenocortical hypertrophy may occur in the absence of other adrenocortical lesions such that a toxicopathological mechanism is not obvious, for example by pharmacological inhibition of steroidogenesis at the biochemical level. This review discusses the different aetiological factors and mechanisms producing adrenocortical hypertrophy. The need for further evidence in ascribing findings to stress is discussed, as is a protocol for establishing differential diagnoses between stress-induced and toxicity-induced adrenocortical hypertrophy, which is useful in cases where there are no other histopathological lesions in the adrenal cortex. It is concluded that all cases of adrenocortical hypertrophy require further investigation or evidence to ascribe such findings to either stress or adrenocortical inhibition/insufficiency, and that all cases of adrenocortical insufficiency (whether due to a histopathological lesion or reversible pharmacological enzyme inhibition) represent a serious adverse effect that must be properly considered in toxicological risk assessment.
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Background The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. Methods This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. Results 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 RT-PCR positivity. Of the remaining 168 participants, 12/81 (14·8%) CCP and 13/87 (14·9%) control recipients developed SARS-CoV-2 infection; 6 (7·4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25·3 vs. 25·2 days; p = 0·49) and COVID-19 (26·3 vs. 25·9 days; p = 0·35) was similar for both groups. Conclusions Administration of high-titer CCP as post-exposure prophylaxis, while appearing safe, did not prevent SARS-CoV-2 infection.
Cancer is a growing global health issue, and many countries are ill-prepared to deal with their current cancer burden let alone the increased burden looming on the horizon. Growing and aging populations are projected to result in dramatic increases in cancer cases and cancer deaths particularly in low- and middle-income countries. It is imperative that planning begin now to deal not only with those cancers already occurring but also with the larger numbers expected in the future. Unfortunately, such planning is hampered, because the magnitude of the burden of cancer in many countries is poorly understood owing to lack of surveillance and monitoring systems for cancer risk factors and for the documentation of cancer incidence, survival and mortality. Moreover, the human resources needed to fight cancer effectively are often limited or lacking. Cancer diagnosis and cancer care services are also inadequate in low- and middle-income countries. Late-stage presentation of cancers is very common in these settings resulting in less potential for cure and more need for symptom management. Palliative care services are grossly inadequate in low- and middle-income countries, and many cancer patients die unnecessarily painful deaths. Many of the challenges faced by low- and middle-income countries have been at least partially addressed by higher income countries. Experiences from around the world are reviewed to highlight the issues and showcase some possible solutions.
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