Improving glucocorticoid replacement profiles in adrenal insufficiency

There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long‐term benefits is not yet clear. There is a dearth of evidence and high‐quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.     

Racial differences in hemoglobin and plasma volume variation: implications for muscle performance and recovery

Objective: To examine the effect of race differences on sprint performance, Hemoglobin (Hb), Hematocrit (Ht) and plasma volume (PV) variation in response to repeated sprint exercise.

Design: Thirty-six healthy, moderately trained men and women (20.8?±?0.2 year-old) volunteered to participate in this study. They were allocated to one of the four groups according to their gender and race: Black men’s group (BM, n?=?9), White men’s group (WM, n?=?9), Black women’s group (BW, n?=?9) and White women’s group (WW, n?=?9). All participants performed the running-based anaerobic sprint test (RAST), which consists of six?35-m sprints with 10 s of recovery in-between. Six venous blood samples were collected to determine Hb, Ht and PV levels at rest, after warm-up, immediately post- and at 5, 15 and 30 min post-RAST. Blood lactate is also sampled during the 3rd minutes of recovery.

Results: The best running time was significantly shorter (P?=?.002) in BW compared to WW. We have observed significantly higher Hb (P?=?.010) and Ht (P?=?.004) levels in BW compared to WW during the 5th minute of recovery. During RAST, the PV decreased significantly (P?=?.007) in WM only. Black groups had lower (P?<?.05) lactate levels compared to the white subjects. During recovery, PV increase was significantly (P?=?.003) higher in WW compared to BW during the 5th minute of recovery.

Conclusion: This study demonstrated that sprint and repeated sprint performances were different between white and black women. Differences in anaerobic performance between the groups were associated with racial differences in lactate levels and blood count among women’s group during recovery time. Hence, it is important to take into account this race-related difference in hematological parameters in responses to intense efforts.     

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy,with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Background The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT).Methods 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed.Results 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017).Conclusion No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.Subject terms: Breast cancer, Breast cancer     

The BiTE (bispecific T-cell engager) platform: Development and future potential of a targeted immuno-oncology therapy across tumor types

Immuno-oncology therapies engage the immune system to treat cancer. BiTE (bispecific T-cell engager) technology is a targeted immuno-oncology platform that connects patients' own T cells to malignant cells. The modular nature of BiTE technology facilitates the generation of molecules against tumor-specific antigens, allowing off-the-shelf immuno-oncotherapy. Blinatumomab was the first approved canonical BiTE molecule and targets CD19 surface antigens on B cells, making blinatumomab largely independent of genetic alterations or intracellular escape mechanisms. Additional BiTE molecules in development target other hematologic malignancies (eg, multiple myeloma, acute myeloid leukemia, and B-cell non-Hodgkin lymphoma) and solid tumors (eg, prostate cancer, glioblastoma, gastric cancer, and small-cell lung cancer). BiTE molecules with an extended half-life relative to the canonical BiTE molecules are also being developed. Advances in immuno-oncology made with BiTE technology could substantially improve the treatment of hematologic and solid tumors and offer enhanced activity in combination with other treatments.     

类似胆总管囊肿的胆总管横纹肌肉瘤：阻塞性黄疸的罕见原因

肝外胆道肿瘤罕见，其中以横纹肌肉瘤最常见。横纹肌肉瘤是一种软组织恶性肌肉骨骼肿瘤，是儿童非常罕见的一种胆总管恶性肿瘤。它通常表现为阻塞性黄疸和/或瘙痒。如果肿瘤没有局部浸润邻近组织，其影像学表现则类似胆总管囊肿。因此，确诊通常是在手术时或术前通过活检。早期诊断、与胆总管囊肿鉴别、尽早开始治疗对延长患者生存时间有重要意义。该文报道1例10岁男童，反复阻塞性黄疸和发热，术前诊断为胆总管囊肿，术后确诊为胆总管胚胎性横纹肌肉瘤。经手术切除、术后化疗，该患儿预后良好。故必须了解这种罕见的肿瘤可以类似先天性胆总管囊肿，并且在儿童阻塞性黄疸的鉴别诊断时应加以考虑。