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Mairi W Lucas,1 Catherine M Kelly2 1Royal College of Surgeons in Ireland, St Stephen’s Green, Dublin, Ireland; 2Mater Private Hospital, Dublin, IrelandCorrespondence: Catherine M Kelly, Consultant Medical Oncologist, UCD Clinical Professor, Mater Private Hospital, Eccles Street, Dublin, Ireland, Email Catherine.kelly@ucd.ieAbstract: The neoadjuvant setting provides immense opportunities for translational research and drug development. The acceptance of pathological complete response (pCR) as a surrogate endpoint for clinical benefit has led to the widespread use of neoadjuvant treatment. Optimal neoadjuvant therapies are determined based on their ability to achieve the highest rates of pCR. Predicted rates of pCR for triple negative breast cancer (TNBC) treated with sequential taxane/anthracycline regimens range from 35% to 48%. With the addition of a platinum agent pCR rates of 55% are predicted. Further increases have been observed with the addition of immune checkpoint inhibitors to this standard chemotherapy backbone. In the pivotal KEYNOTE-522 clinical trial pCR rates of 65% and 69% were reported for chemotherapy plus pembrolizumab in the overall and PD-L1-positive subgroup respectively. The role of the neoadjuvant chemotherapy is less clear in hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer. In general, HR–positive cancers have the least chance of achieving a pCR after neoadjuvant chemotherapy, especially if they are low-grade. If neoadjuvant chemotherapy is given for high-risk HR-positive, HER2-negative breast cancer, standard adjuvant anthracycline/taxane regimens are appropriate. Optimum endocrine therapy is the standard-of-care in the adjuvant setting regardless of pCR. There are several genomic signatures available to guide decisions regarding adjuvant chemotherapy use however these assays are not routinely used in the neoadjuvant setting. For high-risk patients meeting the criteria for the monarchE trial adjuvant abemaciclib in addition to endocrine therapy is associated with an improvement in disease free survival (DFS) at 3 years. Based on the OlympiA trial patients with germline BRCA mutations should be considered for adjuvant olaparib therapy. In this article we review neoadjuvant clinical trials that guide optimum treatment options for TNBC and HR-positive, HER2-negative breast cancer.Keywords: neoadjuvant, pathological complete response, platinum agents, immune checkpoint inhibitors, PARP inhibitors, endocrine therapy

Abstract We studied a previously almost unknown nocturnal mammal, an apparently undescribed species of tree hyrax (Dendrohyrax sp.) in the moist montane forests of Taita Hills, Kenya. We used thermal imaging to locate tree hyraxes, observe their behavior, and to identify woody plants most frequently visited by the selective browsers. We also documented acoustic behavior in forest fragments of different sizes. Data on calling type and frequency were analyzed together with lidar data to estimate population densities and to identify forest stand characteristics associated with large populations. Viable populations were found only in the largest forest fragments (> 90 ha), where tree hyraxes preferred most pristine forest stands with high, multilayered canopies. The estimated population sizes in smaller forest fragments were very limited, and hyraxes were heard to call only during late night and early morning hours, presumably in order to avoid detection. While we frequently recorded tree hyrax songs in the largest forest fragments, we almost never heard songs in the small ones. All remaining subpopulations of the Taita tree hyrax are under threat of human disturbance and further habitat deterioration. Conservation efforts should include protection of all remaining habitat patches, but also reforestation of former habitat is urgently needed.

Anthrax caused by Bacillus anthracis is an old and neglected zoonosis that continues to raise concerns in Southern Africa. In this study, twenty (20) slides with suspected isolates of B. anthracis from anthrax cases between 1990 and 2014 and two (2) from that of a vaccine strain were analysed using MLVA with 15 VNTRs and CanSNPs test. The results from the CanSNPs indicate that all anthrax outbreaks in Zambia between 1990 and 2014 were caused by the lineage A.Br.005/006 of the clade A. This indicates a common ancestral origin of the B. anthracis circulating in the country. This data has described several environmental, wildlife, livestock and human cases that occurred in a 24 year period, from the major areas where anthrax is endemic. The molecular characterization of isolates from anthrax outbreaks in Zambia has revealed a genetic structure in agreement with previous studies from neighbouring countries. Further studies are needed to elucidate how to better manage anthrax outbreaks and define the risk maps of Zambia.

Background: In phase 1-2 trials in patients with resectable, macroscopic stage III melanoma, neoadjuvant immunotherapy was more efficacious than adjuvant immunotherapy., Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab. Only patients in the neoadjuvant group with a partial response or nonresponse received adjuvant treatment. The primary end point was event-free survival., Results: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% in patients in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of patients in the neoadjuvant group and in 14.7% in the adjuvant group., Conclusions: Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.)., (Copyright © 2024 Massachusetts Medical Society.)

Neoadjuvant immune-checkpoint inhibition is a promising emerging treatment approach for patients with surgically resectable macroscopic stage III melanoma. The neoadjuvant setting provides an ideal platform for personalized therapy owing to the very homogeneous nature of the patient population and the opportunity for pathological response assessments within several weeks of starting treatment, thereby facilitating the efficient identification of novel biomarkers. A pathological response to immune-checkpoint inhibitors has been shown to be a strong surrogate marker of both recurrence-free survival and overall survival, enabling timely analyses of the efficacy of novel therapies in patients with early stage disease. Patients with a major pathological response (defined as the presence of ≤10% viable tumour cells) have a very low risk of recurrence, which offers an opportunity to adjust the extent of surgery and any subsequent adjuvant therapy and follow-up monitoring. Conversely, patients who have only a partial pathological response or who do not respond to neoadjuvant therapy still might benefit from therapy escalation and/or class switch during adjuvant therapy. In this Review, we outline the concept of a fully personalized neoadjuvant treatment approach exemplified by the current developments in neoadjuvant therapy for patients with resectable melanoma, which could provide a template for the development of similar approaches for patients with other immune-responsive cancers in the near future., (© 2023. Springer Nature Limited.)

Primary and secondary adrenal insufficiency (AI) are commonly known immune-related adverse events following treatment with immune checkpoint inhibitors (ICIs), and are clinically relevant due to their morbidity and potential mortality. For this reason, upfront identification of patients susceptible for ICI-induced AI could be a step in improving patient's safety. Multiple studies have focused on the identification of novel biomarkers for ICI-induced AI, including autoantibodies, which may be involved in ICI-induced AI as a result of the T-cell-mediated activation of autoreactive B cells. This review highlights the currently described autoantibodies that may be involved in either primary [e.g. anti-21-hydroxylase, anti-17α-hydroxylase, anti-P450scc, anti-aromatic L-amino acid decarboxylase (AADC), anti-interferon (IFN)α and anti-IFNΩ] or secondary AI [e.g. anti-guanine nucleotide-binding protein G(olf) subunit alpha (GNAL), anti-integral membrane protein 2B (ITM2B), anti-zinc finger CCHC-type containing 8 (ZCCHC8), anti-pro-opiomelanocortin (POMC), anti-TPIT (corticotroph-specific transcription factor), anti-pituitary-specific transcriptional factor-1 (PIT-1) and others], and discusses the current evidence concerning their role as biomarker for ICI-induced AI. Standardized autoantibody measurements in patients (to be) treated with ICIs would be a clinically accessible and patient-friendly screening method to identify the patients at risk, and could change the management of ICI-induced AI., (© 2023 The Authors.)

Despite meaningful, incremental improvements in detection, local treatment and adjuvant systemic treatments for breast cancer, there remains a significant risk of late relapse in hormone receptor (HR)-positive disease. 5 years of tamoxifen or an aromatase inhibitor for all patients with HR-positive early breast cancer is considered standard; however, there are now data to support an extended approach using up to 10 years of treatment. This review will provide some historical background on endocrine therapy and summarize the key clinical trials that demonstrate the small absolute benefit of extended adjuvant therapy. We provide suggested treatment algorithms for both premenopausal and postmenopausal patients and an overview of ongoing adjuvant trials.

Background: In the overall spectrum of plastic surgery, hair transplantation for females still plays a marginal role. Previously applied standard methods (standard grafts) could not produce aesthetically satisfying results, so that many female patients who could have benefitted from an operation were discouraged from doing so. It was not until the method of using minigrafts exclusively to cover large areas of androgenetic alopecia in men was developed that acceptable treatment possibilities were also made available to women., Objective: The main applications of hair transplantation for females are: androgenetic alopecia, hereditary changes in the hairline, traumatic alopecia, and cosmetic indications., Methods: Since 1986 all female patients were exclusively treated with mini- and micrografts in one to two or three sessions., Results: Performing hair transplantation calls for a high degree of sensitivity on the part of the surgeon with respect to the woman and her expectations., Conclusion: With the mini- and micrograft technique new aspects in hair transplantation for females can be offered.

Background: In hair transplantation, the availability of a limited number of grafts for a conventional transplantation can pose a serious problem. The result can be a so-called "bunch" or "brush" appearance in the recipient area., Objective: We therefore developed a new method that allows this effect to be minimized., Method: This method is based on the use of a punch (1.6-1.7 mm in diameter) that allows small grafts to be extracted from already established standard grafts. We then transplant the resulting minigrafts in between the established standard grafts, which have now decreased in size., Results: The immediate reduction in the size of the standard grafts and the simultaneous generation of minigrafts produce the desired result: the "minigraft exclusively" look., Conclusion: Thus, patients with previously poor results in standard hair transplantation can now benefit from the modern method of mini- and micrograft transplantation.

Mini- and micrografts produce esthetic results in the treatment of alopecia androgenetica which cannot be achieved using conventional methods. It is for this reason that they should be used exclusively. Their fineness furthermore opens up new vistas in plastic reconstructive surgery, making treatments possible which were previously inconceivable.

With regard to the treatment of alopecia, the so-called bunch effect and the creation of an abrupt hair line are a major problem of the conventional method of hair transplantation. Employing a recently developed technique, autologous miniature grafts bearing 3-4 or 5-6 hair follicles are implanted into randomly distributed recipient punch holes. By means of this technique, we are able to achieve aesthetically acceptable hair growth even after a single operating session.

With the conventional hair transplantation method of Okuda-Orentreich, the tuft effect and the creation of an abrupt hairline have been major problems. In the method presented here, minigrafts are exclusively distributed and transplanted over the entire surface. Through the use of this technique a more aesthetic pattern of hair growth is achieved than was possible before, even after only one treatment.