Prostate specific membrane antigen PET avidity in a granular cell tumour of the left supraspinatus muscle: a case report.

Granular cell tumour is a rare, mostly benign, soft tissue, neuroectodermal tumour, most commonly seen in the skin and peripheral soft tissue. There are no publications to date of PSMA-PET avidity in a granular cell tumour. In this 60 year old male, staging PSMA-PET for a localized intermediate risk prostate cancer incidentally identified a PSMA-avid left supraspinatus lesion, which was subsequently biopsy-proven as a granular cell tumour. We present the first case of PSMA-avid granular cell tumour and add to the growing literature documenting PSMA-PET avidity in benign and malignant lesions apart from prostate cancer.

Medial Epicanthoplasty with the Skin Re-Draping Technique: Technical Refinements for Predictable outcomes.

The epicanthus is a common feature of the Asian eyes. A prominent medial epicanthal fold gives the impression of a blunted affect and the procedure for its removal, the medial epicanthoplasty, is a very commonly requested by Asian patients. This may be performed as an isolated procedure or more commonly in combination with the upper blepharoplasty. Many conventional medial epicanthoplasty techniques are based on skin flaps transposition and excisions, usually variations of the V-Y, W or Z-plasties (1-4). While these have been variably successful at correcting the epicanthal fold, the common problem is significant scarring in the medial canthal and lower eyelid regions (5-8). This is particularly problematic in Asian patients with greater tendencies for hypertrophic scarring and scar hypo or hyper-pigmentation (9). Recently, the skin re-draping method, designed with incisions limited within the margins of the medial canthus and precise and targeted disruption of the underlying fibromuscular tissues, has emerged as the preferred surgical technique for many Asian surgeons because of its effectiveness and superior aesthetic outcomes(6, 10-12). This technique delivers the most inconspicuous incisions and is advantageous because it is effective in eliminating epicanthal folds of various severities. Precise execution of this technique is difficult, given the complex 3-dimensional anatomy of the epicanthus. This paper presents a detailed explanation of surgical concepts of the skin re-draping epicanthoplasty and provide a step-by-step guide to performing this procedure in a safe and effective manner.

Automatic and real-time tissue sensing for autonomous intestinal anastomosis using hybrid MLP-DC-CNN classifier-based optical coherence tomography.

Anastomosis is a common and critical part of reconstructive procedures within gastrointestinal, urologic, and gynecologic surgery. The use of autonomous surgical robots such as the smart tissue autonomous robot (STAR) system demonstrates an improved efficiency and consistency of the laparoscopic small bowel anastomosis over the current da Vinci surgical system. However, the STAR workflow requires auxiliary manual monitoring during the suturing procedure to avoid missed or wrong stitches. To eliminate this monitoring task from the operators, we integrated an optical coherence tomography (OCT) fiber sensor with the suture tool and developed an automatic tissue classification algorithm for detecting missed or wrong stitches in real time. The classification results were updated and sent to the control loop of STAR robot in real time. The suture tool was guided to approach the object by a dual-camera system. If the tissue inside the tool jaw was inconsistent with the desired suture pattern, a warning message would be generated. The proposed hybrid multilayer perceptron dual-channel convolutional neural network (MLP-DC-CNN) classification platform can automatically classify eight different abdominal tissue types that require different suture strategies for anastomosis. In MLP, numerous handcrafted features (∼1955) were utilized including optical properties and morphological features of one-dimensional (1D) OCT A-line signals. In DC-CNN, intensity-based features and depth-resolved tissues' attenuation coefficients were fully exploited. A decision fusion technique was applied to leverage the information collected from both classifiers to further increase the accuracy. The algorithm was evaluated on 69,773 testing A-line data. The results showed that our model can classify the 1D OCT signals of small bowels in real time with an accuracy of 90.06%, a precision of 88.34%, and a sensitivity of 87.29%, respectively. The refresh rate of the displayed A-line signals was set as 300 Hz, the maximum sensing depth of the fiber was 3.6 mm, and the running time of the image processing algorithm was ∼1.56 s for 1,024 A-lines. The proposed fully automated tissue sensing model outperformed the single classifier of CNN, MLP, or SVM with optimized architectures, showing the complementarity of different feature sets and network architectures in classifying intestinal OCT A-line signals. It can potentially reduce the manual involvement of robotic laparoscopic surgery, which is a crucial step towards a fully autonomous STAR system.

Long-term outcomes of definitive radiation with volumetric modulated arc therapy and concurrent chemotherapy for squamous cell carcinoma of the anus in a regional Australian cancer centre.

INTRODUCTION: Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long-term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines. METHODS: All consecutive patients treated with the VMAT technique for curative-intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan-Meier estimates of locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were obtained. RESULTS: In total, 44 patients were analysed. The median follow-up was 48.9 months (Range 7.8-107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan-Meier estimates for locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment-related deaths. The 5 -year colostomy-free survival rate was 86.4%. CONCLUSION: Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes.

Small RNA Changes in Plasma Have Potential for Early Diagnosis of Alzheimer's Disease before Symptom Onset.

Alzheimer's disease (AD), due to its multifactorial nature and complex etiology, poses challenges for research, diagnosis, and treatment, and impacts millions worldwide. To address the need for minimally invasive, repeatable measures that aid in AD diagnosis and progression monitoring, studies leveraging RNAs associated with extracellular vesicles (EVs) in human biofluids have revealed AD-associated changes. However, the validation of AD biomarkers has suffered from the collection of samples from differing points in the disease time course or a lack of confirmed AD diagnoses. Here, we integrate clinical diagnosis and postmortem pathology data to form more accurate experimental groups and use small RNA sequencing to show that EVs from plasma can serve as a potential source of RNAs that reflect disease-related changes. Importantly, we demonstrated that these changes are identifiable in the EVs of preclinical patients, years before symptom manifestation, and that machine learning models based on differentially expressed RNAs can help predict disease conversion or progression. This research offers critical insight into early disease biomarkers and underscores the significance of accounting for disease progression and pathology in human AD studies.

Long-Term Survival After Definitive Concurrent Chemoradiation Therapy for Synchronous Small Cell Neuroendocrine Carcinoma of the Urinary Bladder and Adenocarcinoma of the Prostate: A Case Report.

Available reports of synchronous prostate and bladder cancer have exclusively described radical cystoprostatectomy with or without perioperative chemotherapy as the treatment of choice. There are no reports of curative intent or definitive chemoradiation therapy for synchronous primary bladder and primary prostate cancers. Small cell carcinoma of the bladder is a rare and aggressive tumor. We present the first case of synchronous mixed small cell carcinoma and urothelial carcinoma of the urinary bladder and adenocarcinoma of the prostate in a 70-year-old male who attained long-term survival after curative intent and definitive concurrent chemoradiotherapy with minimal acute and late toxicities. The patient remained alive and disease-free at 41 months post-treatment and achieved excellent functional outcomes with organ preservation. Definitive chemoradiation therapy offers a safe and effective, curative-intent organ preservation treatment for localized synchronous prostate and bladder cancers.

Subclinical Upper Eyelid Ptosis in Asian Patients: The Role of Levator Advancement in Optimizing Outcomes in "Cosmetic" Upper Blepharoplasty.

BACKGROUND: Subclinical ptosis is prevalent in Asian patients presenting for aesthetic upper blepharoplasty. To achieve predictable and satisfactory results in these patients, addressing the ptosis component is critical. In this paper, we present a precision levator advancement technique that enabled us to predictably incorporate the levator advancement into our upper blepharoplasty to deliver more predictable results in these patients. MATERIALS AND METHODS: Asian patients with normal or near normal margin to reflex distance 1 (MRD 1 of ≥ 3.5 mm) and symptoms and signs of straining of the frontalis with eyelid opening were diagnosed with subclinical upper eyelid ptosis and included in this prospective study. The advancement required was estimated pre-operatively using a formula that we developed. Our surgical technique is presented in detail here, and our long-term results were analysed. RESULTS: From December 2019 to August 2022, 97 patients were included in this study. Sixty-five patients were primary cases and 32 were revision cases. The mean follow-up was 15 months. Of the 192 eyelids analysed, our formula was able to correctly identify the required fixation location in 69% of eyelids. In majority of the eyelids (94%), the correct location of fixation location within +/- 1 mm of the estimated location. All patients (100%) were satisfied with their long-term results. Our revision rate was 3%. CONCLUSIONS: Incorporating a precisely done levator advancement into the upper blepharoplasty in patients with subclinical ptosis is critical for optimizing the aesthetic and functional outcomes. This approach has enabled us to perform this procedure greater predictably in this group of patients. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Generation of two isogenic sickle cell disease induced pluripotent stem cell lines from testicular fibroblasts.

Curative bone marrow transplantation (BMT) therapies for sickle cell disease (SCD) can cause infertility. The Fertility Preservation Program (FPP) in Pittsburgh cryopreserves testicular tissues for SCD patients prior to BMT in anticipation that those tissues can be thawed in the future and matured to produce sperm. Here, we generated and validated two isogenic patient-derived induced pluripotent stem cell (iPSC) lines from testicular biopsy fibroblasts of a 12-year-old SCD patient.

Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

INTRODUCTION: The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. METHODS: At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. RESULTS: Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. CONCLUSION: The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

Upper Eyelid Ptosis Correction with Levator Advancement Using the Levator Musculoaponeurotic Junction Formula in Caucasian Patients.

INTRODUCTION: Upper eyelid ptosis correction is a challenging procedure. Here we report a novel approach to this procedure which we have found to be more accurate and predictable compared to conventional approaches. MATERIALS AND METHODS: A pre-operative system of assessment has been formulated to more accurately estimate the amount of levator advancement required. The levator advancement was referenced from a constant landmark - the musculoaponeurotic junction of the levator. The factors considered include 1) the amount of upper lid elevation required, 2) degree of compensatory brow elevation present 3) eye dominance. Our pre-operative assessment and surgical technique are presented in a series of detailed operative videos. The levator advancement is performed as planned pre-operatively with final adjustment made intraoperatively to achieve correct lid height and symmetry. RESULTS: Seventy-seven patients (154 eyelids) were prospectively analyzed in this study. We have found this approach to be reliable and accurate in predicting the required amount of levator advancement. Intraoperatively the formula correctly predicted the exact required fixation location in 63% of eyelids and to within +/ - 1 mm in 86% of cases. This may be used for patients with ptosis of varying severity, ranging from mild to severe eyelid ptosis. Our revision rate was 4. CONCLUSIONS: This approach is accurate in determining the fixation location needed for each individual. This has enabled levator advancement for ptosis correction to be performed with more precision and predictability.

Perspective on Schistosomiasis Drug Discovery: Highlights from a Schistosomiasis Drug Discovery Workshop at Wellcome Collection, London, September 2022.

In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and challenges associated with treating schistosomiasis. The aim of this meeting was to discuss the need for new treatments in view of the clinical situation and to ascertain what the key requirements would be for any potential new anti-schistosomals. This information will be essential to inform ongoing drug discovery efforts for schistosomiasis. We also discussed the potential drug discovery pathway and associated criteria for progressing compounds to the clinic. To date, praziquantel (PZQ) is the only drug available to treat all species causing schistosomiasis, but it is often unable to completely clear parasites from an infected patient, partially due to its inactivity against juvenile worms. PZQ-mediated mass drug administration campaigns conducted in endemic areas (e.g., sub-Saharan Africa, where schistosomiasis is primarily prevalent) have contributed to reducing the burden of disease but will not eliminate the disease as a public health problem. The potential for Schistosoma to develop resistance towards PZQ, as the sole treatment available, could become a concern. Consequently, new anthelmintic medications are urgently needed, and this Perspective aims to capture some of the learnings from our discussions on the key criteria for new treatments.

Midcheek Lift by Dissecting through the Facial Soft Tissue Spaces.

SUMMARY: The midcheek lift is one of the most effective procedures to rejuvenate the aging midface. However, it is a technically demanding procedure with the risk of complications, such as scleral show and ectropion. In 2015, the authors published their midcheek lift technique and outcomes. In this Video+ article, the authors present refinements and nuances of their surgical technique, emphasizing technical aspects of this procedure that have enabled them to perform the operation safely and effectively. The key concept of their approach is to minimize the trauma associated with surgical access, by dissection through the facial soft-tissue spaces that are the gliding planes of the midcheek. This minimizes postoperative bleeding and scarring, which are the main contributors to the dreaded postoperative contracture-related complications. To effectively mobilize the midcheek, precise sharp release of specific midcheek retaining ligaments separating these facial soft-tissue spaces is performed. Conservative skin excision is emphasized along with routine canthopexy for lower lid support.

Delayed prosthetic seroma: a localized inflammatory response to COVID vaccination and infection?

We present a patient whom we believe developed a late abdominal mesh collection in response to COVID-19 mRNA vaccination booster and COVID-19 infection. A polypropylene mesh was placed during her right breast reconstruction operation 2 years ago where she underwent a right transverse abdominis rectus muscle (TRAM) free flap. She recovered uneventfully from this operation. This lady, though vaccinated, developed respiratory symptoms and tested positive for COVID-19 infection 3 days after her booster injection. She then noticed right-sided abdominal swelling 3 days after the onset of respiratory symptoms. She only presented 1 month later due to a 7-day history of pain at the site of abdominal swelling. A computed tomography scan confirmed the presence of a seroma, and she underwent ultrasound-guided percutaneous drainage. A COVID Antigen Rapid Test of the fluid returned positive, though the PCR swab returned negative. There have been no published reports of periprosthetic mesh seroma after COVID-19 vaccination or infection to date. We wanted to share our experience so that other surgeons may be aware of this potential presentation given the current ongoing pandemic. Level of evidence: Level V, risk/prognostic.

No Increase in Acute or Late Radiation Toxicities in Patients With Ehlers-Danlos Syndrome Receiving Adjuvant Breast Radiation Therapy: A Report of Four Cases With Extended Follow-Up.

Ehlers-Danlos syndrome (EDS) consists of a heterogeneous group of congenital collagen formation disorders characterised by skin hyperextensibility, atrophic scarring, and generalized joint hypermobility. Collagen vascular disorders have been implicated in increased incidence and severity of radiation toxicities; however, there are limited reports on the safety of radiation therapy with EDS. We identified all patients with EDS who received adjuvant conventional and hypofractionated breast radiation therapy at our institution and reviewed patient, treatment, and toxicity characteristics. Four patients were identified with a median follow-up of 13.2 months. Acute toxicities were limited to grade 1 dermatitis in all four patients. No late toxicities were seen. In this report, radiation therapy to the breast with conventional and hypofractionated regimens resulted in no significant acute or late toxicity.

Improving Outcomes through Implementation of an Infant Spinal Anesthesia Program for Urologic Surgery Patients.

Introduction: Spinal anesthesia has a long history as an effective and safe technique to avoid general anesthesia in infants undergoing surgery. However, spinal anesthesia was rarely used as the primary anesthetic in this population at our institution. This healthcare improvement initiative aimed to increase the percentage of successful spinal placements as the primary anesthetic in infants undergoing circumcision, open orchidopexy, or hernia repair from 11% to 50% by December 31, 2019, and sustain that rate for 6 months. Methods: An interdisciplinary team created a key driver diagram and implemented the following interventions: education of nurses, surgeons, and patient families; focused anesthesiologist training on the infant spinal procedure; premedication; availability of supplies; and surgical schedule optimization. The team collected data retrospectively by reviewing electronic medical records (Cerner, North Kansas City, Mo.). The primary outcome was the percentage of infants undergoing circumcision, open orchidopexy, or hernia repair who received a successful spinal as the primary anesthetic. The team tracked this measure and evaluated using a statistical process control chart. Results: Between August 1, 2018, and February 29, 2020, researchers identified 470 infants (235 preintervention and 235 postintervention) who underwent circumcision, open orchidopexy, or inguinal hernia repair. Following the interventions in this project, there was a statistically significant increase in successful spinal placement from 11% to 45% (P < 0.0001). Conclusion: This quality improvement project successfully increased the percentage of patients receiving spinal anesthesia for specific surgical procedures by increasing the number of patients who underwent successful spinal anesthesia placement.

Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress.

Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death.