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Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7-12 nmol/l). This was a multicentre United Kingdom study conducted in secondary care hospital outpatients. Male survivors of testicular cancer, lymphoma, and leukaemia aged 25-50 years with morning total serum testosterone 7-12 nmol/l were recruited. A total of 136 men were randomised between July 2012 and February 2015 (42.6% aged 25-37 years, 57.4% 38-50 years, 88% testicular cancer, 10% lymphoma, matched for body mass index [BMI]). Participants were randomised 1:1 to receive testosterone (Tostran 2% gel) or placebo for 26 weeks. A dose titration was performed after 2 weeks. The coprimary end points were trunk fat mass and SF36 Physical Functioning score (SF36-PF) at 26 weeks by intention to treat. At 26 weeks, testosterone treatment compared with placebo was associated with decreased trunk fat mass (-0.9 kg, 95% CI -1.6 to -0.3, p = 0.0073), decreased whole-body fat mass (-1.8 kg, 95% CI -2.9 to -0.7, p = 0.0016), and increased lean body mass (1.5 kg, 95% CI 0.9-2.1, p < 0.001). Decrease in fat mass was greatest in those with a high truncal fat mass at baseline. There was no treatment effect on SF36-PF or any other QoL scores. Testosterone treatment was well tolerated. The limitations of our study were as follows: a relatively short duration of treatment, only three cancer groups included, and no hard end point data such as cardiovascular events. In young male cancer survivors with low-normal morning total serum testosterone, replacement with testosterone is associated with an improvement in body composition. ISRCTN: 70274195, EudraCT: 2011-000677-31.

PurposeBack pain is a major problem worldwide and is linked to intervertebral disc degeneration and Modic change. Several studies report growth of bacteria following extraction of degenerate discs at spine surgery. A pathophysiological role for infection in back pain has been proposed.MethodWe conducted a PRISMA systematic review. MEDLINE, PubMed, Scopus and Web of Science were searched with the terms Modic change, intervertebral dis*, bacteria, microb*, and infect*. Date limits of 2001–2021 were set. Human studies investigating the role of bacteria in disc degeneration or Modic change in vertebrae were included.ResultsThirty-six articles from 34 research investigations relating to bacteria in human degenerate discs were found. Cutibacterium acnes was identified in pathological disc material. A ‘candidate bacterium’ approach has been repeatedly adopted which may have biased results to find species a priori, with disc microbial evidence heavily weighted to find C. acnes.ConclusionEvidence to date implicates C. acnes identified through culture, microscopy and sequencing, with some suggestion of diverse bacterial colonisation in the disc. This review found studies which used culture methods and conventional PCR for bacterial detection.Further agnostic investigation using newer methods should be undertaken.

IntroductionLow back pain is the leading contributor to disability burden globally. It is commonly due to degeneration of the lumbar intervertebral discs (LDD). Magnetic resonance imaging (MRI) is the current best tool to visualize and diagnose LDD, but places high time demands on clinical radiologists. Automated reading of spine MRIs could improve speed, accuracy, reliability and cost effectiveness in radiology departments. The aim of this review and meta-analysis was to determine if current machine learning algorithms perform well identifying disc degeneration, herniation, bulge and Modic change compared to radiologists.MethodsA PRISMA systematic review protocol was developed and four electronic databases and reference lists were searched. Strict inclusion and exclusion criteria were defined. A PROBAST risk of bias and applicability analysis was performed.Results1350 articles were extracted. Duplicates were removed and title and abstract searching identified original research articles that used machine learning (ML) algorithms to identify disc degeneration, herniation, bulge and Modic change from MRIs. 27 studies were included in the review; 25 and 14 studies were included multi-variate and bivariate meta-analysis, respectively. Studies used machine learning algorithms to assess LDD, disc herniation, bulge and Modic change. Models using deep learning, support vector machine, k-nearest neighbors, random forest and naïve Bayes algorithms were included. Meta-analyses found no differences in algorithm or classification performance. When algorithms were tested in replication or external validation studies, they did not perform as well as when assessed in developmental studies. Data augmentation improved algorithm performance when compared to models used with smaller datasets, there were no performance differences between augmented data and large datasets.DiscussionThis review highlights several shortcomings of current approaches, including few validation attempts or use of large sample sizes. To the best of the authors' knowledge, this is the first systematic review to explore this topic. We suggest the utilization of deep learning coupled with semi- or unsupervised learning approaches. Use of all information contained in MRI data will improve accuracy. Clear and complete reporting of study design, statistics and results will improve the reliability and quality of published literature.

Hybrid breast reconstruction (HBR) combines autologous tissue and bio-prosthetic breast reconstruction techniques. This method addresses many challenges associated with stand-alone techniques, including inadequate volume with autologous reconstruction and esthetic issues like rippling in implant-based reconstruction. However, despite its promising advantages, HBR remains underutilized. This review explores the development of HBR, surgical techniques, clinical outcomes, current barriers to adoption, and the future potential of this innovative approach to breast reconstructive surgery.

Background and Objectives: Pediatric patients can acquire scars from both accidental injury and surgical procedures. While scars cannot be avoided if a full-thickness injury occurs, scar visibility may be minimized through a variety of approaches. In this narrative review, we evaluate the current evidence and propose an algorithm for scar management in pediatric patients. Materials and Methods: A review of the literature was performed for scar management techniques for pediatric patients. Management modalities based on the type of scar and dosing, treatment regimen, and safety profiles are described in this article and used to create a scar management algorithm. Results: The initial step to scar management in the pediatric population involves ensuring minimal wound tension, which can be achieved through making the incision along relaxed skin tension lines, and early, minimal tension wound closure. Subsequent treatments to optimize scar care should begin 2–3 weeks following wound closure and involve the application of silicone gel or sheets and scar massaging. When topical products are insufficient, laser therapy can be utilized for the management of immature erythematous or thick scars. When mature, pathological scars form such as atrophic scars, hyperpigmentation, hypertrophic scars, or keloids, a combination of modalities is recommended. These modalities vary by scar type and include retinoids and dermabrasion for atrophic scars; retinoids, hydroquinone, and laser therapy for hyperpigmentation; and pressure therapy, corticosteroids, and laser therapy for hypertrophic scars and keloids. When mature, pathological scars persist following 12 months of non-invasive therapies, surgical excision should be considered. Conclusions: Several treatment options are available to manage scars in the pediatric population depending on scar type.

ObjectiveThe chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample.DesignCross-sectional study.SettingCommunity-dwelling cohort.ParticipantsTwins from the TwinsUK cohortPrimary and secondary outcome measuresWe compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing.ResultsIn N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance.ConclusionOur findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS.

Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two ( p  < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure ( p  < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19–2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14–2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.

Breast cancers are most frequently oestrogen receptor (ER) and progesterone receptor (PR) positive and [18F]Fluorodeoxyglucose PET-CT (FDG) has lower sensitivity for these subtypes. The gastrin-releasing peptide receptor (GRPR) is overexpressed in ER+/PR+ breast cancers. This study assessed the safety and potential of [64Cu]Cu-Sarcophagine (SAR)-Bombesin PET/CT (BBN) in re-staging metastatic ER+/PR+/human epidermal growth-factor-2-negative (HER2-) breast cancer. Seven patients with metastatic ER+/PR+/HER2- breast cancer undergoing staging underwent [64Cu]Cu-SAR-BBN PET-CT. Bloods, vital signs and electrocardiogram, blood tracer-clearance and dosimetry were undertaken. GRPR status was assessed in available metastatic biopsy samples. Staging with conventional imaging ([18F]FDG, bone scan and diagnostic CT) was within 3 weeks of [64Cu]Cu-SAR-BBN PET/CT. PET scans were assessed visually and quantitatively. Seven patients underwent imaging. One of the seven had de-novo metastatic breast cancer and six of the seven recurrent metastatic disease. Two of the seven had lobular subtype. No adverse events were reported. All seven patients were positive on conventional imaging (six of seven on FDG). [64Cu]Cu-SAR-BBN imaging was positive in five of the seven. Both [64Cu]Cu-SAR-BBN-negative patients had disease identified on [18F]FDG. One patient was [64Cu]Cu-SAR-BBN positive/[18F]FDG negative. Four of seven patients were [64Cu]Cu-SAR-BBN positive/[18F]FDG positive. In these four, mean SUVmax was higher for [64Cu]Cu-SAR-BBN than [18F]FDG (SUVmax 15 vs. 12). In the classical lobular subtype (two of seven), [64Cu]Cu-SAR-BBN was more avid compared to [18F]FDG (SUVmax 20 vs. 11, and 20 vs. <3). Dosimetry calculations estimated whole-body effective dose for 200 MBq of [64Cu]Cu-SAR-BBN to be 1.9 mSv. [64Cu]Cu-SAR-BBN PET/CT appears safe and may have diagnostic value in metastatic ER+/PR+/HER2- breast cancer, particularly the lobular subtype. Further evaluation is warranted.