Vertebral Metastasis as the Initial Manifestation of Colon Cancer

Oncology guidelines currently recommend against performing colonoscopies in the workup of adenocarcinoma of unknown primary unless colonic malignancy is otherwise suggested by clinical signs or symptoms. We present 2 cases of metastatic colonic adenocarcinoma that presented only with neurologic symptoms from vertebral metastasis. Although bony metastases are a rare presentation of colon cancer and colonoscopy is not warranted in the initial workup of adenocarcinoma of unknown primary, we describe these cases as a reminder that bony metastases do not rule out a colon cancer diagnosis

Characterizing the Features of Mitotic Figures Using a Conditional Diffusion Probabilistic Model

Mitotic figure detection in histology images is a hard-to-define, yet clinically significant task, where labels are generated with pathologist interpretations and where there is no ``gold-standard'' independent ground-truth. However, it is well-established that these interpretation based labels are often unreliable, in part, due to differences in expertise levels and human subjectivity. In this paper, our goal is to shed light on the inherent uncertainty of mitosis labels and characterize the mitotic figure classification task in a human interpretable manner. We train a probabilistic diffusion model to synthesize patches of cell nuclei for a given mitosis label condition. Using this model, we can then generate a sequence of synthetic images that correspond to the same nucleus transitioning into the mitotic state. This allows us to identify different image features associated with mitosis, such as cytoplasm granularity, nuclear density, nuclear irregularity and high contrast between the nucleus and the cell body. Our approach offers a new tool for pathologists to interpret and communicate the features driving the decision to recognize a mitotic figure.Comment: Accepted for Deep Generative Models Workshop at Medical Image Computing and Computer Assisted Intervention (MICCAI) 202

Inhibition of stromal cell-derived factor-1α further impairs diabetic wound healing

ObjectiveImpaired diabetic wound healing is associated with abnormal stromal cell-derived factor (SDF)-1α production, decreased angiogenesis, and chronic inflammation. Lentiviral-mediated overexpression of SDF-1α can correct the impairments in angiogenesis and healing in diabetic wounds. We hypothesized that SDF-1α is a critical component of the normal wound-healing response and that inhibition of SDF-1α would further delay the wound-healing process.MethodsdB/Db diabetic mice and Db/+ nondiabetic mice were wounded with an 8-mm punch biopsy and the wounds treated with a lentiviral vector containing either the green fluorescent protein (GFP) or SDF-1α inhibitor transgene. The inhibitor transgene is a mutant form of SDF-1α that binds, but does not activate, the CXCR4 receptor. Computerized planimetry was used to measure wound size daily. Wounds were analyzed at 3 and 7 days by histology and for production of inflammatory markers using real-time polymerase chain reaction. The effect of the SDF-1α inhibitor on cellular migration was also assessed.ResultsInhibition of SDF-1α resulted in a significant decrease in the rate of diabetic wound healing, (3.8 vs 6.5 cm2/day in GFP-treated wounds; P = .04), and also impaired the early phase of nondiabetic wound healing. SDF-1α inhibition resulted in fewer small-caliber vessels, less granulation tissue formation, and increased proinflammatory gene expression of interleukin-6 and macrophage inflammatory protein-2 in the diabetic wounds.ConclusionsThe relative level of SDF-1α in the wound plays a key role in the wound-healing response. Alterations in the wound level of SDF-1α, as seen in diabetes or by SDF-1α inhibition, impair healing by decreasing cellular migration and angiogenesis, leading to increased production of inflammatory cytokines and inflammation. Inhibition of SDF-1α further impairs diabetic wound healing.Clinical RelevanceDiabetes results in a significant impairment in wound healing, leading to significant morbidity and health care expenditures. The pathophysiology that underlies this process is multifactorial, including abnormal growth factor production, cellular migration, and cellular function. Stromal cell-derived factor (SDF)-1α is a key chemokine involved in the wound-healing process and is involved in cellular recruitment and angiogenesis. SDF-1α is decreased in diabetic individuals. This study showed that inhibition of SDF-1α results in an even more dramatic delay in the diabetic wound-healing process and even results in a delay in the early phases of wound healing in normal mice, further supporting its role in wound healing. Inhibition of this chemokine promotes greater inflammatory cytokine production, inflammatory cell migration, and less vasculogenesis after dermal wounding. This study identifies SDF-1α as an essential component of normal wound healing and provides a potential therapeutic target to improve the diabetic wound-healing impairment

Percutaneous vertebral compression fracture management with polyethylene mesh-contained morcelized allograft bone

Study design    A comprehensive systematic review of the literature. Objectives To assess the modern literature on the use of polyethylene mesh-contained morcelized allograft (PMCMA) bone for spinal fusion and vertebral compression fracture management. Summary of background data    There are presently no systematic reviews of PMCMA. Methods    A systematic literature review was performed within three databases (OVID, PubMed, and Google Scholar) using the following keyword search terms: vertebroplasty, kyphoplasty, vertebral compression fracture, percutaneous, polyethylene mesh, and osteoporosis. Results    The initial search identified 764 items, from which two pertinent technique-based articles were identified. There were no published scientific peer-reviewed or case series reporting the clinical results of this technique. The use of PMCMA in the management of vertebral compression fractures (VCFs) is similar to vertebroplasty and kyphoplasty. This novel, percutaneous system uses the properties of granular mechanics to establish a conforming, semirigid graft that is purportedly capable of withstanding physiologic loads. Discussion    PMCMA is a novel percutaneous technology for the management of VCF and possibly for use as a conforming interbody graft. The available published literature lacks outcome data of the use of PMCMA. Careful, independent research is needed to assess the viability of this technology and its long-term results

A novel PEG–haloperidol conjugate with a non-degradable linker shows the feasibility of using polymer–drug conjugates in a non-prodrug fashion

A PEG–haloperidol conjugate containing a non-biodegradable linker was synthesised. Incubation with rat plasma demonstrated excellent linker stability, and competition radioligand binding assays demonstrated retained binding to the D2-receptor. In silico studies predicted that the conjugate will not cross the blood–brain barrier (BBB), thus potentially restricting haloperidol action to one side of the BBB

Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis.

BACKGROUND: Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. METHODS: We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. FINDINGS: We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8-6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500-340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600-282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600-193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400-234 300), with 135 900 (75%; [95% CI 93 900-163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10-19). INTERPRETATION: Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. FUNDING: None

Perineum: Surface anatomy & skin incisions

MP4. .File size is approximately 14 M

Neck: Anterior neck- external carotid artery & branches

MP4;no audio component. File size is approximately 7 MB

Upper Limb: Brachial plexus - roots & associated branches

MP4; no audio component. File size is approximately 3 M

Upper Limb: Dorsum of hand - radial artery & branches

MP4; no audio component. File size is approximately 7 MB