COVID-19 Vaccination Safety Profiles in Patients With Solid Tumour Cancers: A Systematic Review.

Vaccination has become an essential means of protection for solid tumour patients against coronavirus disease 2019 (COVID-19). In this systematic review, we sought to identify common safety profiles of the COVID-19 vaccine in patients with solid tumours. A search of Web of Science, PubMed, EMBASE and Cochrane was conducted for studies in English full-text that reported side-effect data experienced by patients with cancer who were at least 12 years old with solid tumours or a recent history of solid tumours after receiving either one or multiple doses of the COVID-19 vaccination. Study quality was assessed with the Newcastle Ottawa Scale criteria. Acceptable study types were retrospective and prospective cohorts, retrospective and prospective observational studies, observational analyses and case series; systematic reviews, meta-analyses and case reports were excluded. Among local/injection site symptoms, the most commonly reported were injection site pain and ipsilateral axillary/clavicular lymphadenopathy, whereas the most commonly reported systemic effects were fatigue/malaise, musculoskeletal symptoms and headache. Most side-effects reported were characterised as mild to moderate. A thorough evaluation of the randomised controlled trials for each featured vaccine led to the conclusion that in the USA and abroad, the safety profile seen in patients with solid tumours is comparable with that seen in the general public.

Rapid On-Site Microscopy and Mapping of Diagnostic Biopsies for See-And-Treat Guidance of Localized Prostate Cancer Therapy.

Prostate cancer continues to be the most diagnosed non-skin malignancy in men. While up to one in eight men will be diagnosed in their lifetimes, most diagnoses are not fatal. Better lesion location accuracy combined with emerging localized treatment methods are increasingly being utilized as a treatment option to preserve healthy function in eligible patients. In locating lesions which are generally <2cc within a prostate (average size 45cc), small variance in MRI-determined boundaries, tumoral heterogeneity, patient characteristics including location of lesion and prostatic calcifications, and patient motion during the procedure can inhibit accurate sampling for diagnosis. The locations of biopsies are recorded and are then fully processed by histology and diagnosed via pathology, often days to weeks later. Utilization of real-time feedback could improve accuracy, potentially prevent repeat procedures, and allow patients to undergo treatment of clinically localized disease at earlier stages. Unfortunately, there is currently no reliable real-time feedback process for confirming diagnosis of biopsy samples. We examined the feasibility of implementing structured illumination microscopy (SIM) as a method for on-site diagnostic biopsy imaging to potentially combine the diagnostic and treatment appointments for prostate cancer patients, or to confirm tumoral margins for localized ablation procedures. We imaged biopsies from 39 patients undergoing image-guided diagnostic biopsy using a customized SIM system and a dual-color fluorescent hematoxylin & eosin (H&E) analog. The biopsy images had an average size of 342 megapixels (minimum 78.1, maximum 842) and an average imaging duration of 145 s (minimum 56, maximum 322). Comparison of urologist's suspicion of malignancy based on MRI, to pathologist diagnosis of biopsy images obtained in real time, reveals that real-time biopsy imaging could significantly improve confirmation of malignancy or tumoral margins over medical imaging alone.

Advanced papillary renal cell carcinoma: Epidemiology, genomic drivers, current therapies, and ongoing trials.

Papillary renal cell carcinoma (PRCC) is the most common subtype of non-clear cell renal cell carcinoma. PRCC can be subdivided into types 1 and 2 based on histology, each associated with different genetic mutations. The MET gene is commonly altered in type 1 PRCC while multiple alterations are involved in type 2 PRCC. PRCC is an aggressive cancer with a predominance in male and black patients and poor prognosis. Due to its rarity, there was a lack of convincing prospective data to guide treatment; hence, therapies were previously extrapolated from clear cell renal cell carcinoma with mixed results. More recently, some phase 2 trials focused on PRCC have been promising. Tyrosine kinase inhibitor (TKI) monotherapy is considered the standard of care, and combination strategies with TKIs and immune checkpoint inhibitors are emerging. Genetic profiling and large-scale clinical trials are needed to inform targeted treatment of PRCC.

Oral 11ß-HSD1 inhibitor AZD4017 improves wound healing and skin integrity in adults with type 2 diabetes mellitus: a pilot randomized controlled trial.

BACKGROUND: Chronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11ß-hydroxysteroid dehydrogenase type 1, 11ß-HSD1) impair wound healing. OBJECTIVES: Efficacy, safety, and feasibility of 11ß-HSD1 inhibition for skin function and wound healing. DESIGN: Investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial. METHODS: Single-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11ß-HSD1 inhibitor AZD4017 (n = 14) or placebo (n = 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized. RESULTS: Exploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h ex vivoskin 11ß-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: -3.4 to 5.5) but reduced systemic 11ß-HSD1 activity by 87% (69-104%). Wound diameter was 34% (7-63%) smaller with AZD4017 at day 2, and 48% (12-85%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9/month, 27/28, and 95.3%, respectively. CONCLUSION: A phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers. SIGNIFICANCE STATEMENT: Stress hormone activation by the enzyme 11ß-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11ß-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11ß-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11ß-HSD type 1 as a novel therapeutic target forchronic wounds.

A Neonate Born with Holoprosencephaly Sequence of A Gestational Diabetic Mother: A Rare Case.

Holoprosencephaly is a rare spectrum of congenital malformation associated with midline facial defects and absence of olfactory tract. Sequence occurs at 4th to 8th week of gestational age due to failure or incomplete diverticulation and cleavage of primitive prosencephalon. It is most common brain malformation with an incidence 1:250 in conceptuses and associated with a high rate of spontaneous abortion, and prevalence of 1:16000 in live borns. The etiopathogenesis of holoprosencephaly is heterogeneous and multifactorial, may be environmental, metabolic factors or teratogenic including insulin-dependent maternal diabetes, alcohol consumption. In this study, we described a case of holoprosencephaly neonate with 34 weeks gestational age and antenatal ultrasonography diagnosed as congenital defects in the central nervous system, asymmetric growth of head. After birth the infant was presented with multiple congenital anomalies (cleft lip, cleft palate, microphthalmia, absent philtrum, absent nasal septum with single naris) similar to holoprosencephaly sequence.

Identification of translational dermatology research priorities in the U.K.: results of an electronic Delphi exercise.

BACKGROUND: Translational research is the direct application of basic and applied research to patient care. It is estimated that there are at least 2000 different skin diseases; thus, there are considerable challenges in seeking to undertake research on each of these disorders. OBJECTIVES: This electronic Delphi (e-Delphi) exercise was conducted in order to generate a list of translational dermatology research questions that are regarded as a priority for further investigations. METHODS: During the first phase of the e-Delphi exercise, 228 research questions were generated by an expert panel that included clinical academic dermatologists, clinical dermatologists, nonclinical scientists, dermatology trainees and representatives from patient support groups. RESULTS: Following completion of the second and third phases, 40 questions on inflammatory skin disease, 20 questions on structural skin disorders/genodermatoses, 37 questions on skin cancer and eight miscellaneous questions were designated as priority translational dermatology research questions (PRQs). In addition to PRQs on a variety of disease areas (including multiple PRQs on psoriasis, eczema, squamous cell carcinoma and melanoma), there were a number of cross-cutting themes that identified a need to investigate mechanisms/pathogenesis of disease and the necessity to improve treatments for patients with skin disease. CONCLUSIONS: It is predicted that this list of PRQs will help to provide a strategic direction for translational dermatology research in the U.K. and that addressing this list of questions will ultimately provide clinical benefit for substantial numbers of patients with skin disorders.

An uncommonly encountered perirenal mass: Robotic resection of renal vein leiomyosarcoma.

Primary leiomyosarcoma (LMS) of the renal vein is a rare tumour and poorly described in the literature. Surgical resection, using open and laparoscopic approaches, is the mainstay of treatment. In this report, we describe a patient with left renal vein LMS, report the first robotic laparoscopic resection for this tumor, and review the typical presentation, imaging, pathology and treatment for this rare clinical entity.

Dynamics of reactive chromatographic columns of inert core/hollow/film coated spherical packing: an analytical solution and applications.

The transient behavior of reactive-diffusive fixed-bed (chromatographic columns or reactors) packed with inert core/shell core/hollow/thin film coated monodisperse spherical rigid particles is investigated. We modeled the reactive sorption system with linear mass exchange law between the flowing and the stationary phases. The coupled governing partial differential equations were integrated analytically using Laplace transformations. The analytical closed form solution involves two infinite integrals. The closed form solution was integrated numerically and the breakthrough curves of the system were studied under the influence of the system parameters. The limiting cases are discussed, a simple asymptotic closed form solution for fixed-bed desorbers with monodisperse spherical particles is obtained, and results are generalized for similar kinetics of reactive chromatographic columns (fixed-beds) for diffusion/absorption into the inert core spherical packing. Further, potential applications of the mathematical model and results in processes such as liquid vapor extraction, various forms of chromatography, reactive sorption, multifunctional reactors, process intensification, and regeneration of ion exchange columns are briefly discussed.

Lacrimal gland sparing IgG4-related disease in the orbit.

PURPOSE: We report an unusual case of orbital IgG4-related disease and discuss the distinguishing characteristics of the ophthalmic disease subtype. DESIGN: Case report. METHODS: Literature review and case description. RESULTS: Although lacrimal gland involvement has always been reported and elevated serum IgG4 is commonly observed, our case demonstrated neither in light of biopsy-proven IgG4 orbital involvement. A course of systemic steroids resolved our patient's periorbital abnormalities. CONCLUSIONS: IgG4-related orbital disease mandates a high index of suspicion, and should be confirmed by tissue biopsy. Possible progression to MALT lymphoma necessitates close surveillance and may require repeat biopsy.

Updates from the Sixth International Congress 'Psoriasis: from Gene to Clinic', the Queen Elizabeth II Conference Centre, London, U.K., 1-3 December 2011.

The 15 years between the First International Congress 'Psoriasis: from Gene to Clinic' and the Sixth Congress held in London from 1 to 3 December 2011 have seen extraordinary progress in the sciences that are relevant to psoriasis and therapeutics that have transformed its treatment. Over this time, 'Psoriasis: from Gene to Clinic' has emerged as the premier conference for clinicians and scientists interested in this field. Its popularity is attested to by the 450 registered delegates from the U.K. and around the world, which necessitated a change of venue to the excellent facilities of the Queen Elizabeth II Conference Centre. Although the content has evolved over the years, the structure of this 3-day conference has remained similar. The first day was given to genetics, comorbidities and outcome measures. Immunology and immunity were covered on the second day and therapeutics on the third. The stature of the three keynote lecturers and eight invited speakers was truly world class and their presentations were interspersed with 23 free communications. Here we review highly selected personal highlights of the meeting that we hope will be of general interest.

Prevalence and risk factors of erectile dysfunction among patients attending primary health care centres in Qatar.

Erectile dysfunction is a common health problem affecting the quality of life of men of all ages. The aim of this study was to find the prevalence of and significant risk factors for erectile dysfunction among men of all nationalities attending primary health care centres in Qatar for any reason. Respondents aged > 30 years (n = 1139) completed the sexual health inventory for men plus a questionnaire about their demographic characteristics, lifestyle habits and presence of chronic diseases. The total prevalence of erectile dysfunction was 56.9% (32.7% mild and 2.3% severe cases). All studied sociodemographic variables showed a significant association with erectile dysfunction. A lower prevalence of erectile dysfunction was found in smokers and those who exercised. More than 1 sexual partner, obesity and having a chronic disease (hypertension, coronary heart disease, hypercholesterolaemia or diabetes mellitus) were significantly positively associated with erectile dysfunction.

What's new in atopic eczema? An analysis of systematic reviews published in 2009-2010.

This review provides a summary of key findings from 18 systematic reviews on atopic eczema, published or indexed between January 2009 and 24 August 2010. There was no good evidence on the possible benefit of organic food consumption and eczema. Maternal intake of fish or fish oil may be associated with a reduced risk of eczema in offspring, although further studies are needed. There is some evidence that partially hydrolysed infant formulas rather than standard formulas may be associated with a reduced risk of eczema in infants, but there are shortcomings in the existing evidence. An inverse relationship has been found between gliomas/acute lymphoblastic leukaemia and allergic disease/eczema, but there appears to be no association between multiple sclerosis and eczema. Attention deficit hyperactivity disorder does appear to be associated with eczema, but there is no evidence of a causal link. The risk of eczema seems to be increased in urban compared with rural areas. Some new evidence has suggested superiority of 1% pimecrolimus over potent and mild corticosteroids at 6 months but not 12 months, and there is some evidence for superiority of 0.03% and 0.1% tacrolimus over 1% pimecrolimus. An updated Cochrane Review still found no evidence of a benefit from any form of antistaphylococcal treatment in managing clinically infected or uninfected eczema. The evidence base is poor for bath emollients, occlusive treatments (e.g., wet and dry wraps) and woven silk clothing in treating eczema. In general, the methods used in most systematic reviews of eczema need to be reported more clearly, especially with regard to a more vigorous quality assessment of included studies. Included studies are frequently heterogeneous, proxy reporting is common, and appropriate disease definitions are often lacking. Better adherence to existing guidance on trial reporting and prospective registration of clinical trials may help improve the quality of studies.

Prevalence and risk factors of erectile dysfunction among patients attending primary health care centres in Qatar

Erectile dysfunction is a common health problem affecting the quality of life of men of all ages. The aim of this study was to find the prevalence of and significant risk factors for erectile dysfunction among men of all nationalities attending primary health care centres in Qatar for any reason. Respondents aged > 30 years [N = 1139] completed the sexual health inventory for men plus a questionnaire about their demographic characteristics, lifestyle habits and presence of chronic diseases. The total prevalence of erectile dysfunction was 56.9% [32.7% mild and 2.3% severe cases]. All studied sociodemographic variables showed a significant association with erectile dysfunction. A lower prevalence of erectile dysfunction was found in smokers and those who exercised. More than 1 sexual partner, obesity and having a chronic disease [hypertension, coronary heart disease, hypercholesterolaemia or diabetes mellitus] were significantly positively associated with erectile dysfunction

Permeability and percolation of anisotropic three-dimensional fracture networks.

The percolation properties and permeability of a group of anisotropic three-dimensional fracture networks are studied numerically. Finite-size scaling is used to extrapolate the percolation thresholds of infinite networks in three spatial directions, i.e., X , Y , and Z directions. The influence of the angular dispersion parameter of fracture orientations on percolation thresholds is analyzed. In this analysis, we considered a family of fractures in a three-dimensional space that are oriented around the Z axis based on the Fisher distribution. We revealed that increased anisotropy leads to decreased percolation thresholds in both X and Y directions, and in these two directions percolation thresholds in anisotropic networks demonstrate a declining trend as anisotropy goes up. However, in the Z direction the trend is the opposite. The fracture networks are triangulated via an advancing front technique and the macroscopic permeability of the networks is determined by solving the two-dimensional Darcy equation in each fracture. We found that the macroscopic permeability in the X and Y directions is higher than the associated permeability of isotropic fracture networks, and this property for anisotropic networks in the Z direction is lower compared with that of the isotropic case. Furthermore, as the anisotropy of networks increases the differences become more remarkable.