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Procedural dermatology includes invasive conventional dermatologic surgeries which involve significant use of knife and suture, minimally invasive procedures and device-based procedures. Device-based procedures are the easiest to learn and are less prone to human errors due to automation but can lead to monotony, while conventional surgeries require significant skill, craftsmanship and interest. There has been a recent shift in the approach to procedural dermatology as a therapeutic option with complementary and combination models replacing the conventional hierarchical model in which procedures were last in the step-ladder approach. The demand for both conventional dermatologic surgeries and minimally invasive cosmetic procedures is increasing. Unfortunately, this demand has not been met with adequate supply. Consequently, the number of trained professionals with expertise in these procedures is very limited; they are far outnumbered by unqualified practitioners. A limited number of dermatologic surgeons practicing conventional surgeries has resulted in huge waiting lists for vitiligo surgeries, inappropriate excisions for skin cancers and poor cosmetic outcomes of excisions without proper knowledge of flaps and grafts. Increasingly procedures are being performed by inadequately trained personnel, resulting in complications. There is also an absence of good quality research on the subject of procedural dermatology, which has resulted in a lack of standardisation of various procedures and knowledge about the efficacy of various drug-procedure and procedure-procedure combinations. An increasing variety of gimmicky but costly procedures are being offered to the public without much evidence of efficacy. Individual institutional and broad policy directives are needed to address these issues. Special emphasis is required on formal hands-on procedural dermatology training during residency and beyond it.

Various overlapping risk factors lead to coronary artery disease (CAD). The atherogenic index of plasma (AIP) is a marker for CAD severity and progression. However, little is known about its contribution to the residual risk of CAD observed in the absence of all typical risk factors.A prospective cohort study of 366 Indian patients undergoing coronary computed tomography (CT) angiography and diagnosed with stable CAD. Diabetes, hypertension, hypercholesterolemia, smoking, previous CAD, alcohol or lipid-lowering medication intake, renal, liver or thyroid dysfunction were exclusion criteria. Coronary stenosis was graded using the CAD-reporting and data system (CAD-RADS™) system. Lipid profile, HbA1c, uric acid, highly sensitive C-reactive protein (hsCRP) and anthropometric measurements were taken. AIP, triglyceride/high-density lipoprotein cholesterol (HDLc) and total cholesterol (Tc)/HDLc ratios were calculated. Independent predictors of CAD severity and the occurrence of major adverse cardiac events (MACE) during 2.57 (0.52) years of follow-up were identified using logistic regression and Cox proportional hazards regression.Sixty patients experienced a MACE during a cumulative 887.03 person-years. HbA1c, uric acid, hsCRP, Tc/HDLc and AIP were independent predictors of severe coronary lesions (CAD-RADS 4,5) on multivariate analysis with odds ratio 4.52 (2.37-8.61), 1.41 (1.08-1.84), 1.33 (1.09-1.62), 1.76 (1.27-2.44) and 1.29 (1.11-1.50), respectively. Only AIP and Tc/HDLc were independent predictors of MACE with hazard ratios of 1.41 (1.20-1.65) and 1.78 (1.33-2.39) besides patient age and CAD severity.AIP is associated with both the severity of CAD and the occurrence of MACE within 3 years. It could serve as an effective marker of residual risk of CAD in patients devoid of traditional risk factors. Lipid-profile ratios, such as AIP are cost-effective and accessible parameters suitable for low and middle-income settings.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.

Complete Supplementary Information for the manuscript, including Supplemental Figures 1-16 and tables 1-4.

Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due to a lack of methods to measure and localize protease activity directly within the tissue microenvironment, the design of protease-activated agents has been necessarily empirical, yielding suboptimal results when translated to patients. To address the need for spatially resolved protease activity profiling in cancer, we developed a new class of in situ probes that can be applied to fresh-frozen tissue sections in a manner analogous to immunofluorescence staining. These activatable zymography probes (AZP) detected dysregulated protease activity in human prostate cancer biopsy samples, enabling disease classification. AZPs were leveraged within a generalizable framework to design conditional cancer diagnostics and therapeutics and showcased in the Hi-Myc mouse model of prostate cancer, which models features of early pathogenesis. Multiplexed screening against barcoded substrates yielded a peptide, S16, that was robustly and specifically cleaved by tumor-associated metalloproteinases in the Hi-Myc model. In situ labeling with an AZP incorporating S16 revealed a potential role of metalloproteinase dysregulation in proliferative, premalignant Hi-Myc prostatic glands. Systemic administration of an in vivo imaging probe incorporating S16 perfectly classified diseased and healthy prostates, supporting the relevance of ex vivo activity assays to in vivo translation. We envision AZPs will enable new insights into the biology of protease dysregulation in cancer and accelerate the development of conditional diagnostics and therapeutics for multiple cancer types.Significance:Visualization of protease activity within the native tissue context using AZPs provides new biological insights into protease dysregulation in cancer and guides the design of conditional diagnostics and therapeutics.

Context: Accurate diagnosis may be challenging in nonneoplastic lung diseases. Newer techniques such as bronchoalveolar lavage (BAL), bronchial brushing (BB), and transbronchial needle aspiration (TBNA) have been studied mainly in lung cancers. Aim: This study assesses the efficacy of BAL, BB, and TBNA in non-neoplastic lung diseases, against a gold standard of transbronchial lung biopsy (TBLB). Settings and Design: Three-year prospective study in a tertiary care center in North India. Methodology: Adult patients (n = 137) with nonimproving respiratory complaints and clinical and radiological suspicion of having a pulmonary pathology were recruited. Patients of malignancy were excluded. Patients for whom all four samples of BAL, BB, TBNA, and TBLB were unavailable were excluded. Statistical Analysis Used: Sensitivity (SN), specificity (SP), positive predictive value, and negative predictive value for all tests were computed and represented with 95% confidence intervals. TBLB was taken to be the gold standard. Two or more tests taken in combination were also analyzed. Results: We studied the patients of tuberculosis, interstitial pneumonia, acute and chronic nonspecific inflammation, sarcoidosis, fungal infection, interstitial lung disease, eosinophilic pneumonitis, and pulmonary alveolar proteinosis in this study. TBNA had higher SN and SP (59.8% and 96.7%) than BB (57.0% and 93.3%) or BAL (54.2% and 86.7%). When combined, SN increased to 68.2% and SP decreased to 76.7%. Diagnostic yield for interstitial pneumonia and chronic inflammation was relatively high but poor for tuberculosis and sarcoidosis. Conclusions: TBNA had the highest SN and SP in diagnosing the various nonneoplastic lesions. However, BAL and BB are useful and complementary tools in the definitive diagnosis of localized and diffuse pulmonary infections.

BACKGROUND: Patients with chronic kidney disease are commonly excluded from clinical trials. The impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer has not been previously studied. OBJECTIVE: This study aimed to investigate the impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer. DESIGN: This is a multi-institutional, retrospective cohort study. SETTINGS: This study was conducted at academic and community cancer centers participating in the Canadian Health Outcomes Research Database Consortium Rectal Cancer Database. PATIENTS: Consecutive patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were selected. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, pathologic complete response, and neoadjuvant chemotherapy/radiotherapy completion rate were the primary outcomes measured. RESULTS: A total of 1254 patients were included. Median age was 62, and 29%/69% had clinical stage II and III disease. Median estimated creatinine clearance was 93 mL/min, with 11%

The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.