Clinical Characteristics and Outcomes in Patients with COVID-19 and Cancer: a Systematic Review and Meta-analysis

Much of routine cancer care has been disrupted due to the perceived susceptibility to SARS-CoV-2 infection in cancer patients. Here, we systematically review the current evidence base pertaining to the prevalence, presentation and outcome of COVID-19 in cancer patients, in order to inform policy and practice going forwards. A keyword-structured systematic search was conducted on Pubmed, Cochrane, Embase and MedRxiv databases for studies reporting primary data on COVID-19 in cancer patients. Studies were critically appraised using the NIH National Heart, Lung and Blood Institute's quality assessment tool set. The pooled prevalence of cancer as a co-morbidity in patients with COVID-19 and pooled in-hospital mortality risk of COVID-19 in cancer patients were derived by random-effects meta-analyses. In total, 110 studies from 10 countries were included. The pooled prevalence of cancer as a co-morbidity in hospitalised patients with COVID-19 was 2.6% (95% confidence interval 1.8%, 3.5%, I²: 92.0%). Specifically, 1.7% (95% confidence interval 1.3%, 2.3%, I²: 57.6.%) in China and 5.6% (95% confidence interval 4.5%, 6.7%, I²: 82.3%) in Western countries. Patients most commonly presented with non-specific symptoms of fever, dyspnoea and chest tightness in addition to decreased arterial oxygen saturation, ground glass opacities on computer tomography and non-specific changes in inflammatory markers. The pooled in-hospital mortality risk among patients with COVID-19 and cancer was 14.1% (95% confidence interval 9.1%, 19.8%, I²: 52.3%). We identified impeding questions that need to be answered to provide the foundation for an iterative review of the developing evidence base, and inform policy and practice going forwards. Analyses of the available data corroborate an unfavourable outcome of hospitalised patients with COVID-19 and cancer. Our findings encourage future studies to report detailed social, demographic and clinical characteristics of cancer patients, including performance status, primary cancer type and stage, as well as a history of anti-cancer therapeutic interventions.     

Elastographic measurements of in-vivo radiofrequency ablation lesions of the kidney

BACKGROUND AND PURPOSE: Elastography may prove useful for monitoring radiofrequency ablative (RFA) therapy because heat-ablated tissues are more elastic than untreated tissues. Herein, we report our initial evaluations of the reliability of elastography for delineating thermal-lesion boundaries at the time of RFA of porcine kidneys. MATERIALS AND METHODS: In-vivo RFA was performed on 20 kidneys from 10 40-kg female pigs. Elastography was performed at the time of surgery and after 48 hours. The imaging plane was perpendicular to the axis of the RF electrode so that the ablated region was around the center of the plane. Measurements of the sections representing the same image plane used for elastography were taken at pathologic examination and compared with the measurements obtained from the elastograms. RESULTS: We found a statistically significant correlation between elastography and pathology measurements with respect to the area and volume estimates (r = 0.9302 and r = 0.953, respectively). Overall, elastography slightly underestimated the lesion size, as judged by the digitalized pathologic images, a finding consistent with previous reports. CONCLUSION: We found a correlation between the area and volume estimates of thermal lesions that were based on elastographic images and the measurements from gross pathologic dimensions. A significant limitation of renal RFA is the inaccuracy of current imaging modalities to provide real-time monitoring, and elastography may prove to be reliable for delineating the resulting thermal lesions.     

The current role of cryotherapy for renal and prostate tumors

Minimally invasive treatments continue to evolve as an alternative method for the treatment of kidney and prostatic tumors. Of the mainstream ablative procedures reported in the literature, the cryotherapy data appear to be the most durable. Currently, select kidney and prostatic lesions are treated using cryotherapy. Although limited long-term survival data using cryotherapy are available, recent series have provided compelling results, promoting interest in renal and prostatic cryoablation. This article assesses the current status of cryotherapy in urology, specifically the indications, techniques, and clinical results in treating kidney and prostate tumors.     

Efficacy and safety of aceclofenac in the treatment of osteoarthritis: a randomized double-blind comparative clinical trial versus diclofenac - an Indian experience

OBJECTIVE: Osteoarthritis is one of the most common forms of arthritis seen in primary care. Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of osteoarthritis. However, gastrointestinal (GI) side effects limit their use. Cyclooxygenase-2 (COX-2) selective inhibitors exhibit better GI tolerability than conventional NSAIDs, but their cardiovascular safety is controversial. An NSAID with high efficacy, high GI tolerability and devoid of adverse cardiovascular effects is therefore a profile preferred by physicians. Aceclofenac is an anti-inflammatory and analgesic drug with preferential COX-2 inhibition. The objective of this study was to assess the efficacy and safety of aceclofenac in the treatment of osteoarthritis in an Indian population. RESEARCH DESIGN AND METHODS: The trial was controlled, comparative, randomized, and double-blind. The study included 247 patients (82 males and 165 females, 40-82 years), suffering from osteoarthritis. Patients were randomized to receive either aceclofenac (100 mg twice daily) or diclofenac (75 mg twice daily). MAIN OUTCOME MEASURES: Clinical assessment was done at screening, randomization, and at 2 weeks, 4 weeks and 8 weeks of treatment by calculating Western Ontario MacMaster (WOMAC) scores, time taken to walk 100 feet, visual analogue scores for pain, investigator's assessment on a Likert scale and joint tenderness. Tolerability assessment was based on adverse events. Patient compliance was also assessed. RESULTS: Aceclofenac was found to be statistically superior to diclofenac in efficacy parameters of WOMAC scores, investigator's assessment and joint tenderness. Aceclofenac was found to be statistically superior to diclofenac in terms of epigastric discomfort, dyspepsia and abdominal pain. Compliance was also better with aceclofenac. The overall response of patients' osteoarthritis to aceclofenac was found to be statistically superior to diclofenac by both physician and patient. CONCLUSIONS: Aceclofenac is an effective and well-tolerated drug in osteoarthritis in the Indian setting.     

Monte Carlo techniques for scattering foil design and dosimetry in total skin electron irradiations

Total skin electron irradiation (TSEI) with single fields requires large electron beams having good dose uniformity, dmax at the skin surface, and low bremsstrahlung contamination. To satisfy these requirements, energy degraders and scattering foils have to be specially designed for the given accelerator and treatment room. We used Monte Carlo (MC) techniques based on EGS4 user codes (BEAM, DOSXYZ, and DOSRZ) as a guide in the beam modifier design of our TSEI system. The dosimetric characteristics at the treatment distance of 382 cm source-to-surface distance (SSD) were verified experimentally using a linear array of 47 ion chambers, a parallel plate chamber, and radiochromic film. By matching MC simulations to standard beam measurements at 100 cm SSD, the parameters of the electron beam incident on the vacuum window were determined. Best match was achieved assuming that electrons were monoenergetic at 6.72 MeV, parallel, and distributed in a circular pattern having a Gaussian radial distribution with full width at half maximum = 0.13 cm. These parameters were then used to simulate our TSEI unit with various scattering foils. Two of the foils were fabricated and experimentally evaluated by measuring off-axis dose uniformity and depth doses. A scattering foil, consisting of a 12 x 12 cm2 aluminum plate of 0.6 cm thickness and placed at isocenter perpendicular to the beam direction, was considered optimal. It produced a beam that was flat within +/-3% up to 60 cm off-axis distance, dropped by not more than 8% at a distance of 90 cm, and had an x-ray contamination of <3%. For stationary beams, MC-computed dmax, Rp, and R50 agreed with measurements within 0.5 mm. The MC-predicted surface dose of the rotating phantom was 41% of the dose rate at dmax of the stationary phantom, whereas our calculations based on a semiempirical formula in the literature yielded a drop to 42%. The MC simulations provided the guideline of beam modifier design for TSEI and estimated the dosimetric performance for stationary and rotational irradiations.     

Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1

Transient receptor potential vanilloid 1 (TRPV1), a ligand-gated cation channel highly expressed in small-diameter sensory neurons, is activated by heat, protons, and capsaicin. The phosphorylation of TRPV1 provides a versatile regulation of intracellular calcium levels and is critical for TRPV1 function in responding to a pain stimulus. We have previously reported that cyclin-dependent kinase 5 (Cdk5) activity regulates nociceptive signaling. In this article we report that the Cdk5-mediated phosphorylation of TRPV1 at threonine-407 can modulate agonist-induced calcium influx. Inhibition of Cdk5 activity in cultured dorsal root ganglia neurons resulted in a significant reduction of TRPV1-mediated calcium influx, and this effect could be reversed by restoring Cdk5 activity. Primary nociceptor-specific Cdk5 conditional-knockout mice showed reduced TRPV1 phosphorylation, resulting in significant hypoalgesia. Thus, the present study indicates that Cdk5-mediated TRPV1 phosphorylation is important in the regulation of pain signaling.     

Concurrent acute generalized exanthematous pustulosis in siblings

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction triggered in most cases by drugs. It is characterized by abrupt onset and rapid evolution of fields of sterile pustules on an erythematous background. The role of genetic predisposition in this reactive disorder is being explored. We report the simultaneous occurrence of AGEP in two siblings after being exposed to the same drug.