Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.     

Physiological determinants of residual cerebral arterial pulsatility on best medical treatment after TIA or minor stroke

Cerebral arterial pulsatility is strongly associated with cerebral small vessel disease and lacunar stroke yet its dependence on central versus local haemodynamic processes is unclear. In a population-based study of patients on best medical managment, 4–6 weeks after a TIA or non-disabling stroke, arterial stiffness and aortic systolic, diastolic and pulse pressures were measured (Sphygmocor). Middle cerebral artery peak and trough flow velocities and Gosling’s pulsatility index were measured by transcranial ultrasound. In 981 participants, aortic and cerebral pulsatility rose strongly with age in both sexes, but aortic diastolic pressure fell more with age in men whilst cerebral trough velocity fell more in women. There was no significant association between aortic systolic or diastolic blood pressure with cerebral peak or trough flow velocity but aortic pulse pressure explained 37% of the variance in cerebral arterial pulsatility, before adjustment, whilst 49% of the variance was explained by aortic pulse pressure, arterial stiffness, age, gender and cardiovascular risk factors. Furthermore, arterial stiffness partially mediated the relationship between aortic and cerebral pulsatility. Overall, absolute aortic pressures and cerebral blood flow velocity were poorly correlated but aortic and cerebral pulsatility were strongly related, suggesting a key role for transmission of aortic pulsatility to the brain.     

Did quality of life for older cancer survivors improve with the turn of the century in the United States?

ObjectivesAlthough survival after a cancer diagnosis has improved considerably over the past 20 years, little is known about trends in health-related quality-of-life (HRQOL) for older prostate, breast, and lung cancer survivors.MethodsUsing a population-based registry with longitudinal patient reported outcomes (the National Cancer Institute Surveillance, Epidemiology and End Results database linked to Medicare Health Outcomes Survey), we analyzed Medicare Advantage patients diagnosed with cancer during 1998–2011, who completed surveys regarding HRQOL through 2013. ‘Early Era’ patients were treated during 1998–2003; ‘Late Era’ patients were treated during 2006–2011. After propensity score matching, post-diagnosis changes in health utility (HU), Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were calculated and compared between the two eras.ResultWe identified 208 older patients with prostate, 276 with breast and 76 with lung cancer who were treated in the ‘Early Era’ and matched to equal numbers in the ‘Late Era’. Mean age of patients in early and late era was 72 and 73 years, respectively. The mean post-diagnosis decline in health utility for patients treated in the ‘Late Era’ was not significantly different from the ‘Early Era’ for any cancer (Prostate [early vs. late]: ?0.06 vs. -0.03, p = .09; Breast: ?0.03 vs. ?0.04, p = .65; Lung: ?0.07 vs. ?0.07, p = .95); nor for Physical Component Summary or Mental Component Summary scores.ConclusionOlder patients treated for prostate, breast or lung cancer in the later era reported similar outcomes of changes in HRQOL compared to earlier era patients.     

Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016

Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon (Procyon lotor) and striped skunk (Mephitis mephitis) populations impacted by raccoon RV. Field trial evaluations of the Ontario Rabies Vaccine Bait (ONRAB) were initiated to expand ORV products available to meet the rabies management goal of raccoon RV elimination. This study describes the continuation of a 2011 trial in West Virginia. Our objective was to evaluate raccoon and skunk response to ORV occurring in West Virginia for an additional two years (2012–2013) at 75 baits/km² followed by three years (2014–2016) of evaluation at 300 baits/km². We measured the change in rabies virus-neutralizing antibody (RVNA) seroprevalence in targeted wildlife populations by comparing levels pre- and post-ORV during each year of study. The increase in bait density from 75/km² to 300/km² corresponded to an increase in average post-ORV seroprevalence for raccoon and skunk populations. Raccoon population RVNA levels increased from 53% (300/565, 95% CI: 50–57%) to 82.0% (596/727, 95% CI: 79–85%) during this study, and skunk population RVNA levels increased from 11% (8/72, 95% CI: 6–20%) to 39% (51/130, 95% CI: 31–48%). The RVNA seroprevalence pre-ORV demonstrated an increasing trend across study years for both bait densities and species, indicating that multiple years of ORV may be necessary to achieve and maintain RVNA seroprevalence in target wildlife populations for the control and elimination of raccoon RV in the eastern USA.     

Improving the quality of pressure ulcer management in a skilled nursing facility

Pressure ulcers (PUs) are a serious health care problem for nursing home residents and a key quality metric for regulators. Three initiatives were introduced at a 128‐bed facility to improve PU prevention. First, a Quality Assurance and Performance Improvement project and a Root Cause Analysis were conducted to improve the facility's wound care programme. Second, a digital wound care management solution was adopted to track wound management. Third, the role of skin integrity coordinator was created as a central point of accountability for wound care‐related activities and related performance metrics. Improvements in PU prevention were tracked using Centers of Medicare and Medicaid data, specifically (a) the percentage of long‐stay high‐risk residents with PUs and (b) the percentage of short‐stay residents with PUs that are new or have worsened. PU prevalence for long‐stay high‐risk residents was 12.99% (Q4 2016), and upon implementation of these initiatives, the facility saw continued reductions in PU prevalence to 2.9% (Q4 2017), while PUs for short‐stay residents were maintained at zero throughout this period. This study highlights the power of effective management combined with real‐time data analytics, as enabled by digital wound care management, to make significant improvements in health care delivery.     

E‐cadherin and p120ctn protein expression are lost in hidradenitis suppurativa lesions

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease affecting the pilosebaceous units in the axilla, groin and buttocks. While the pathogenesis of HS is not clear, mechanical stress exacerbates HS. In this study, we aimed to determine whether intracellular adhesive junctions may be aberrant in HS patient skin. Strikingly, we observed loss of E‐cadherin and p120ctn protein expression, two key adherens junction proteins, in ~85% of HS severe skin lesions. Moreover, loss of protein expression was apparent in non‐lesional skin from HS patients and the degree of loss positively correlated with HS Hurley Stage of disease. E‐cadherin expression was unaltered in other inflammatory skin conditions including chronic wound epithelium, atopic dermatitis, and acne vulgaris compared with healthy skin suggesting that its loss may be uniquely relevant to HS pathogenesis. A complete loss of α‐catenin, β‐catenin and ZO‐1 was not observed; however, some cytoplasmic staining of the catenins was noted in HS epithelium. We also demonstrated diminished desmosome size in HS lesional skin. Overall, our data suggested that loss of adherens junction proteins and diminished desmosome size in HS skin contributes to the skin's inability to withstand mechanical stress and provides rationale as to why mechanical stress exacerbates HS symptoms.