A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation.

Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

The surgeon as the most important factor in lymph node harvest during axillary clearance.

BACKGROUND: Current guidelines state that 10 or more lymph nodes (LNs) must be harvested in over 90% of axillary lymph node dissections (ALND), with the implication that 'more is better' during axillary surgery. PATIENTS AND METHODS: Our study included all consecutive patients from April 2010 - August 2011 at an NHS Trust (UK) who underwent ALND with the intention of clearing the axilla of LNs (level III). Data regarding harvested LNs were recorded in electronic patient records for each ALND operation. The names of the surgeon and reporting histopathologist were recorded, as well as data regarding preoperative neoadjuvant chemotherapy, prior sentinel lymph node biopsy (SLNB), and number of metastatic LNs. Statistical significance for continuous data was evaluated using unpaired t-test. Pearson correlation coefficient was used to assess the relationship between total number of LNs harvested and number of metastatic LNs. RESULTS: A total of 232 patients underwent 237 ALND operations; 5/232 (2.2%) underwent bilateral surgery. The mean age (range) was 59.9 (32-94) years; the mean number of LNs (range) excised was 13.1 (0-35). The number of identified LNs was independent of whether the patient had undergone previous SLNB, or had received neoadjuvant chemotherapy. The number of LNs was independent of the histopathologist; however, there was a significant difference between surgeons (p<0.001). There was no statistically significant correlation between the total number of LNs harvested and the number of metastatic LNs harvested (r=0.301; p=0.297). CONCLUSION: When auditing practice against guidelines for the treatment of the axilla in breast cancer, the surgeon undertaking ALND appears to be the only significant variable in affecting the completeness of dissection. However, the number of nodes harvested is unrelated to the number of metastatic nodes, challenging the idea that 'more is better' when it comes to axillary surgery.

Factors predicting trastuzumab-related cardiotoxicity in a real-world population of women with HER2+ breast cancer.

BACKGROUND: Trastuzumab may improve disease-free survival after chemotherapy for HER2-positive breast cancer. However, it carries a risk of cardiotoxicity and counseling patients about such risks is part of informed consent. The National Institute for Health and Clinical Excellence has published guidelines for cardiac assessment before and during treatment with trastuzumab in order to minimize the risk of cardiotoxicity. The aim of the present study was to identify risk factors for cardiotoxicity attributed to trastuzumab in a cohort population treated for primary and metastatic breast cancer. PATIENTS AND METHODS: This study included all women who started a course of trastuzumab from February 2006 - February 2011 at three NHS Trusts in the UK. Their cardiac function during treatment was recorded and cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) ≥ 10% and a reduction to <50%, or a clinical reduction in cardiac function as defined by the New York Heart Association. An independent samples t-test was used to assess whether patient age predicted cardiotoxicity. Pearson's chi-squared tests of independence were used to investigate the association between cardiotoxicity, the indication for trastuzumab, exposure to anthracycline chemotherapy, and Adult Comorbidity Evaluation-27 index (ACE-27) scores. RESULTS: There were 388 female patients included in this study, with a mean age of 54 (range = 25-100 years). Cardiotoxicity was recorded during 61 (15.72%) courses of trastuzumab treatment. There were no associations between cardiotoxicity and the three factors (indication, exposure to anthracyclines, or ACE-27 score), and no significant difference in age between patients with and those without cardiotoxicity. However, subgroup analysis of patients who experienced cardiotoxicity (n = 61) showed that there was a negative correlation (-0.455; p = 0.001) between time-to-first cardiotoxicity event and age in the group who had received concurrent anthracycline therapy (n=49). CONCLUSION: In a real-world 5-year population of patients who received trastuzumab, the incidence of drug-related cardiotoxicity was higher than expected, and the age of the patients appeared to predict the first cardiotoxic event amongst those who experienced cardiotoxicity and had received prior anthracyclines. However, incidence of cardiotoxicity in the whole cohort did not appear to be predicted by age, comorbidity, indication, or exposure to anthracylines. Vigilance, therefore, seems justified when conducting cardiac surveillance for all patients during treatment with trastuzumab, but especially for those who are elderly and receiving concurrent anthracycline therapy.

Randomized trial comparing Quixil surgical sealant with Kaltostat hemostatic dressing to control suture line bleeding after carotid endarterectomy with ePTFE patch reconstruction.

Following carotid endarterectomy (CEA), patch angioplasty provides a significant reduction in the risk of perioperative complications. The expanded polytetrafluoroethylene (ePTFE) patch is strong, is resistant to infection, and has low thrombogenicity; but it remains unpopular because of its tendency of prolonged bleeding at the suture line. We aimed to investigate whether the application of Quixil sealant to the suture line could improve the time to achieve hemostasis and reduce local blood loss when compared to a standard topical hemostat Kaltostat. A prospective, randomized trial of 20 patients undergoing CEA was undertaken. Patients were randomized to receive either Quixil sealant (treatment group) or topical Kaltostat (controls) as a hemostatic agent to the patch suture line. Hemostasis was defined as no bleeding at the suture line for 1 minute. Statistical analysis was performed using the Mann-Whitney test. The two groups had a similar age and sex distribution. The mean age was 71 years, and there were seven men and three women in each group. The time to achieve hemostasis was significantly lower in the Quixil group (median 2.5 minutes, range 1-4 minutes) compared to the controls (median 17 minutes, range 7-59 minutes) (p < 0.001). Blood loss after clamp release was also significantly reduced in the Quixil group; median 24.5 ml (range 5.5-105.0 ml) versus 203 ml (range 54.5-817.0 ml) (p < 0.001). This study has demonstrated that Quixil human surgical sealant is an effective sealant of ePTFE patch suture holes and does not compromise the patch repair. It could be used during other vascular procedures involving ePTFE.

Surgery of popliteal artery aneurysms: a 12-year experience.

BACKGROUND: Management of asymptomatic popliteal aneurysm is controversial, and the prognosis for acutely thrombosed aneurysm is notoriously poor. We evaluated the management and outcome for popliteal aneurysm. PATIENTS AND METHODS: A retrospective review of all patients with popliteal aneurysm between 1988 and 2000 was carried out. Fifty-two limbs were operated on in 41 patients. Data collected included findings at presentation, operative details, graft patency, limb salvage, complications, and 30-day mortality. RESULTS: Initial findings included acute ischemia (n = 14), no symptoms (n = 29), acute rupture (n = 2), chronic ischemia (n = 5), and symptoms of nerve or vein compressive (n = 2). All patients with symptomatic aneurysms and 22 patients with asymptomatic aneurysms (21 larger than 2 cm in diameter, 1 with thrombus at duplex ultrasound scanning) underwent surgery as first-line treatment. Of the 7 patients with asymptomatic aneurysm managed with surveillance with duplex ultrasound scanning, acute ischemia developed in three, 1 aneurysm ruptured, compressive symptoms developed in 1, and 2 remained asymptomatic but required surgery because of aneurysm enlargement (>2 cm). Of the 17 patients with acute ischemia, 13 had neurologic signs and underwent immediate thromboembolectomy (trifurcation alone in 8, ankle-level arteriotomy in 4) and bypass grafting (n = 12) or inlay grafting (n = 1), and the other 4 underwent intra-arterial thrombolysis initially. Of these 4 procedures, 2 were successful and had elective surgery; the other 2 required urgent surgery because of secondary distal embolism and failure of recanalization. Thirteen of the 17 grafts were to the crural vessels. Bypass grafting (medial approach) was used in 16 of the 17 patients with acute ischemia, all 5 patients with chronic ischemia, and the 8 patients with no symptoms. An inlay technique (posterior approach) was used in 16 patients with no symptoms, the 3 patients with symptoms of nerve or vein compression, and 1 patient with acute ischemia. The distal anastomoses were to the below-knee popliteal artery in 35 patients and the crural arteries in 15 patients, using autologous vein. Two of the patients with rupture underwent ligation alone, the other undergoing bypass grafting in addition. The overall 5-year primary patency rate was 69%, secondary patency rate was 87%, and limb salvage rate was 87%. Limb salvage was achieved in 14 of the 17 patients with acute ischemia. Patients with asymptomatic aneurysms had better secondary graft patency (100%) compared with symptomatic aneurysms (74%; P <.01). Acute ischemia, technique used, and crural artery grafts were not predictors of graft failure with either univariate or multivariate analysis. Symptomatic aneurysms were associated with more postoperative complications and greater 30-day mortality (4 of 28 vs 0 of 24). CONCLUSION: Thromboembolectomy followed by crural bypass grafting is an effective treatment for popliteal aneurysm with severe acute limb ischemia. Outcome is better with surgical management of asymptomatic popliteal aneurysm compared with symptomatic aneurysm.

Composite sequential grafts for femorocrural bypass reconstruction: experience with a modified technique.

BACKGROUND: To evaluate the efficacy of a modification of the composite sequential femorocrural bypass graft that we adopted in 1985, a retrospective case-note study was undertaken. The grafts combined a prosthetic femoropopliteal section with a popliteal to crural section with autologous vein, linked via a common intermediate anastomosis sited on the above-knee popliteal artery. PATIENTS AND METHODS: Between 1985 and 2000, 68 grafts of this type were constructed in 65 patients with critical ischemia of the lower limb and insufficient autologous vein for construction of an all venous bypass. Reasons for insufficient long saphenous vein included previous lower limb bypass in 33 cases, phlebitis in 16 cases, venous hypoplasia in eight cases, and previous varicose vein surgery in seven cases. Distal anastomoses were carried out to the peroneal artery in 26 cases, the anterior tibial artery in 17 cases, the posterior tibial artery in 17 cases, and the pedal arteries in eight cases. Sources of vein included the long saphenous vein in 26 cases, the arm vein in 38 cases, and the short saphenous vein in two cases. In 22 limbs (32%), angiography had shown an occluded segment of above-knee popliteal artery, and in these cases, local popliteal disobliteration was performed to receive the composite anastomosis and to provide additional outflow. RESULTS: The 2-year cumulative primary patency, secondary patency, and limb salvage rates were 68%, 73%, and 75%, respectively. Localized popliteal disobliteration did not compromise graft patency (P =.07, with log-rank test). CONCLUSION: In the absence of sufficient autologous vein, patients needing bypass to crural arteries can be offered reconstruction with composite sequential grafting with satisfactory results. Furthermore, an occluded above-knee popliteal segment is not a contraindication for composite sequential bypass reconstruction.