Is decolonization to prevent Panton-Valentine leukocidin-positive Staphylococcus aureus infection in the population effective? A systematic review.

Panton-Valentine leukocidin (PVL) -producing Staphylococcus aureus is associated with recurrent skin and soft tissue infections and occasionally invasive infections. There is limited evidence to support current public health guidance on decolonization of cases and household contacts. This systematic review (CRD42020189906) investigated the efficacy of decolonization against PVL-positive S. aureus to inform future public health practice. It included studies of cases with PVL-positive infections providing information on the efficacy of decolonization of cases, carriers, or contacts of cases. Studies were assessed for the risk of bias using the GRADE approach and summarized to inform a narrative synthesis. The search identified 20, mostly observational, studies with small samples and lacking control groups. Studies with longer follow-ups found that, while early post-decolonization screening was negative for most individuals, testing over subsequent months identified re-colonization in some. There is no high-quality evidence to show whether decolonization is effective in reducing (re)infection or long-term carriage of PVL-positive S. aureus and the low-quality evidence available indicates it may not be effective in eradicating carriage or reducing future disease. Furthermore, there may be risks associated with decolonization, e.g., potentially increased risk of infection from other microbes, opportunity costs and negative impacts of repeated testing for asymptomatic carriage. Further research is required to better understand what affects the ability of decolonization efforts to reduce risk to cases and their contacts, including strain, host and environmental factors.

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.

Laparoscopy-assisted gastrectomy in the elderly: experience from a UK centre.

BACKGROUND Gastric cancer has a high incidence in the elderly in the UK, with a significant number of patients aged 75 years or more. While surgery forms the mainstay of treatment, evidence pertaining to the management of gastric cancer in the Western population in this age group is scarce. METHODS We retrospectively reviewed the outcomes of laparoscopy-assisted total and distal gastrectomies at our centre from 2005 to 2015. Patients aged 70 years or above were included in the elderly group. RESULTS A total of 60 patients underwent laparoscopy-assisted gastrectomy over a 10-year period, with a predominance of male patients. There was no significant difference in the rate of overall surgical and non-surgical complications, in-hospital mortality, operation time and length of hospital stay, between the elderly and non-elderly groups. Univariate analysis, performed for risk factors relating to anastomotic leak and surgical complications, showed that age over 70 years and higher American Association of Anesthesiologists grades are associated with a higher, though not statistically significant, number of anastomotic leaks (P = 1.000 and P = 0.442, respectively) and surgical complications (P = 0.469 and P = 0.162, respectively). The recurrence rate within the first 3 years of surgery was significantly higher in the non-elderly group compared with the elderly group (Log Rank test, P = 0.002). There was no significant difference in survival between the two groups (Log Rank test, P = 0.619). CONCLUSIONS Laparoscopy-assisted gastrectomy is safe and feasible in an elderly population. There is a need for well-designed, prospective, randomised studies with quality of life data to inform our practice in future.

Day case laparoscopic cholecystectomy in patients with high BMI: Experience from a UK centre.

INTRODUCTION: Symptomatic gall stones may require laparoscopic cholecystectomy (LC), which is one of the most commonly performed general surgical operations in the western world. Patients with a high body mass index (BMI) are at increased risk of having gall stones, and are often considered at high risk of surgical complications due to their increased BMI. We believe that day case surgery could nevertheless have significant benefits in terms of potential cost savings and patient satisfaction in this population. We therefore compared the outcomes of day case patients undergoing LC stratified by BMI, with a specific focus on the safety and success of the procedure in obese and morbidly obese groups. METHODS: We reviewed a database of day case procedures performed between January 2004 and December 2012, including all patients with symptomatic gall stone disease who underwent LC. The patients were divided in four BMI groups: less than 25 kg/m(2), 25-29 kg/m(2), 30-39 kg/m(2) and 40 kg/m(2) or above. RESULTS: The overall success rate for day case surgery was 78%. There were no significant differences in rates of intra-abdominal collection or readmission with increasing BMI. However, increasing BMI was associated with a significant increase in the rate of wound infection. CONCLUSIONS: LC in patients with a high BMI is safe and can be performed effectively as a day case procedure.

Regulation of early peritoneal neutrophil migration by macrophage inflammatory protein-2 and mast cells in experimental peritonitis.

Neutrophil (PMN) migration into the peritoneal cavity in response to fecal peritonitis is an important mechanism of host defense against bacterial invasion. We show that the murine C-X-C (PMN-specific) chemokine, macrophage inflammatory protein-2 (MIP-2), on intraperitoneal injection in mice, causes PMN migration into the peritoneum. MIP-2 mRNA and protein were expressed by peritoneal leukocytes after cecal ligation and puncture (CLP) in mice and neutralization of MIP-2 reduced peritoneal PMN migration. A prerequisite for neutrophil-endothelial adhesion and subsequent migration from the circulation is selectin-mediated rolling. Pretreatment of mice with an anti-P-selectin antibody before intraperitoneal injection of MIP-2 significantly reduced peritoneal PMN migration. However, there are no reports that a C-X-C chemokine can up-regulate endothelial selectins. We postulated that MIP-2, when injected intraperitoneally, interacts with a cell that is known to release factors that up-regulate endothelial selectins. A likely candidate is the mast cell, which contains histamine and tumor necrosis factor alpha (TNF-alpha), and both of these factors induce selectins. Intraperitoneally injected MIP-2 caused an early significant increase in peritoneal TNF-alpha, whereas histamine levels were unaffected. In a subsequent experiment, mast cell-deficient mice and their normal controls were then injected intraperitoneally with MIP-2 or underwent CLP. Significantly fewer PMNs migrated into the peritoneal cavity in the mast cell-deficient mice after MIP-2 injection or CLP. Thus, our findings indicate that mast cells and MIP-2 are necessary for PMN migration into the peritoneum in response to intra-abdominal infection, and that MIP-2 appears to facilitate this through an increase in TNF-alpha release.

Neutrophil migration into the peritoneum is P-selectin dependent, but sequestration in lungs is selectin independent during peritonitis.

Neutrophil (PMN) influx into the peritoneal cavity in response to bacterial peritonitis is an indispensable aspect of host defense. PMNs also are responsible for the remote organ injury observed after major abdominal infection. The aim of this study was to examine the effect of selectin blockade on PMN migration into the peritoneum and on PMN sequestration in the lungs, early in the course of peritonitis. Cecal ligation and puncture (CLP) was performed on P-selectin-deficient (P-def) mice and their genetic controls (C57). Both groups were treated with anti-E-selectin antibody, anti-L-selectin, or isotypic control immunoglobulin G at the time of CLP. 6 h after CLP, mice were sacrificed. Peritoneal PMN migration decreased in P-def mice compared with C57 controls after CLP. Blockade of E- or L-selectin alone in controls did not alter peritoneal PMN influx or circulating PMNs after CLP. In the P-def mice, treatment with anti-E-antibody or anti-L-antibody nearly eliminated PMN influx into the peritoneum. In contrast, circulating PMNs markedly increased after CLP in P-def mice when compared with baseline values. Lung myeloperoxidase increased in all groups of mice following CLP. Blockade of P-selectin with anti-P-selectin antibody elicited a response similar to that observed in the P-def mice. In conclusion, P-selectin mediates PMN influx into the peritoneal cavity, while E- and L-selectins do not appear to play any significant role in the 6 h time period following CLP. Lung PMN sequestration, after CLP, occurred independent of P-, E-, or L-selectin expression. Blockade of P-selectin during peritonitis appears to be potentially deleterious by preventing early PMN influx into the compartment containing the septic focus.

Neutrophil sequestration in liver and lung is differentially regulated by C-X-C chemokines during experimental peritonitis.

C-X-C chemokines play an important role in the migration and activation of neutrophils (PMNs) during an inflammatory event. We measured mRNA and protein expression of the murine C-X-C chemokines macrophage inflammatory protein-2 (MIP-2) and KC in the lungs, liver, blood, and peritoneal cavity of Swiss Webster mice after cecal ligation and puncture (CLP). Neutralizing antibodies to MIP-2 and KC were also used to determine the biological effects of these chemokines on neutrophil sequestration and organ injury in the CLP model. The data showed that early after CLP, MIP-2 mRNA and protein were expressed predominantly by the lung, whereas KC mRNA and protein were expressed by the liver. Inhibition of MIP-2 reduced both lung neutrophil sequestration and peritoneal neutrophil migration. Inhibition of KC had no effect on overall neutrophil sequestration in liver but reduced injury as measured by serum transaminases. An early survival benefit was found with anti-KC treatment, although overall survival was not different. Our study showed a differential expression by organs of C-X-C chemokines during sepsis and suggested that such chemokine effects are tissue-specific.

The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone. However NAC has adverse effects. We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery. METHODS: We prospectively studied 116 patients with oesophageal or gastric cancer to assess the effect of NAC on physical fitness, of whom 89 underwent cardiopulmonary exercise testing (CPET) before NAC and proceeded to surgery. 39 patients were tested after all cycles of NAC but prior to surgery. Physical fitness was assessed by measuring oxygen uptake (VO2 in ml kg(-1) min(-1)) at the estimated lactate threshold (θL) and at peak exercise (VO2 peak in ml kg(-1) min(-1)). RESULTS: VO2 at θL and at peak were significantly lower after NAC compared to pre-NAC values: VO2 at θL 14.5 ± 3.8 (baseline) vs. 12.3 ± 3.0 (post-NAC) ml kg(-1) min(-1); p ≤ 0.001; VO2 peak 20.8 ± 6.0 vs. 18.3 ± 5.1 ml kg(-1) min(-1); p ≤ 0.001; absolute VO2 (ml min(-1)) at θL and peak were also lower post-NAC; p ≤ 0.001. Decreased baseline VO2 at θL and peak were associated with increased one year mortality in patients who completed a full course of NAC and had surgery; p = 0.014. CONCLUSION: NAC before cancer surgery significantly reduced physical fitness in the overall cohort. Lower baseline fitness was associated with reduced one-year-survival in patients completing NAC and surgery, but not in patients who did not complete NAC. It is possible that in some patients the harms of NAC may outweigh the benefits. Trials Registry Number: NCT01335555.

Heparin-binding protein decreases apoptosis in human and murine neutrophils.

BACKGROUND: Heparin-binding protein (HBP), a serine protease without any known proteolytic activity, is found in human polymorphonuclear leukocyte (PMN) granules, but not in mice. HBP potentiates the endotoxin-induced release of tumor necrosis factor (TNF) alpha, interleukin (IL)-1, and IL-6 from isolated monocytes. HBP has also been shown to increase the survival of cultured monocytes and protect them from oxidative stress. However, whether HBP affects PMNs themselves is not known. MATERIALS AND METHODS: Based on our work with cultured monocytes and the survival benefit noted in experimental peritonitis, we hypothesized that HBP would have a beneficial effect on the survival of neutrophils. We evaluated the effect of HBP on apoptosis in murine peritoneal exudative cells elicited by intraperitoneal thioglycollate administration and in normal human neutrophils from volunteers. Leukocytes were isolated from the peritoneal cavity and blood of mice that underwent intraperitoneal thioglycollate instillation. The mouse peritoneal exudate cells and normal human neutrophils isolated from peripheral blood were used to study the effect of HBP on survival and apoptosis. RESULTS: HBP decreased percentage apoptosis of mouse cells in both serum-enriched (from 24.8 to 4.5%) and serum-deprived (from 23.1 to 8.2%) cultures. In human PMNs, the protective effect of HBP was seen only in the serum-deprived group, with a decrease in percentage apoptosis from 69.1 to 43.3%. CONCLUSIONS: For the first time, we have shown that HBP, in addition to its known augmentation of the proinflammatory response of monocytes, also acts as a prosurvival protein for neutrophils themselves, and thereby enhances local host defense.

Outcome of transplantation using kidneys from controlled (Maastricht category 3) non-heart-beating donors.

BACKGROUND: Many renal transplant centres are reluctant to use kidneys from non-heart-beating (NHB) donors because of the high incidence of primary non-function and delayed graft function reported in the literature. Here, we report our favourable experience of using kidneys from Maastricht category 3 donors (controlled NHB donors). MATERIALS AND METHODS: From January 1996 to June 2002, 42 renal transplants using kidneys from 25 controlled NHB donors were undertaken at our centre. The rates of primary non-function, delayed graft function (DGF), rejection and long-term graft and patient survival were compared with those of 84 recipients of grafts from heart-beating (HB donors) transplanted contemporaneously. RESULTS: Primary non-function did not occur in recipients of grafts from NHB donors but was seen in two grafts from HB donors. DGF occurred in 21 of 42 (50%) kidneys from NHB donors and 14 of 84 (17%) kidneys from HBD donars (p < 0.001). The acute rejection rates in the two groups were similar (33% for grafts from NHB donors vs. 40% from HB donors). By 1 month after transplantation, there was no significant difference in serum creatinine concentration between the two groups. Over a median follow-up period of 32 months (range 2-75 months), the actuarial graft survival rates at 1, 3 and 5 yr after transplantation were 84, 80 and 74% for recipients of kidneys from NHB donors, compared with 89, 85 and 80% for kidneys from HB donors. CONCLUSION: Controlled NHB donors are a valuable and under-used source of kidneys for renal transplantation. The outcome for recipients of kidney allografts from category 3 NHB donors is similar to that seen in recipients of grafts from conventional HB cadaveric donors.