Managing the open abdomen in a district general hospital

Introduction

The need to manage an open abdomen is becoming more common in general surgical practice and a variety of methods of temporary abdominal closure (TAC) are available. The evidence for the efficacy of the various forms of TAC as well as the subsequent definitive fascial closure (DFC) rates and complications comes mainly from large trauma series in the US, which represent a different patient population to those in the UK in whom TAC is usually required.

Methods

All cases of open abdomen management in our hospital over a five-year period were reviewed to ascertain the methods of TAC used, our success in achieving DFC and the applicability of managing such cases in a district hospital environment.

Results

Nineteen patients underwent TAC, with two deaths (10.5%) and an overall DFC rate at hospital discharge of 12/17 (70.6%). The median lengths of critical care and hospital stays were 19.5 and 38.0 days respectively. Thirteen out of seventeen survivors had at least one significant complication.

Conclusions

The management of the open abdomen can be achieved safely in a district general hospital setting with acceptable outcomes for the non-trauma patients commonly seen in UK practice but it is a resource intensive and expensive undertaking.     

Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice

Rationale

Patients suffering from Alzheimer’s disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces. Hallmark pathological changes in AD include the aggregation of amyloid-β (Aβ), tau protein hyperphosphorylation as well as pronounced neurodegeneration, neuroinflammation, neurotoxicity and oxidative damage.

Objectives

The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.

Materials and methods

Thus we determined the therapeutic-like effects of chronic CBD treatment (20 mg/kg, daily intraperitoneal injections for 3 weeks) on the APP_swe/PS1?E9 (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including the social preference test, the novel object recognition task and the fear conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours in the elevated plus maze.

Results

Vehicle-treated APPxPS1 mice demonstrated impairments in social recognition and novel object recognition compared to wild type-like mice. Chronic CBD treatment reversed these cognitive deficits in APPxPS1 mice without affecting anxiety-related behaviours.

Conclusions

This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model. Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Factors associated with PrEP awareness according to age and willingness to use HIV prevention technologies: the 2017 online survey among MSM in Brazil*

ABSTRACT

Brazil has the largest population of individuals living with HIV/AIDS in Latin America with a disproportional prevalence of infection among men who have sex with men (MSM). This study evaluated PrEP awareness by age (18–24, 25–35, ≥36 years), its associated factors and the willingness to use HIV prevention technologies among MSM using a GSN app in Brazil. Inclusion criteria were ≥18 years-old, cisgender men and HIV-negative serostatus. Of 7242 individuals, 4136 (57%) completed the questionnaire. PrEP awareness was reported by 51% (though lower among MSM aged 18–24 and ≥36 years) and its associated factors were higher family income, most friends with the same sexual orientation, high number of male sexual partners and marijuana use. HIV testing (never vs. at least once) lead to an almost 3-fold increase in the odds of PrEP awareness. High HIV risk perception led to increased PrEP awareness only among MSM aged 18–24 years. A total of 2335 (56%) was willing to use daily oral PrEP. PrEP awareness remains low in Brazil and mobile tools are key strategies to reach MSM and increase awareness of prevention technologies. Community-based interventions could add to online campaigns to reach the most vulnerable, which include young, non-white and lower-income MSM.     

Genes for skeletal muscle myosin heavy chains are clustered and are not located on the same mouse chromosome as a cardiac myosin heavy chain gene.

Myosin heavy chain (MHC) genes are expressed as several distinct isoforms in a tissue- and stage-specific manner; three skeletal muscle MHC isoforms appear sequentially during development. We have isolated cDNA clones, identified by RNA blot hybridization and by nucleotide sequence determination as coding for portions of the embryonic (pMHC2.2), perinatal (pMHC16.2A), and alpha(V1) cardiac (pMHC141 and pMHC101) MHC isoforms. These four probes and the adult skeletal MHC probe (pMHC32) have been used on Southern blots of genomic DNA to detect restriction fragment length polymorphisms defining the alleles for these genes in mouse species Mus musculus and Mus spretus. In this way, we followed the segregation of skeletal and cardiac MHC genes in 42 offspring resulting from an interspecies backcross. We found that the embryonic, perinatal, and adult skeletal MHC genes are clustered on chromosome 11 near the locus nude, the skeletal and cardiac MHC genes do not cosegregate, and the alpha(V1) cardiac MHC gene is located on chromosome 14 close to Np-1. This result is in contrast to that for other contractile protein genes such as the alkali myosin light chain and the actin multigene families, which are dispersed in the genome.     

Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.     

The factor V B-domain provides two functions to facilitate thrombin cleavage and release of the light chain

Blood coagulation factors V and VIII are homologous proteins that have the domain organization A1-A2-B-A3-C1-C2. Upon thrombin activation, the B-domains of both molecules are released. Previous studies on factor VIII showed that the B-domain was not required for thrombin cleavage or activity. In contrast, deletion of the factor V B-domain (residues 709 to 1545) yielded a molecule with sevenfold reduced procoagulant activity that was not cleaved by thrombin. However, this factor V B- domain deletion molecule was activated by factor Xa, although the fold- activation was 85% that of wild-type factor V. Thrombin cleavage of factor V occurs initially after residue 709 and subsequently after residues 1018 and 1545. The requirement for thrombin cleavage within the B-domain at residue 1018 was evaluated by mutagenesis of Arg1018 to Ile. In the resultant R1018I mutant, the rate of thrombin activation and appearance of maximal cofactor activity was delayed and was consistent with delayed cleavage of the light chain at residue 1545. In contrast, the rate of factor Xa activation in the R1018I mutant was not altered. This finding suggests that thrombin cleavage at 1018 facilitates subsequent thrombin cleavage at 1545. Further mutagenesis was used to study the requirement for sequences within the factor V B- domain for thrombin cleavage at residue 1545. Whereas the factor V deletion molecule removing residues 709 to 1545 was not cleaved by thrombin, a smaller B-domain deletion molecule (residues 709 to 1476) containing an acidic amino acid-rich region (residues 1490 to 1520) was effectively cleaved by thrombin. These results show that residues 1476 to 1545, which contain an acidic amino acid-rich region, were required for thrombin cleavage of the light chain. Introduction of an acidic amino acid-rich region from factor VIII (residues 337 to 372) into the factor V 709 to 1545 deletion also restored thrombin cleavage of the light chain. In contrast, similar replacement with the acidic region from the factor VIII light chain (residues 1649 to 1689) was significantly less effective in promoting thrombin cleavage of the light chain. This finding suggests that the different acidic regions in factors V and VIII are not functionally equivalent in their interaction with thrombin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective non-operative management of civilian gunshot wounds to the abdomen: A systematic review of the evidence

Background

Selective non-operative management (SNOM) of penetrating abdominal wounds has become increasingly common in the past two or three decades and is now accepted as routine management for stab wounds. Gunshot wounds are more frequently managed with mandatory laparotomy but recently SNOM has been successfully applied. This review systematically appraises the evidence behind SNOM for civilian abdominal gunshot wounds.

Methods

A Medline search from 1990 to present identified civilian studies examining success rates for SNOM of abdominal gunshot wounds. Case reports, editorials and abstracts were excluded. All other studies meeting the inclusion criteria of reporting the success rate of non-operative management of abdominal gunshot wounds were analysed.

Results

Sixteen prospective and six retrospective studies met the inclusion criteria, including 18,602 patients with abdominal gunshot wounds. 32.2% (n = 6072) of patients were initially managed non-operatively and 15.5% (n = 943) required a delayed laparotomy. The presence of haemodynamic instability, peritonitis, GI bleeding or any co-existing pathology that prevented frequent serial examination of the abdomen from being performed were indications for immediate laparotomy in all studies. Delayed laparotomy results in similar outcomes to those in patients subjected to immediate laparotomy. Implementation of SNOM reduces the rates of negative and non-therapeutic laparotomies and reduces overall length of stay.

Conclusions

SNOM can be safely applied to some civilian patients with abdominal gunshot wounds and reduces the rates of negative or non-therapeutic laparotomy. Patients who require delayed laparotomy have similar rates of morbidity and mortality and similar length of stay to those patients who undergo immediate laparotomy.     

Hospital Readmissions with Exacerbation of Obstructive Pulmonary Disease in Illicit Drug Smokers

Purpose

Patients with obstructive pulmonary disease (asthma or chronic obstructive pulmonary disease—COPD) who smoke illicit drugs are at an increased risk of hospital admissions. We compared hospital readmission rates due to exacerbations of obstructive pulmonary disease amongst patients who were current/ex-illicit drug smokers versus current/ex-tobacco smokers.

Methods

We reviewed all the admissions between January 2009 and September 2011 with a presumptive diagnosis of an ‘exacerbation of COPD’ retrospectively from our COPD admission database.

Results

There were 950 sequential hospital admissions in 709 patients over a 33-month period; 250 ex-tobacco smokers, 370 current tobacco smokers and 89 current/ex-illicit drug smokers. Recurrent hospital admission rates with exacerbation of obstructive pulmonary disease were higher in the illicit drug smokers compared with current/ex-tobacco smokers (1.00 versus 0.22/0.26, p < 0.001). Illicit drug smokers were younger [50 versus 72.9/69.9 (mean 71.2) years, p < 0.001] and had shorter length of hospital stay [7.44 versus 9.28/10.69 (mean 9.87) days, p = 0.038]. Illicit drug smokers with FEV₁ < 1 litre (L) had higher readmissions than ex/current tobacco smokers with FEV₁ < 1 L (p < 0.001). Admissions requiring non-invasive ventilation for type 2 respiratory failure were more common in illicit drug smokers (8.4 versus 3 %, p < 0.002).

Conclusion

We have shown that readmission rates in illicit drug smokers with FEV₁ < 1 L are higher than in tobacco smokers. Studies are needed to determine whether targeting these illicit drug users with an intensive community intervention package (to include early therapy, pulmonary rehabilitation) will reduce readmission rates in this often neglected population.