Laminar flow reduces cases of surgical site infections in vascular patients

Introduction

Numerous strategies are employed routinely in an effort to lower rates of surgical site infections (SSIs). A laminar flow theatre environment is generally used during orthopaedic surgery to reduce rates of SSIs. Its role in vascular surgery, especially when arterial bypass grafts are used, is unknown.

Methods

A retrospective review of a prospectively maintained database was undertaken for all vascular procedures performed by a single consultant over a one-year period. Cases were performed, via random allocation, in either a laminar or non-laminar flow theatre environment. Demographic data, operative data and evidence of postoperative SSIs were noted. A separate subgroup analysis was undertaken for patients requiring an arterial bypass graft. Univariate and multivariate logistical regression was undertaken to identify significant factors associated with SSIs.

Results

Overall, 170 procedures were analysed. Presence of a groin incision, insertion of an arterial graft and a non-laminar flow theatre were shown to be predictive of SSIs in this cohort. In the subgroup receiving arterial grafts, only a non-laminar flow theatre environment was shown to be predictive of an SSI.

Conclusions

This study suggests that laminar flow may reduce incidences of SSI, especially in the subgroup of patients receiving arterial grafts.     

Population Exposure to Phthalate‐containing Drugs

Phthalates are known endocrine disruptors. Not commonly recognized, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of phthalate‐containing drugs in Denmark from 2004 to 2015. National data on annual sale of medications (tablets only) were accessed from medstat.dk. Data from the Danish Medicines Agency on phthalate content per tablet were merged with data on total sale for each active substance and drug formulation. We used the ‘defined daily dose’ (DDD) as the unit of sale and calculated the total amount of phthalate (mg) dispensed per 1000 inhabitants. Specific tablet content was compared with the maximum daily exposure limits defined by regulatory agencies for diethyl phthalate (DEP) and dibutyl phthalate (DBP) of 4.0 and 0.01 mg/kg/day, respectively. Use of phthalate‐containing drugs in Denmark was common. We found 154 drug products containing five different phthalates. Two low‐molecular‐weight phthalates and three high‐molecular‐weight phthalates were identified, with a total sale of 59.4 and 112 DDD per 1000 inhabitants per day during the study period, respectively. The highest amount of DBP was found in multi‐enzymes (24.6–32.8 mg per DDD) and mesalazine (12.5–26.4 mg per DDD). Budesonide, lithium and bisacodyl also exceeded the DBP exposure limit of 0.01 mg/kg/day. Other drugs had high levels of DEP, although not exceeding the exposure limit. Sales of phthalate‐containing drugs in Denmark from 2004 to 2015 were substantial, and phthalate exposure from several products exceeded the regulatory exposure limit introduced in 2014.     

Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases

Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12-13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.     

Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice

The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound-conditioned medium activates caspase-1 and induces release of interleukin (IL)-1β and IL-18 in cultured Mp via a reactive oxygen species–mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from proinflammatory to healing-associated Mp phenotypes, and increased levels of prohealing growth factors. Furthermore, data generated from bone marrow–transfer experiments from NLRP-3 or caspase-1 knockout to db/db mice indicated that blocking inflammasome activity in bone marrow cells is sufficient to improve healing. Our findings indicate that sustained inflammasome activity in wound Mp contributes to impaired early healing responses of diabetic wounds and that the inflammasome may represent a new therapeutic target for improving healing in diabetic individuals.     

Safety Data in Patients with Autoimmune Diseases during Treatment with High Doses of Vitamin D3 According to the “Coimbra Protocol”

Background: In 2013, the group of Cicero Coimbra, Brazil, reported the clinical efficacy of high doses of vitamin D3 in patients suffering from autoimmune skin disorders (“Coimbra protocol”, CP). However, hypercalcemia and the subsequent impaired renal function may be major concerns raised against this protocol. Methods: We report for the first time for a broad spectrum of autoimmune diseases in 319 patients (mean age (±SD) 43.3 ± 14.6 years, 65.5% female, 34.5% male) safety data for high doses of orally applied vitamin D3 (treatment period: up to 3.5 years) accompanied by a strict low-calcium diet and regular daily fluid intake of at least 2.5 L. Results: Mean vitamin D3 dose was 35,291 ± 21,791 IU per day. The measurement of more than 6100 single relevant laboratory parameters showed all mean values (±SD) within the normal range for total serum calcium (2.4 ± 0.1 mmol/L), serum creatinine (0.8 ± 0.2 mg/dL), serum creatinine associated estimated GFR (92.5 ± 17.3 mL/min), serum cystatin C (0.88 ± 0.19 mg/L), serum TSH (1.8 ± 1 mIU/L), and for 24 h urinary calcium secretion (6.9 ± 3.3 mmol/24 h). We found a very weak relationship between the dosage of oral vitamin D3 and the subsequent calcium levels, both in serum and in urinary excretion over 24 h, respectively. Conclusions: Our data show the reliable safety of the CP in autoimmune patients under appropriate supervision by experienced physicians.