The field of hernia surgery has seen many recent advances and continues to evolve. Care of the hernia patient begins preoperatively by ensuring adequate preparation for surgery with surgeons now ...having the opportunity to accurately predict risk which can aid with informed consent. Imaging studies can now help surgeons diagnose and plan hernia surgery on an individual level based on hernia characteristics as well as abdominal wall musculature. In the operating room, new technology and surgical techniques have allowed surgeons to become increasingly sophisticated with goals of reducing tension on midline closures, utilizing minimally invasive and robotic techniques, and availability of new and varied mesh prosthetics. While modest improvements in outcomes have been witnessed by these advances, there is still opportunity for improvement which will be realized by continued research, use of registries, and education and training. Hernia prevention strategies focusing on minimally invasive surgery, laparotomy closure, and the use of prophylactic mesh will also help with the burden of incisional hernias. These advances in hernia surgery have led to the new field of Abdominal Core Health which helps represent this evolving and growing new subspecialty of general surgery.
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2.
Tissue Penetration of Antifungal Agents FELTON, Timothy; TROKE, Peter F; HOPE, William W
Clinical Microbiology Reviews,
01/2014, Volume:
27, Issue:
1
Journal Article
Modern medicine is threatened by the global rise of antibiotic resistance, especially among Gram-negative bacteria. Metallo-β-lactamase (MBL) enzymes are a particular concern and are increasingly ...disseminated worldwide, though particularly in Asia. Many MBL producers have multiple further drug resistances, leaving few obvious treatment options. Nonetheless, and more encouragingly, MBLs may be less effective agents of carbapenem resistance
, under zinc limitation, than
Owing to their unique structure and function and their diversity, MBLs pose a particular challenge for drug development. They evade all recently licensed β-lactam-β-lactamase inhibitor combinations, although several stable agents and inhibitor combinations are at various stages in the development pipeline. These potential therapies, along with the epidemiology of producers and current treatment options, are the focus of this review.
This article provides a perspective on the current status of drug therapy for invasive fungal diseases, together with priorities for the future development of novel compounds. Key opportunities for ...new drugs include production of orally bioavailable agents for the treatment of invasive aspergillosis, invasive candidiasis, cryptococcal meningitis and mucosal and urinary Candida infections. Orally bioavailable agents for the treatment of chronic pulmonary and allergic aspergillosis are also required, as well as new potent drugs against a range of medically important moulds. Antifungal resistance is a problem in certain contexts, but is generally less of a problem than bacterial infections. Earlier and more complete mycological diagnosis and improvements in underlying risk estimation will improve outcomes. The limitations of the current antifungal agents and opportunities for new developments are discussed.
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Therapeutic drug monitoring (TDM) may be required to achieve optimal clinical outcomes in the setting of significant pharmacokinetic variability, a situation that applies to a number of anti-mould ...therapies. The majority of patients receiving itraconazole should routinely be managed with TDM. Voriconazole exhibits highly variable inter-individual pharmacokinetics, and a trough concentration of 1.0-5.5 mg/L is widely accepted although it is derived from relatively low-quality evidence. The case for TDM of posaconazole is currently in a state of flux following the introduction of a newer tablet formulation with improved oral bioavailability, but it may be indicated when used for either prophylaxis or treatment of established disease. The novel broad-spectrum azole drug isavuconazole does not currently appear to require TDM but 'real-world' data are awaited and TDM could be considered in selected clinical cases. For both polyene and echinocandin agents, there are insufficient data regarding the relationship between serum concentrations and therapeutic outcomes to support the routine use of TDM. A number of practical challenges to the implementation of TDM in the treatment of invasive mould infections remain unsolved. The delivery of TDM as a future standard of care will require real-time measurement of drug concentrations at the bedside and algorithms for dosage adjustment. Finally, measures of pharmacodynamic effect are required to deliver therapy that is truly individualized.
Traditional antibiotic dosing was not designed for today's escalating antibiotic resistance, lack of novel antibiotics and growing complexity in patient populations. Dosing that ensures optimal ...antibiotic exposures should be considered essential to increase the likelihood of effective patient treatment. Given the variability in these exposures across different patients, a 'one-dose-fits-all' approach is increasingly problematic. Therapeutic drug monitoring (TDM) of the β-lactams, the most widely used antibiotic class, is underutilized in certain populations. Clinical experience with β-lactam TDM remains relatively scarce. Patients most likely to benefit from such an intervention include the critically ill, the obese, the elderly and those with cystic fibrosis. Most centres actively performing β-lactam TDM target a minimum 100% of the time during the dosing interval that the free (unbound) concentration of antibiotic exceeds the MIC of the pathogen (100% fT>MIC), which is higher than a traditional target supported by in vitro data. Ideally, isolated pathogens should undergo MIC testing along with TDM on a regular basis, allowing clinicians to address the triad of bug, drug and patient ('mug') in equal measure.
Background
Umbilical and epigastric hernias are among the top three most common hernia surgeries performed in the USA with varied techniques. The European and Americas Hernia Societies (EAHS) ...recently published guidelines for repair of umbilical and epigastric hernias. We evaluated how closely the general surgeons of the Abdominal Core Health Quality Collaborative (ACHQC) follow these guidelines and to identify areas for possible improvement.
Method
Data from patients undergoing elective and emergent umbilical or epigastric hernia repair from 2013 to 2021 were extracted from the ACHQC database. The procedures performed on eligible subjects were compared to those proposed by the EAHS guidelines. Data was reported as a percentage and a cutoff of 70% was selected to determine compliance.
Results
Based on these criteria, 11,088 patients were included and most of the recommendations, including appropriate preoperative antibiotic dosing (96.1% umbilical; 97.2% epigastric), permanent mesh selection (umbilical 97.8%; 96.1 epigastric), mesh fixation with suture (83.6% umbilical; 75.5% epigastric), use of mesh for open repair of hernias greater than 1 cm (83.6 umbilical; 85.7 epigastric), and primary defect closure during open (98.6% umbilical; 97.5% epigastric) and laparoscopic (99.6% umbilical; 100% epigastric) repair, were met.
Discussion
Surgeons of the ACHQC adhere to most of the published guidelines on umbilical and epigastric hernia repair. Further research is needed to reinforce or modify the existing recommendations. Standardization of surgical approach will facilitate additional research needed to improve procedural efficiency, while reducing negative outcomes and cost.
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Summary Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected ...by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes include altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.
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Background Operative intervention to correct incisional hernia affects 150,000 patients annually, with 1 in 3 repairs recurring within 9 years. The aim of this study was to compare the incidence of ...incisional hernia and postoperative complications in elective midline laparotomy patients after the use of prophylactic mesh placement and primary suture closure. Methods A systematic review was performed to identify studies comparing prophylactic mesh placement to primary suture closure in elective, midline laparotomy at index abdominal aponeurosis closure. The primary outcome was incisional hernia. Secondary outcomes included postoperative complications. Results Fourteen studies were included (2,114 patients), with 1,152 receiving prophylactic mesh placement. Prophylactic mesh placement decreased the risk of incisional hernia overall when compared to primary suture closure (relative risk = 0.15; P < .00001) and in trials using only polypropylene mesh versus 4:1 primary suture closure (relative risk = 0.15; P = .003). Prophylactic mesh placement reduced the risk of incisional hernia regardless of mesh location or composition: onlay (relative risk = 0.07; P < .0001), retrorectus (relative risk = 0.04; P = .002), and preperitoneal (relative risk = 0.18; P = .02). Prophylactic mesh placement increased risk of seroma overall (relative risk = 1.95; P < .0001), onlay (relative risk = 2.43; P = .01) and preperitoneal (relative risk = 1.47; P = .01) but not retrorectus plane (relative risk = 1.55; P = .26). Polypropylene mesh increased seroma risk only in the onlay position (relative risk = 2.77; P = .04). Prophylactic mesh placement patients are at increased risk for chronic wound pain compared to primary suture closure (relative risk = 1.70; P = .03). Conclusion Prophylactic mesh placement is associated with an 85% postoperative incisional hernia risk reduction when compared to primary suture closure in at-risk patients undergoing elective, midline laparotomy closure. This technique appears to be safe with comparable complication profiles, barring an increased risk of seroma, especially with the onlay technique, and the possibility for an increased risk of chronic pain. Despite this verification, evidence from large domestic trials that sufficiently addresses major knowledge gaps is simply lacking.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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