The Role of Biologic Mesh and Fundoplication in the Surgical Management of Hiatal Hernias: A Multicenter Evaluation.

INTRODUCTION: Hiatal hernia repair is associated with substantial recurrence of both hiatal hernia and symptoms of gastroesophageal reflux (GER). While small randomized controlled trials demonstrate limited differences in outcomes with use of mesh or fundoplication type, uncertainty remains. METHODS: A multicenter, retrospective review of patients undergoing surgical treatment of hiatal hernias between 2015 and 2020 was performed. Patients with mesh and with suture-only repair were compared, and partial versus complete fundoplication was compared. Primary outcomes were hernia recurrence and occurrence of postoperative GER symptoms and dysphagia. Multivariable regression was performed to assess the effect of each intervention on clinical outcomes. RESULTS: A total of 453 patients from four sites were followed for a median (IQR) of 17 (13) months. On multivariate analysis, mesh had no impact on hernia recurrence (odds ratio 0.993, 95% CI: 0.53-1.87, p = 0.982), and fundoplication type did not impact recurrence of postoperative GER symptoms (complete: odds ratio 0.607, 95% CI: 0.33-1.12, p = 0.112) or dysphagia (complete: odds ratio 1.17, 95% CI: 0.56-2.43, p = 0.677). CONCLUSION: During hiatal hernia repair, mesh and fundoplication type do not appear to have substantial impact on GER symptoms, dysphagia, or hernia recurrence. This multicenter study provides real-world evidence to support the findings of small RCTs.

Updated guideline for closure of abdominal wall incisions from the European and American Hernia Societies.

BACKGROUND: Incisional hernia is a frequent complication of abdominal wall incision. Surgical technique is an important risk factor for the development of incisional hernia. The aim of these updated guidelines was to provide recommendations to decrease the incidence of incisional hernia. METHODS: A systematic literature search of MEDLINE, Embase, and Cochrane CENTRAL was performed on 22 January 2022. The Scottish Intercollegiate Guidelines Network instrument was used to evaluate systematic reviews and meta-analyses, RCTs, and cohort studies. The GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) was used to appraise the certainty of the evidence. The guidelines group consisted of surgical specialists, a biomedical information specialist, certified guideline methodologist, and patient representative. RESULTS: Thirty-nine papers were included covering seven key questions, and weak recommendations were made for all of these. Laparoscopic surgery and non-midline incisions are suggested to be preferred when safe and feasible. In laparoscopic surgery, suturing the fascial defect of trocar sites of 10 mm and larger is advised, especially after single-incision laparoscopic surgery and at the umbilicus. For closure of an elective midline laparotomy, a continuous small-bites suturing technique with a slowly absorbable suture is suggested. Prophylactic mesh augmentation after elective midline laparotomy can be considered to reduce the risk of incisional hernia; a permanent synthetic mesh in either the onlay or retromuscular position is advised. CONCLUSION: These updated guidelines may help surgeons in selecting the optimal approach and location of abdominal wall incisions.

An incisional hernia results from a weakness of the abdominal wall muscles that allows fat from the inside or organs to bulge out. These hernias are quite common after abdominal surgery at the site of a previous incision. There is research that discusses different ways to close an incision and this may relate to the chance of hernia formation. The aim of this study was to review the latest research and to provide a guide for surgeons on how best to close incisions to decrease hernia rates. When possible, surgery through small incisions may decrease the risk of hernia formation. If small incisions are used, it may be better if they are placed away from areas that are already weak (such as the belly button). If the incision is larger than 1 cm, it should be closed with a deep muscle-fascia suture in addition to skin sutures. If there is a large incision in the middle of the abdomen, the muscle should be sutured using small stitches that are close together and a slowly absorbable suture should be used. For patients who are at higher risk of developing hernias, when closing the incision, the muscle layer can be strengthened by using a piece of (synthetic) mesh. There is no good research available on recovery after surgery and no clear guides on activity level or whether a binder will help prevent hernia formation.

Population Pharmacokinetics of Praziquantel in Pregnant and Lactating Filipino Women Infected with Schistosoma japonicum.

An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite Schistosoma spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in areas of endemicity. The World Health Organization recommends that pregnant and lactating women be included in schistosomiasis MDA programs, and several recent studies have evaluated the safety and efficacy of PZQ use during pregnancy. To date, there are no data describing PZQ pharmacokinetics (PK) during pregnancy or among lactating postpartum women. As part of a randomized controlled trial investigating the safety and efficacy of PZQ during human pregnancy, we examined the PK of this therapeutic drug among three distinct cohorts of women infected with S. japonicum in Leyte, Philippines. Specifically, we studied the PK properties of PZQ among early- and late-gestation pregnant women (n = 15 each) and lactating postpartum women (n = 15) with schistosomiasis. We found that women in early pregnancy had increased apparent clearance and lower area-under-the-curve (AUC0-24) values that may be related to physiological changes in drug clearance and/or changes in oral bioavailability. There was no relationship between body weight and apparent clearance. The mean ± standard deviation partition ratio of plasma to breast milk was 0.36. ± 0.13. The estimated median infant PZQ daily dose would be 0.037 mg/kg of body weight ingested from breast milk, which is significantly lower than the dosage required for antischistosomal activity and not known to be harmful to the infant. Our PK data do not support the suggestion to delay breastfeeding 72 h after taking PZQ. Results can help inform future drug efficacy studies in pregnant and lactating women with schistosomiasis.

Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis: a post hoc analysis of the SECURE trial.

Background: Historically, baseline neutropenia and lack of neutrophil recovery have been associated with poor outcomes in invasive aspergillosis (IA). It is unclear how treatment with the new Aspergillus-active triazoles isavuconazole and voriconazole affects outcomes in neutropenic patients with IA. Methods: A post hoc analysis of the Phase 3 SECURE trial assessed patients with neutropenia (neutrophil count <0.5 × 109/L for >10 days at baseline) with IA (proven/probable) who had received either isavuconazole or voriconazole. The primary endpoint was all-cause mortality (ACM) through day 42. ACM in patients with resolved versus unresolved neutropenia at day 7 and overall success at end of treatment (EOT) were also assessed. Results: One hundred and forty-two patients with neutropenia and IA were included (isavuconazole n = 78, voriconazole n = 64). ACM through day 42 (primary endpoint), day 7 and EOT were higher for patients with unresolved versus resolved neutropenia at each timepoint (day 42, unresolved: 45.0% isavuconazole, 45.2% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; day 7, unresolved: 31.0% isavuconazole, 29.8% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; EOT, unresolved: 48.6% isavuconazole, 36.4% voriconazole; resolved: 5.0% isavuconazole, 14.3% voriconazole). ACM was significantly higher for isavuconazole-treated patients with unresolved versus resolved neutropenia (day 7, P = 0.031; day 42, P < 0.001; EOT, P < 0.001). In voriconazole-treated patients, ACM was significantly higher among patients with unresolved versus resolved neutropenia at day 42 (P = 0.002) and numerically higher at day 7 and EOT (P > 0.05 for both). Conclusions: Isavuconazole had comparable efficacy and safety to voriconazole in neutropenic patients with IA. Resolution of neutropenia was associated with improved outcomes.

Population pharmacokinetics of micafungin and its metabolites M1 and M5 in children and adolescents.

The aim of this analysis was to identify therapeutic micafungin regimens for children that produce the same micafungin exposures known to be effective for the prevention and treatment of Candida infections in adults. Pediatric pharmacokinetic data from 229 patients between the ages of 4 months and <17 years were obtained from four phase I and two phase III clinical trials. Population pharmacokinetic models were used to simulate the proportion of children who had a steady-state area under the concentration-time curve at 24 hours (AUC24) of micafungin within the 10th to 90th percentile range observed in a population of adults receiving a dose of micafungin with established efficacy for invasive candidiasis (100 mg/day), i.e., 75 to 139 µg·h/ml. Simulated pediatric dosages of 0.5 to 5 mg/kg of body weight/day were explored. A two-compartment model was used that incorporated body weight as a predefined covariate for allometric scaling of the pharmacokinetic parameters. During construction of the model, aspartate aminotransferase and total bilirubin were also identified as covariates that had a significant effect on micafungin clearance. A dose of 2 mg/kg resulted in the highest proportion of children within the predefined micafungin AUC24 target range for invasive candidiasis. Cutoffs of 40 or 50 kg for weight-based dosing resulted in heavier children being appropriately dosed. Thus, dose regimens of 1, 2, and 3 mg/kg/day micafungin are appropriate for the prevention of invasive candidiasis, the treatment of invasive candidiasis, and the treatment of esophageal candidiasis, respectively, in children aged 4 months to <17 years.

Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology.

The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics-pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents.

Antimicrobial treatment imprecision: an outcome-based model to close the data-to-action loop.

Health-care systems, food supply chains, and society in general are threatened by the inexorable rise of antimicrobial resistance. This threat is driven by many factors, one of which is inappropriate antimicrobial treatment. The ability of policy makers and leaders in health care, public health, regulatory agencies, and research and development to deliver frameworks for appropriate, sustainable antimicrobial treatment is hampered by a scarcity of tangible outcome-based measures of the damage it causes. In this Personal View, a mathematically grounded, outcome-based measure of antimicrobial treatment appropriateness, called imprecision, is proposed. We outline a framework for policy makers and health-care leaders to use this metric to deliver more effective antimicrobial stewardship interventions to future patient pathways. This will be achieved using learning antimicrobial systems built on public and practitioner engagement; solid implementation science; advances in artificial intelligence; and changes to regulation, research, and development. The outcomes of this framework would be more ecologically and organisationally sustainable patterns of antimicrobial development, regulation, and prescribing. We discuss practical, ethical, and regulatory considerations involved in the delivery of novel antimicrobial drug development, and policy and patient pathways built on artificial intelligence-augmented measures of antimicrobial treatment imprecision.

Posaconazole: the case for therapeutic drug monitoring.

Invasive fungal infections are associated with high morbidity and mortality. Antifungal therapeutic options remain relatively limited; therefore, optimization of present regimens is essential. Posaconazole is licensed for prevention of invasive fungal infections and oropharyngeal candidiasis and salvage therapy for invasive aspergillosis. Recent data suggest that therapeutic drug monitoring may be an important tool for patient management. Clinical and laboratory animal data suggest that posaconazole demonstrates clinically relevant exposure-response relationships. Higher systemic drug exposure is associated with improved clinical outcomes. Potentially subtherapeutic concentrations are frequently encountered in critically ill patients. Therapeutic drug monitoring provides a way to optimize the use of posaconazole, and this review summarizes the indications and process by which this can be achieved.

Use of stent grafts in lower extremity trauma.

BACKGROUND: Permanent endovascular stenting is gradually becoming recognized as a safe and efficacious method for treating a variety of arterial diseases. The literature on its application in trauma care is sparse, although indications for usage continue to evolve. METHODS: We retrospectively reviewed all penetrating extremity trauma treated with endovascular therapy at our medical center between 2005 and 2008. RESULTS: We present three patients with three different arterial lesions in the superficial femoral artery (SFA) which were caused by penetrating injury. The arterial lesions include a mid-thigh SFA pseudoaneurysm, an intimal disruption of the distal SFA, and an arteriovenous fistula involving the SFA and superficial femoral vein. All were treated with expanded polytetrafluoroethylene-covered stents and showed excellent short-term results. A percutaneous approach to this problem may reduce blood loss, decrease length of stay, involve fewer iatrogenic nerve injuries, and facilitate shorter recovery time, as compared with open approaches. CONCLUSIONS: Endovascular-covered stent placement for traumatic arterial extremity injury was used with excellent results and no morbidity in this small series of patients. Endovascular solutions for arterial extremity injuries warrant further investigation for short- and long-term results.

Decreasing Incisional Hernia by Teaching 4:1 Suture to Wound Length Ratio Early in Surgical Education.

OBJECTIVE: Incisional hernia formation has become a major burden for our healthcare system. One factor that has been shown to reduce incisional hernia rates that can be impacted on by the surgeon is the ability to achieve a 4:1 suture to wound length ratio. The purpose of this study is to evaluate whether a focused educational program for surgical residents can help improve laparotomy closures and be successful in achieving 4:1 suture to wound length ratios. DESIGN: Following Institutional Review Board approval, consecutive abdominal wall closures were reviewed from December 2013 to July 2016. S:W length ratios were calculated in all cases and after 100 cases a formal audit of success and risk factors for not achieving a 4:1 ratio was performed followed by a formal resident education on laparotomy closure. The ability to achieve a 4:1 ratio for the first 100 cases following resident education was then compared to the 100 patients preceding the education with a p-value of <0.05 considered significant. RESULTS: Two hundred patients underwent midline laparotomy with S:W length ratio calculated. In the first 100 patients, 76% of patients received a 4:1 S:W closure. Following resident education, this improved to 90% in the second 100 patients (p = 0.0083). Among patients where 2 residents performed the abdominal closure, 50% got an adequate 4:1 closure. This improved to 92% for the second 100 patients (p = 0.016). CONCLUSION: A 4:1 S:W length ratio is a simple technique that has been proven to decrease incisional hernia. It requires no additional cost and can easily be implemented into practice. The act of formal resident education and measuring suture tails to calculate a S:W ratio on each case holds surgeons accountable and improves success rate of achieving a 4:1 ratio.

Comparing quality-of-life outcomes in symptomatic patients undergoing laparoscopic or open ventral hernia repair.

BACKGROUND: The aim of this study was to compare quality-of-life outcomes in patients with symptomatic hernias who were undergoing laparoscopic and open repairs. MATERIALS AND METHODS: Clinical data for patients undergoing ventral hernia repair were reviewed with quality-of-life surveys administered before and at least 6 months following surgery. RESULTS: The study included 56 symptomatic patients. Forty-one patients (73%) underwent laparoscopic repair, and 15 patients (27%) underwent open repair. There was no difference in preoperative quality-of-life scores on the SF-36 Health Survey between patients having laparoscopic or open repairs. Postoperative quality-of-life scores on the SF-36 survey were significantly improved in the laparoscopic group, compared with the open group, in general health (46% vs. 37%; P=0.0217), vitality (53% vs. 45%; P=0.0491), role-emotional (45% vs. 35%; P=0.0480), and mental health (49% vs. 39%; P=0.0381). Postoperative quality-of-life scores on the Carolinas Comfort Scale (CCS) were significantly improved in the laparoscopic group, compared with the open group, in bending over (3.15 vs. 5.87, P=0.0158), sitting up (2.51 vs. 5.13; P=0.0211), activities of daily living (2.48 vs. 5.75; P=0.0139), coughing or deep breathing (2.95 vs. 5.75; P=0.0314), walking (2.36 vs. 4.62; P=0.0427), exercising (3.19 vs. 6.14; P=0.0222), and total comfort scale (17.62 vs. 40.23; P=0.0084). CONCLUSIONS: Laparoscopic ventral hernia repair provides improved quality-of-life, compared with open repair, 6 months postoperatively. Nearly all physical variables measured by the CCS were significantly better when ventral hernias were repaired laparoscopically.

Prophylactic Mesh for Hernia Prevention: Has the Time Arrived?

Incisional and parastomal hernias continue to be vexing problems for patients and surgeons. Risk factors are generally patient-related and/or technical in nature, and in some cases, can be altered, resulting in improved outcomes. Improved fascial closure techniques can only partly reduce the risk of incisional hernia formation. Even under optimal circumstances, using time tested closure techniques and materials, the rate remains high, due primarily to factors that are not modifiable or are unidentifiable. In such cases, there may be a beneficial role for prophylactic mesh augmentation (PMA), wherein mesh is implanted at the time of initial surgery or stoma formation. Several high-risk groups that might benefit from PMA have been identified, including patients undergoing open abdominal aneurysm repair or colorectal procedures, obese patients, and patients requiring creation of permanent gastrointestinal or urological stomas. Although the initial results of PMA are promising, the benefits of this strategy must be weighed against potential risks. Outcome measures to assess efficacy should include not only hernia recurrence but also quality of life, surgical-site occurrences, and cost. Further studies are warranted to predict which specific patient populations might benefit most from PMA and to identify ideal mesh materials as well as preferred implantation sites and methods of mesh fixation.

Role of Prophylactic Mesh Placement for Laparotomy and Stoma Creation.

Incisional and parastomal hernias are a cause of significant morbidity and have a substantial effect on quality of life and economic costs for patients and hospital systems. Although many aspects of abdominal hernias are understood, prevention is a feature that is still being realized. This article reviews the current literature and determines the utility of prophylactic mesh placement in prevention of incisional and parastomal hernias.

Atypical hernias: suprapubic, subxiphoid, and flank.

Thorough knowledge of anatomy, appropriate preoperative planning, and reliance on the principles of hernia repair ensure successful outcomes. There are many options for repair, including technique and mesh choice. The hernia surgeon should be well versed in the open and laparoscopic approaches and apply them based on the individual clinical presentation. Long-term outcomes related to suprapubic, subxiphoid, and lateral hernia repairs are limited; however, open and laparoscopic repairs using wide mesh overlap and adequate fixation have acceptable outcomes and recurrence rates. Future research will likely focus on comparative studies based on patient factors, techniques, mesh, and cost.

Evaluation of the pharmacokinetics and clinical utility of isavuconazole for treatment of invasive fungal infections.

INTRODUCTION: Invasive fungal infections remain a leading cause of infectious morbidity and mortality in immunocompromised patients. There are relatively few effective antifungal agents, and currently available agents all have significant limitations. Isavuconazole is a novel second-generation triazole with broad-spectrum antifungal activity, and a favorable pharmacokinetic-pharmacodynamic profile. Isavuconazole is available as an oral and intravenous formulation. Phase III studies that are examining the efficacy of isavuconazole for invasive candidiasis and invasive aspergillosis are currently in progress. AREAS COVERED: This review provides a summary of the pharmacological characteristics of isavuconazole and the potential future use of this agent. The preclinical and clinical pharmacokinetics and pharmacodynamics are discussed. This review was constructed by searching isavuconazole, triazole, pharmacokinetics and pharmacodynamics in PubMed. References and abstracts that were not identified by this method were retrieved from the respective publications. EXPERT OPINION: Isavuconazole has the potential to become an important agent for the treatment of invasive fungal infections, principally because of its relatively broad and potent in vitro antifungal activity, and its favorable pharmacokinetic profile. Further preclinical and clinical studies are required to define the clinical utility of this agent, especially for invasive candidiasis and invasive aspergillosis. Further information is required on the likely drug interactions, and in vitro susceptibility breakpoints for medically important invasive fungal pathogens. Further pharmacokinetic studies are also required in a range of patient populations to quantify the extent and sources of pharmacokinetic variability.

The management of Candida infections in preterm neonates and the role of micafungin.

The burden of neonatal invasive Candida infection (ICI) has been increasing recently and identification of effective preventative and treatment strategies is a priority. In this view, the echinocandin class of antifungal agents has emerged as a suitable and promising option for treatment. These agents have overall characteristics that suitably meet the needs of neonatal patients, such as coverage against biofilms and against fluconazole-resistant strains of Candida spp, which is an issue in an epoch of increasing prophylactic use of fluconazole in the nursery. Micafungin is the only echinocandin authorized for neonatal use by the EMA, based on efficacy and PK data from neonatal populations. Although the kinetics and appropriate dosing of this agent in premature and term infants have been described in the recent years, through either neonatal studies or extrapolation form adult data, further studies are needed to better address this area. These studies should be properly designed for neonatal populations, and must better address long-term safety and the clinical outcomes related to echinocandin use in neonates.