Current treatment strategies for infection of chronic wounds often result in compromised healing and necrosis due to antibiotic toxicity, and underlying biomarkers affected by treatments are not fully known. Here, a multifunctional dressing was developed leveraging the unique wound-healing properties of chitosan, a natural polysaccharide known for its numerous benefits in wound care. The dressing consists of an oxygenating perfluorocarbon functionalized methacrylic chitosan (MACF) hydrogel incorporated with antibacterial polyhexamethylene biguanide (PHMB). A non-healing diabetic infected wound model with emerging metabolomics tools was used to explore the anti-infective and wound healing properties of the resultant multifunctional dressing. Direct bacterial bioburden assessment demonstrated superior antibacterial properties of hydrogels over a commercial dressing. However, wound tissue quality analyses confirmed that sustained PHMB for 21 days resulted in tissue necrosis and disturbed healing. Therefore, a follow-up comparative study investigated the best treatment course for antiseptic application ranging from 7 to 21 days, followed by the oxygenating chitosan-based MACF treatment for the remainder of the 21 days. Bacterial counts, tissue assessments, and lipidomics studies showed that 14 days of application of MACF-PHMB dressings followed by 7 days of MACF dressings provides a promising treatment for managing infected non-healing diabetic skin ulcers.

Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is increasingly used for a diverse range of wounds. Meanwhile, the topical wound irrigation solution consisting of polyhexamethylene biguanide and betaine (PHMB-B) has shown efficacy in managing wound infections. However, the effectiveness of this solution as a topical instillation solution for NPWTi-d in patients with diabetic foot infections (DFIs) has not been thoroughly studied. The objective of this retrospective study was to evaluate the impact of using PHMB-B as the instillation solution during NPWTi-d on reducing bioburden and improving clinical outcomes in patients with DFIs. Between January 2017 and December 2022, a series of patients with DFIs received treatment with NPWTi-d, using either PHMB-B or normal saline as the instillation solution. Data collected retrospectively included demographic information, baseline wound characteristics, and treatment outcomes. The study included 61 patients in the PHMB-B group and 73 patients in the normal saline group, all diagnosed with DFIs. In comparison to patients treated with normal saline, patients with PHMB-B exhibited no significant differences in terms of wound bed preparation time (P = 0.5034), length of hospital stay (P = 0.6783), NPWTi-d application times (P = 0.1458), duration of systematic antimicrobial administration (P = 0.3567), or overall cost of hospitalization (P = 0.6713). The findings of the study suggest that the use of either PHMB-B or normal saline as an instillation solution in NPWTi-d for DFIs shows promise and effectiveness, yet no clinical distinction was observed between the two solutions.

OBJECTIVE: To report first clinical use of novel medical treatment for Acanthamoeba keratitis.
METHODS: Interventional observational case series. Two patients with Acanthamoeba keratitis were unsuccessfully treated with polihexanide (PHMB) 0.02% and propamidine 0.1% for 6 weeks, then all were shifted in a compassionate use of PHMB 0.08% with novel standardized protocol. The postinterventional follow-up of patients was at least 7 months.
RESULTS: PHMB 0.08% eyedrops in a novel standardized protocol improved infection resolution and led to complete healing of the lesion after 4 weeks in the two cases. Corneal opacities and neovascularization decreased slowly, best-corrected visual acuity slightly improved and progressively increased in the further 7 months, and no infection recurrence occurred.
CONCLUSIONS: This preliminary report of two cases shows promising response to polihexanide 0.08% lowering drastically the illness duration, with reduced chance of recurrence, and mostly improving patients\' quality of life.

BACKGROUND: Historically, bladder washouts were used to instil therapeutic reagents directly into the bladder. This practice has expanded to include instillation of solutions that deal with catheter issues such as encrustation or formation of bio-film. They appear to provide a promising strategy for people with long term catheters. These products are readily available to purchase, but there is concern that people are using these solutions without a complete understanding of the purpose for the rinse and without clinical guidance to monitor response to treatment.
METHODS: These case studies include three people living with spinal cord injury (SCI) who developed severe autonomic dysreflexia (AD) when a catheter rinse was carried out using a particular solution. Each of the cases developed immediate and, in some cases, intractable AD requiring further intervention to resolve symptoms.
CONCLUSIONS: Catheter-associated urinary tract infection is a significant cause of morbidity and mortality in people living with SCI. Long-term catheters provide a vector for opportunistic micro-organisms to form bio-film and create an environment that promotes formation of struvite calculi, thus increasing the risk of chronic catheter blockage and urinary tract infection. Whilst these solutions are used to reduce these risks, they also pose additional risks to people susceptible to AD. These cases highlight the need for judicious patient selection and clinical oversight and management of adverse events when using catheter rinse solutions in certain people living with SCI. This is supported by a decision-making algorithm and a response to AD algorithm. This case report was prepared following the CARE Guidelines (supplementary file 1).

This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical features, diagnosis, medical and surgical therapy, as well as outcomes of Acanthamoeba keratitis (AK). AK is a significant cause of ocular morbidity, and early diagnosis with timely institution of appropriate therapy is the key to obtaining good outcomes. The varied presentations result in frequent misdiagnosis, and co-infections can increase the morbidity of the disease. The first line of therapy continues to be biguanides and diamidines, with surgery as a last resort.

UNASSIGNED: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking.
UNASSIGNED: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution.
UNASSIGNED: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis.
UNASSIGNED: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure.
UNASSIGNED: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition.
UNASSIGNED: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups.
UNASSIGNED: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting.
UNASSIGNED: drks.de Identifier: DRKS00012251.

Women have a high risk of frailty independently of age and menopause state. Diabetes and hypertension increase the risk of frailty and cognitive impairment. Metformin has been employed in post-menopausal women and some reports have shown encouraging effects in terms of attenuated frailty. However, the impact on cognitive performance of a recently introduced extended-release formulation of metformin has never been explored.
We studied consecutive frail hypertensive and diabetic older women presenting at the ASL (local health authority of the Italian Ministry of Health) Avellino, Italy, from June 2021 to August 2022, who were treated or not with extended-release metformin. We included a control group of frail older males with diabetes and hypertension treated with extended-release metformin and a control group of frail older women with diabetes and hypertension treated with regular metformin.
A total of 145 patients successfully completed the study. At the end of the 6-month follow-up, we observed a significantly different cognitive performance compared to baseline in the group of frail women treated with extended-release metformin (p: 0.007). Then, we compared the follow-up groups and we observed significant differences between frail women treated vs. untreated (p: 0.041), between treated frail women and treated frail men (p: 0.016), and between women treated with extended-release metformin vs. women treated with regular metformin (p: 0.048). We confirmed the crucial role of extended-release metformin applying a multivariable logistic analysis to adjust for potential confounders.
We evidenced, for the first time to the best of our knowledge, the favorable effects on cognitive impairment of extended-release metformin in frail women with diabetes and hypertension.

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides.

Biguanides may cause lactic acidosis (LA) in elderly patients. We report three cases of LA after the administration of biguanides. Case 1 was an 85-year-old man with no hepatic dysfunction who was discharged, case 2 was a 67-year-old man with no hepatic dysfunction who was discharged, and case 3 was a 77-year-old woman with hepatic dysfunction who died. Therefore, caution should be exercised in administering biguanides to elderly patients with hepatic dysfunction.