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Objective: To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). Method: This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. Results: A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7–90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. Conclusion: In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. Declaration of interest: This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare. [ABSTRACT FROM AUTHOR]

The Park‐Bench Position (PBP) is associated with a high incidence rate of intraoperatively acquired pressure injuries (IAPIs). Preventive measures must be established to prevent the development of IAPIs. We investigated the risk factors for PBP by applying a soft silicone multilayered foam dressing (SMD) under core temperature management to prevent IAPIs. We conducted a prospective, single‐centre, open‐label observational study of patients undergoing elective neurosurgery operations using PBP in a university hospital in Japan. The incidence rate of IAPIs in this study was compared with that in our two previous studies, in which a film dressing was applied and core temperature management was not performed. IAPIs developed in 90 patients (6.7%); in the lateral thoracic region in five patients and the iliac crest region in one patient. The operative time (every 1 h: p = 0.0001, OR: odds ratio 3.62, 95% CI: confidence interval 1.73–11.42) was significantly associated with the incidence of IAPIs. In our two previous studies, the incidence rate of IAPIs was 11.0% and 24.1%, respectively, when film dressing was used. SMD may weaken the involvement of risk factors in IAPIs. [ABSTRACT FROM AUTHOR]

Objective: Intra-soft tissue and intramedullary antibiotic perfusion (iSAP and iMAP), which combine continuous administration of antibiotic solution to the wound and negative pressure wound therapy (NPWT), have been reported to be a useful management approach for hard-to-heal ulcers in the field of orthopaedic surgery. We report the efficacy of this treatment and discuss the key points. Method: The recipients of this treatment had contaminated fresh severe trauma with a high risk of infection, or hard-to-heal ulcers which were expected to be difficult to manage with conventional NPWT alone. Continuous administration of 1200µg/ml of gentamicin (GM) solution to the wound was performed along with NPWT. The GM solution was administered subcutaneously using a small catheter for iSAP, while intramedullary administration used a bone marrow needle for iMAP. Results: iSAP was employed in all 10 patients who took part, and iMAP in three of these patients. The average treatment time was 13.6 days with iSAP and 9.3 days with iMAP. The mean serum GM level during the therapy was 1.02µg/ml. Moderate GM-induced acute kidney injury was suspected in one case, but resolved spontaneously after GM administration was stopped. Favourable wound bed preparation was achieved in all cases without recurrence of infection. Conclusion: Combination with continuous suction by NPWT is able to keep the local concentration of antibiotic above the minimum inhibitory concentration of biofilm-coated bacteria within the wound. We have referred to this treatment as continuous local antibiotic perfusion. Further investigation of local pharmacodynamics in the wound and side-effects of this treatment are warranted. [ABSTRACT FROM AUTHOR]

Local low‐frequency vibration promotes blood flow and wound healing in hard‐to‐heal diabetic foot ulcers (DFUs). However, vibration treatment is challenging in patients with DFUs due to wound management difficulties and low adherence. Consequently, developing wearable self‐care devices becomes imperative for effective wound healing. This study introduces a wearable vibration dressing and assesses its impact on wound healing in hyperglycemic rats. Low‐frequency vibration at 52 Hz was applied to the wound for 40 min/day in awake rats. Relative wound areas on post‐wounding days (PWDs) 4–7 were significantly smaller and the wound closure rate was significantly higher in the vibration group than in the control group (p < 0.05, respectively). The total haemoglobin at baseline and after vibration on post‐wounding day 7 was significantly larger in the vibration group than in the control group (p < 0.05). On PWD 7, the thickness of the granulation tissue was significantly higher in the vibration group than in the control group (p < 0.05). Moreover, the number of blood vessels at the wound site and vascular endothelial growth factor A protein expression were significantly higher in the vibration group than in the control group (p < 0.05, respectively). The ratio of (CD68+/iNOS+)/(CD163+) macrophages in the vibration group was significantly lower than that in the control group (p < 0.05). These results indicate the potential of wearable vibration dressings as new self‐care devices that can promote angiogenesis and blood flow, improve inflammation, and enhance wound healing in DFUs. [ABSTRACT FROM AUTHOR]

Objective: We previously reported that dickkopf WNT signaling inhibitor 3 (DKK3) would modulate malignant potential of oral squamous cell carcinoma (OSCC) via activating Akt. Recently, cytoskeleton associated protein 4 (CKAP4) functions as receptor of DKK3, which activates Akt in esophageal squamous cell carcinoma, but its expression and function in OSCC were unclear. Methods: We studied DKK3 and CKAP4 protein expression in OSCC tissue and investigated the correlation between protein expression and clinical data. We also investigated whether antibodies (Ab) for DKK3 or CKAP4 could suppress malignant potential of the cancer cells. Results: DKK3/CKAP4 protein expression was observed in majority of OSCC cases and was associated with significantly higher T‐stage and TNM stage. Multivariate analysis revealed that DKK3 and CKAP4 were independent prognostic biomarkers for overall survival (OS) and disease‐free survival (DFS), respectively. Survival analyses revealed that DKK3‐positive cases and CKAP4‐positive cases showed significantly shorter OS and DFS, respectively, and that DKK3/CKAP4 double‐negative cases showed significantly favorable prognosis. Both anti‐DKK3Ab and anti‐CKAP4Ab could suppress cancer cell proliferation, migration, and invasion. Conclusion: DKK3/CKAP4 axis is thought to be important in OSCC, and it would be a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Purpose: The World Health Organization recommends prophylactic negative pressure wound therapy (NPWT) for high-risk SSI wounds, despite which delayed wound healing (DWH) remains a problem. The aim of this study was to define the risk factors for DWH under prophylactic NPWT following colorectal perforation (CP). Methods: The subjects of this retrospective study were patients who underwent emergency laparotomy and prophylactic NPWT for CP between 2011 and 2019 at Fujisawa City Hospital in Japan. Multivariable analysis was performed to identify which perioperative factors impact DWH. Results: A total of 58 patients met the inclusion criteria and the median period from surgery to wound closure was 12 days (IQR: 8–18). Most factors, including preoperative steroid use, diabetes, and serum albumin, were not associated with DWH, although patients requiring catecholamine were more likely to have DWH (OR 7.81, 95% CI 1.55–39.24, p = 0.013). The median in-hospital cost was more than double for patients with DWH vs. those without DWH (41.36 kUSD [IQR 24.95–51.89] vs. 20.32 kUSD [IQR 16.69–28.45], p < 0.001). Conclusion: Catecholamine use was a greater risk factor for DWH than previously reported factors such as diabetes and the serum albumin level. Further study is needed to investigate strategies to prevent DWH and optimize the utilization of NPWT, especially in patients requiring catecholamine. [ABSTRACT FROM AUTHOR]

The article offers information on scar care and patient satisfaction after surgery, specifically focusing on caesarean sections and breast cancer surgery. It discusses the challenges of achieving completely scar-less healing and the development of problematic scars. It mentions that the symposium aims to address the issues related to scar care and propose conventional dressing methods for reducing the development of problematic scars.

Simple Summary: Extrahepatic cholangiocarcinoma (EHCC) is an aggressive tumor. The five-year survival rate for patients who undergo surgical resection is only 20–40% due to recurrences. Therefore, elucidating the molecular mechanisms underlying invasion and metastasis in EHCC is crucial for developing adjuvant therapy. The epithelial–mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in two EHCC cell lines. CCR7 mediates cell invasion and migration in EHCC by inducing EMT, which was abrogated by a CCR7 antagonist. CCR7 may be a potential target for adjuvant therapy in EHCC. The epithelial–mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (EHCC) remains unknown. This study aimed to elucidate the prognostic impact of CCR7 expression and its association with clinicopathological features and EMT in EHCC. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in TFK-1 and EGI-1 EHCC cell lines. High-grade CCR7 expression was significantly associated with a large number of tumor buds, low E-cadherin expression, and poor overall survival. TFK-1 showed CCR7 expression, and Western blotting revealed E-cadherin downregulation and vimentin upregulation in response to CCL19 treatment. The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC. [ABSTRACT FROM AUTHOR]

A monitoring tool for the wound‐healing process of diabetic foot ulcers (DFUs) was developed. It comprises seven domains, namely, depth, maceration, inflammation/infection, size, tissue type of the wound bed, type of wound edge, and tunnelling/undermining. It was named "DMIST" based on the initials of its domains. Although DMIST is useful for assessing wound‐healing processes, the monitoring items related to wound healing remain unclear, thereby making the selection of optimal care based on the assessment difficult. We identified the relationship between the DMIST items and wound healing. This study was a secondary analysis of five previous investigations and was conducted using DMIST based on the diabetic foot ulcer assessment scale score and DFU images. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) after simultaneously controlling for potential confounders. The examined DFU healing status revealed that some DFUs healed at 4 weeks from baseline, whereas some DFUs did not. Variables considered in the models were the scores of each DMIST domain. The study population comprised 146 Indonesian patients and 33 Japanese patients. Depth, maceration, and size were associated with DFU healing at 4 weeks from baseline [depth: OR = 0.317 (95% CI: 0.145‐0.693, P = 0.004); maceration: OR = 0.445 (95% CI: 0.221‐0.896, P = 0.023); size: OR = 0.623 (95% CI: 0.451‐0.862, P = 0.004)]. Our findings suggest that appropriate management of maceration promotes DFU healing. [ABSTRACT FROM AUTHOR]

Objective: The Japanese Society of Pressure Ulcers (JSPU) has two purposes: first, to improve knowledge and skills among health professionals related to preventing and managing pressure ulcers (PUs); and second, to represent those in the field managing PUs, including with government and health authorities. Since 2006, JSPU has conducted fact-finding surveys about every four years to identify PU prevalence in Japan (2006, 2010, 2013 and 2016). Based on the prevalence identified by these surveys, an attempt was made to validate the achievements of JSPU's activities. Method: Information from one-day surveys of hospitals, long-term care health facilities, long-term care welfare facilities, and home visit nursing care stations was analysed. We used generalised estimating equations to estimate the proportions of PUs and their 95% confidence intervals (CIs) for each survey. Results: A total of 662,419 patients in 2631 facilities participated in the surveys. The estimated proportions for all facilities (95% CI) in chronological order, from the first to the fourth survey, were: 2.67% (2.52–2.83); 2.61% (2.43–2.80); 1.99% (1.83–2.17); and 1.79% (1.65–1.94), respectively. In all facility types, the proportion of PUs was lower in the fourth survey than the first survey. Conclusion: The proportion of PUs showed a decreasing trend and was low according to global standards, demonstrating the efficacy of JSPU's activities. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the impact of infrapopliteal (IP) revascularisation establishing in line flow to the wound (IFW) on wound healing in chronic limb threatening ischaemia (CLTI), using a core laboratory assessment for wounds and in line flow., Methods: The Wound directed Angiosome RevasculaRIsation apprOach to patients with cRitical limb iSchaemia (WARRIORS) multicentre observational study enrolled patients with CLTI with tissue loss undergoing IP revascularisation in Japan, with scheduled two year follow up. The primary outcome measure was complete wound healing, defined as achievement of complete epithelialisation of all wounds without major amputation. IP revascularisation establishing IFW was defined as revascularisation after which a tibiopedal artery that actually fed an injured pedal unit was patent. The incidence of wound healing was compared between the IFW and non-IFW groups using inverse probability of treatment weighting based on the propensity score., Results: A total of 440 patients with CLTI (median age, 75 years; male, 64.1%; diabetes mellitus, 72.0%; dialysis, 57.7%) with tissue loss (Wound, Ischaemia, and foot Infection stage 4, 66.4%) who underwent IP revascularisation (endovascular procedure, n = 304; bypass grafting, n = 136) between October 2017 and June 2020 were registered. During a median follow up of 23.6 months, 51.1% achieved wound healing. Successful IP revascularisation with IFW was achieved in 68.2%. After analysis, the IFW group had a higher rate of wound healing than the non-IFW group (34.5 vs. 16.1 per 100 person years; p = .030). The association between IFW and wound healing was not statistically different between patients undergoing bypass grafting and those undergoing an endovascular procedure (p for interaction = .38). There was no statistically significant interaction effect between IFW and direct revascularisation for wound healing (p for interaction = .51)., Conclusion: IP revascularisation establishing IFW was statistically significantly associated with a higher wound healing rate in patients with CLTI., (Copyright © 2024 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Pressure injury (PI) prevention is a huge industry and involves various interventions. Temperature and moisture are important factors for wound healing; however, the active mechanism by which "moist heat" affects PI prevention has not yet been clarified. Thus, we explored the protective and therapeutic effects of hydrotherapy on PI based on the preconditioning (PC) principle, which might be useful for clinical practice. This study aimed to investigate the preventive mechanisms of heat shock preconditioning on PIs in rat models. The experiment was performed in the basic medical laboratory of Nagano College of Nursing in Japan. Ten rats were divided into two groups, with five rats in each group. Rats in the control group were not bathed. Rats in the preconditioning group (PC group) were bathed with hot tap-water. Bathing was conducted thrice a week. After bathing for 4 weeks, the PI model was constructed on the rats' dorsal skin. The skin temperature, skin moisture, and area of ulcers were compared between the two groups. In vitro, we investigated the expression of heat shock protein 27 (Hsp27) in 6, 12, and 24 h after the PI model was constructed through Western blot analysis. Ulcers occurred in the control group 24 h after the PI model constructed, wheras the PC group exhibited ulcers after 36 h. The ulcer area was larger in the control group than that in the PC group after 24 h (all p < 0.05). The temperatures of PI wounds in the control group decreased and were lower than those in the PC group after 1, 6, 12, 36, and 48 h (all p < 0.05). However, the skin moisture levels of PI wounds increased in the control group and were higher than those in the PC group at the same time (all p < 0.05). Using Western blot analysis, hydrotherapy preconditioning showed the potential to increase Hsp27 expression after pressure was released (p < 0.05). We determine that heat shock preconditioning had a preventive effect on PIs in rat models, a result that may be associated with their actions in the upregulation of Hsp27. [ABSTRACT FROM AUTHOR]

Objective: Diabetic foot ulcer (DFU) is recognised as a severe complication in patients with type 2 diabetes. With the increasing incidence of diabetes, it represents a major medical challenge. Several models have been proposed to explain its aetiology; however, they have never been assessed by longitudinal histopathological examination, which this study aims to address. Method: Multiplex-immunofluorescence analysis was carried out with lengthwise serial skin specimens obtained from the medial thigh, lower leg, ankle, dorsum of foot and acrotarsium close to the DFU region of a patient with type 2 diabetes receiving above the knee amputation. Results: Proximal-to-distal gradual loss of peripheral nerve was demonstrated, accompanied by compromised capillaries in the superficial papillary plexus and distended CD31-positive capillaries in the dorsum of foot. Neural fibres and capillaries were also significantly compromised in the sweat gland acinus in the ankle and dorsum of foot. Injuries in the superficial papillary plexus, sweat gland acinus, and sweat gland-associated adipose tissues were accompanied by significant infiltration of macrophages. These results indicated that longitudinal impairment of local blood circulation could be the cause of peripheral neuropathy, which initiated ulcer formation. Resultant chronic inflammation, involving sweat gland-associated adipose tissue, gave rise to impairment of wound healing, and thus DFU formation. Conclusion: Longitudinal histopathological examination demonstrated that impairment of local microvascular circulation (rather than the systemic complication caused by type 2 diabetes) was considered the primary cause of peripheral neuropathy, which initiated ulceration. Together with chronic inflammation in the superficial papillary plexus and sweat gland-associated adipose tissue, it resulted in the development of a DFU. Although this is a study of just one individual's limb, our study provided a unique observation, contributing mechanistic insights into developing novel intervening strategies to prevent and treat DFUs. [ABSTRACT FROM AUTHOR]

Background: Wnt/β-catenin signaling suppresses the differentiation of cultured tenocytes, but its roles in tendon repair remain mostly elusive. No chemical compounds are currently available to treat tendon injury. Hypothesis: We hypothesized that the inhibition of Wnt/β-catenin signaling would accelerate tendon healing. Study Design: Controlled laboratory study. Methods: Tendon-derived cells (TDCs) were isolated from rat Achilles tendons. The right Achilles tendon was injured via a dermal punch, while the left tendon was sham operated. A Wnt/β-catenin inhibitor, IWR-1, and an antihistamine agent, promethazine (PH), were locally and intramuscularly injected, respectively, for 2 weeks after surgery. The healing tendons were histologically and biomechanically evaluated. Results: The amount of β-catenin protein was increased in the injured tendons from postoperative weeks 0.5 to 2. Inhibition of Wnt/β-catenin signaling by IWR-1 in healing tendons improved the histological abnormalities and decreased β-catenin, but it compromised the biomechanical properties. As we previously reported that antihistamine agents suppressed Wnt/β-catenin signaling in human chondrosarcoma cells, we examined the effects of antihistamines on TDCs. We found that a first-generation antihistamine agent, PH, increased the expression of the tendon marker genes Mkx and Tnmd in TDCs. Intramuscular injection of PH did not improve histological abnormalities, but it decreased β-catenin in healing tendons and increased the peak force and stiffness of the healing tendons on postoperative week 2. On postoperative week 8, however, the biomechanical properties of vehicle-treated tendons became similar to those of PH-treated tendons. Conclusion: IWR-1 and PH suppressed Wnt/β-catenin signaling and improved the histological abnormalities of healing tendons. IWR-1, however, compromised the biomechanical properties of healing tendons, whereas PH improved them. Clinical Relevance: PH is a candidate repositioned drug that potentially accelerates tendon repair. [ABSTRACT FROM AUTHOR]

Background: Although various reconstruction techniques are available for anterior cruciate ligament (ACL) injuries, a long recovery time is required before patients return to sports activities, as the reconstructed ACL requires time to regain strength. To date, several studies have reported use of mesenchymal stem cells in orthopaedic surgery; however, no studies have used adipose-derived stem cell (ADSC) sheets in ACL reconstruction (ACLR). Hypothesis: ADSC sheet transplantation can improve biomechanical strength of the autograft used in ACLR. Study Design: Controlled laboratory study. Methods: A total of 68 healthy Japanese white rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into a control group (no sheet; n = 34) and a sheet group (ADSC sheet; n = 34). At 2, 4, 8, 16, and 24 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing using histological staining, micro–computed tomography, and biomechanical testing. At 24 weeks, scanning transmission electron microscopy of the graft midsubstance was performed. Results: The ultimate failure load for the control and sheet groups, respectively, was as follows: 17.2 ± 5.5 versus 37.3 ± 10.3 (P =.01) at 2 weeks, 28.6 ± 1.9 versus 47.4 ± 10.4 (P =.003) at 4 weeks, 53.0 ± 14.3 versus 48.1 ± 9.3 (P =.59) at 8 weeks, 66.2 ± 9.3 versus 95.2 ± 43.1 (P =.24) at 16 weeks, and 66.7 ± 27.3 versus 85.3 ± 29.5 (P =.39) at 24 weeks. The histological score was also significantly higher in the sheet group compared with the control group at early stages up to 8 weeks. On micro–computed tomography, relative to the control group, the bone tunnel area was significantly narrower in the sheet group at 4 weeks, and the bone volume/tissue volume of the tendon-bone interface was significantly greater at 24 weeks. Scanning transmission electron microscopy at 24 weeks indicated that the mean collagen fiber diameter in the midsubstance was significantly greater, as was the occupation ratio of collagen fibers per field of view, in the sheet group. Conclusion: ADSC sheets improved biomechanical strength, prevented bone tunnel enlargement, and promoted tendon-bone interface healing and graft midsubstance healing in an in vivo rabbit model. Clinical Relevance: ADSC sheets may be useful for early tendon-bone healing and graft maturation in ACLR. [ABSTRACT FROM AUTHOR]

In consultation with academia and the Pharmaceuticals and Medical Devices Agency (PMDA), we have developed guidance for drafting protocols for clinical trials concerning medical devices for the healing of hard-to-heal wounds without ischaemia. The guidance summarises the validity of single-arm trials for hard-to-heal wounds, the definition of hard-to-heal wounds without ischaemia, methods of patient enrolment and clinical endpoints. This review focuses on the logical thinking process that was used when establishing the guidance for improving the efficiency of clinical trials concerning medical devices for hard-to-heal wounds. We particularly focused on the feasibility of conducting single-arm trials and also tried to clarify the definition of hard-to-heal wounds. If the feasibility of randomised control trials is low, conducting single-arm trials should be considered for the benefit of patients. In addition, hard-to-heal wounds were defined as meeting the following two conditions: wounds with a wound area reduction <50% at four weeks despite appropriate standards of care; and wounds which cannot be closed by a relatively simple procedure (for example, suture, skin graft and small flaps). Medical devices for hard-to-heal wound healing are classified into two types: (1) devices for promoting re-epithelialisation; and (2) devices for improving the wound bed. For medical devices for promoting re-epithelialisation, we suggest setting complete wound closure, percent wound area reduction or distance moved by the wound edge as the primary endpoint in single-arm trials for hard-to-heal wounds. For medical devices for improving the wound bed, we suggest setting the period in which wounds can be closed by secondary intention or a simple procedure, such as the primary endpoint. Declaration of interest: The authors have no conflicts of interest directly relevant to the content of this article. The authors' views expressed in the present article do not necessarily reflect the official views of the Pharmaceuticals and Medical Devices Agency. [ABSTRACT FROM AUTHOR]

Objective: The use of 2-octyl cyanoacrylate with polyester mesh (OCA-M) has become common in total hip and knee arthroplasty (THA, TKA). We aimed to compare the safety and cosmetic outcomes between OCA-M and standard suture techniques and staples, and determine whether OCA-M can safely be used for TKA. Method: Inclusion criteria were patients who underwent THA or TKA from January 2010 to October 2011 (Suture group), November 2011 to August 2013 (Staple group), March 2017 to September 2018 (OCA-M group). Exclusion criteria was loss of imaging data. Complications during hospitalisation (early complication) and after discharge (late complication) were compared in groups. Plastic and orthopaedic surgeons performed cosmetic evaluations with the modified Vancouver Scar Scale (VSS) and Likert scale at three and six months postoperatively and compared in groups. Results: A total of 249 arthroplasties (suture group=88 patients; staple group=94 patients; OCA-M group=67 patients) were included in the study. The OCA-M group had a significantly lower early complication rate than the suture group (p=0.015). For THA, the OCA-M group had a significantly lower total complication rate than the suture group (p=0.048). For TKA, there was no significant difference among the three groups. The complication rate in the OCA-M group showed no significant difference between THA/TKA. With regards to the VSS, the OCA-M group was significantly better for cosmetic qualities than the suture group (p=<0.001, p=0.021 at three and six months, respectively). For the Likert scale, the OCA-M group was also significantly better for cosmetic qualities than the suture group and staple group (suture–OCA-M, p=0.003 (three months), p=<0.001 (six months); staple–OCA-M, p=0.027 (three months)). Conclusion: In this study, the OCA-M complication rate was low compared to suturing and similar to stapling. Moreover, better cosmetic outcomes were achieved compared to suturing and stapling. [ABSTRACT FROM AUTHOR]

Purpose: To assess skin perfusion pressure (SPP) changes after endovascular treatment (EVT) of patients with chronic limb-threatening ischemia (CLTI) and to explore preoperative factors that affect SPP changes.Materials and Methods: This prospective, multicenter study recruited 147 patients (mean age 74 years; 99 men) with ischemic wounds at 6 vascular centers in Japan between July 2017 and December 2018. Over half of the patients (92, 63%) were diabetic, and 76 (52%) required dialysis. Sixty-four patients (43%) had WIfI (wound, ischemia, foot infection) wound grades of 2 or 3; 59 (40%) had foot infections. SPP was measured before and 1, 2, 7, and 30 days after EVT to establish inline flow to the ischemic foot based on the angiosome concept when feasible. The anterior and posterior tibial arteries and the peroneal artery were revascularized in 66 (45%), 50 (34%), and 30 (21%) patients, respectively.Results: Both the dorsal and plantar SPPs at 1 or 2 days post-EVT were significantly higher than those at baseline (p<0.001), and both SPPs increased further at 1 month compared with those at 1 (p=0.001) or 2 days (p=0.006) post-EVT. SPP increases occurred on the dorsal and plantar surfaces of the foot regardless of the vessel revascularized. The SPP increase at 1 month after EVT was significantly lower in patients with foot infections than that in those without foot infections (p=0.003). Age, sex, diabetes, dialysis, wound severity, and direct revascularization did not affect the pattern of SPP change.Conclusion: The SPP increased continuously up to 1 month after EVT, though the increase was smaller in patients with wound infections. The SPP on the dorsal and plantar surfaces increased, regardless of the vessel revascularized, which could justify indirect revascularization when direct revascularization is technically challenging. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) comprises two major subtypes, ulcerative colitis (UC) and Crohn's disease, which are multifactorial diseases that may develop due to genetic susceptibility, dysbiosis, or environmental factors. Environmental triggers of IBD include food-borne factors, and a previous nationwide survey in Japan identified pre-illness consumption of isoflavones as a risk factor for UC. However, the precise mechanisms involved in the detrimental effects of isoflavones on the intestinal mucosa remain unclear. The present study employed human colonic organoids (hCOs) to investigate the functional effect of two representative isoflavones, genistein and daidzein, on human colonic epithelial cells. The addition of genistein to organoid reformation assays significantly decreased the number and size of reformed hCOs compared with control and daidzein treatment, indicating an inhibitory effect of genistein on colonic cell/progenitor cell function. Evaluation of the phosphorylation status of 49 different receptor tyrosine kinases showed that genistein selectively inhibited phosphorylation of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR). We established a two-dimensional wound-repair model using hCOs and showed that genistein significantly delayed the overall wound-repair response. Our results collectively show that genistein may exert its detrimental effects on the intestinal mucosa via negative regulation of stem/progenitor cell function, possibly leading to sustained mucosal injury and the development of UC. • Genistein inhibits organoid reformation and wound healing in human epithelial cells. • Genistein inhibits phosphorylation of HGFR and EGFR in human epithelial cells. • Genistein may contribute to the development and pathogenesis of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Objective: Unusual setting of medical care Background: Fingertip amputation injury is treated surgically or conservatively. Management strategies for these injuries vary depending on not only the site and the degree of tissue loss in the wound but also the country and region. Conservative management or revision amputation is common in the United States. On the other hand, operative management such as replantation or reconstruction is preferred in Japan; accordingly, a surgery is performed even in cases eligible for conservative management. Here, we report a case of fingertip amputation injury for which reconstructive surgery was recommended by a plastic surgeon, but the patient opted for conservative treatment, which was performed using moist wound dressings. Case Report: A 36-year-old woman suffered an Allen type III fingertip amputation injury with her right middle finger crushed in a thick iron door. The amputated fingertip was not retrieved. The plastic surgeon in charge initially recommended reconstructive surgery to the patient. However, the patient opted for conservative management; therefore, she visited the Wound Care Department in our hospital. Conservative treatment using moist wound dressings (Plus moist™) was performed, and the wound healed after 12 weeks, with outstanding aesthetic and functional results. Conclusions: Conservative management with moist wound dressings can be a successful treatment modality for Allen type III fingertip amputation injury. In cases where the fingertip amputation injury can be treated using either surgery or conservative treatment, it is better to prioritize the patient's wishes when selecting the treatment option. [ABSTRACT FROM AUTHOR]

Aim: To provide guidelines on the diagnosis, treatment, and prevention of skin ulcers in Werner syndrome. Methods: This article was based on literature from 1996, when WRN was identified as a gene responsible for Werner syndrome, and we evaluated several authentic clinical cases of genetically diagnosed patients. There were 63 patients with Werner syndrome in the Japanese reports retrieved from Medical Online between January 1996 and December 2017. There were 56 patients with Werner syndrome in English reports written by Japanese authors and retrieved from PubMed during the same period. Results: Records on skin ulcers were found in 27 (43%) out of 63 patients and 22 (40%) out of 56 patients from the Japanese and English reports, respectively. The reported ulcers were often located at the distal one‐third of the lower legs. There were 8 patients with callosities in the foot in the Japanese reports and 9 patients in the English reports. A skin ulcer in Werner syndrome is generally intractable. Weight‐bearing ulcers or callosity should be critically assessed in surgical procedures because they have effects on patient pain and gait. By adopting a recently advanced technique to facilitate wound healing, the cases of ulcers that were difficult to treat and those requiring major operations can be closed with minimally invasive surgery. Conclusions: Skin ulcers in Werner syndrome are refractory, and they lead to reduced quality of life of patients. A callosity in Werner syndrome is an important therapeutic target for the prevention of ulcers. Geriatr Gerontol Int 2021; 21: 153–159. [ABSTRACT FROM AUTHOR]

Objective: Early identification of pre-ulcerative pathology is important to preventing diabetic foot ulcers (DFU), but signs of inflammation are difficult to detect on the feet of patients with diabetic neuropathy due to decreased sensation. However, infrared thermography can objectively identify inflammation. Therefore, a device that allows patients to visualise thermograms of their feet might be an effective way to prevent DFU. We aimed to determine the effects of a novel self-monitoring device to prevent DFU using a thermograph attached to a smartphone. Method: A self-monitoring device comprising a mobile thermograph attached to a smartphone on a selfie stick was created, and its effects in two patients with diabetic neuropathy and foot calluses assessed. Results: For one patient, he understood that walking too much increased the temperature in the skin of his feet (a sign of inflammation). The other patient could not detect high-risk findings, because the temperature of his skin did not increase during the study period. Conclusion: This device might provide self-care incentives to prevent DFU, although some issues, such as the automatic detection of high-risk thermographic changes, need to be improved. [ABSTRACT FROM AUTHOR]

Objectives: The Japanese herbal medicine kyoseihatekigan (KHG) has been used to alleviate the symptoms of croaky voice and globus hystericus, and each of its components has anti-inflammatory and antioxidant effects. However, the mechanisms underlying these beneficial actions of KHG on the vocal folds remain largely unknown. We examined the effects of KHG on rat vocal fold wound healing and assessed its anti-inflammatory and antioxidant properties., Study Design: Animal model., Methods: The vocal folds of Sprague-Dawley rats were unilaterally injured under endoscopy. Rats were divided into three groups based on KHG dosing from pre injury day 4 to post injury day 3: 0 mg/kg/day (sham group), 500 mg/kg/day (1% KHG group) and 1000 mg/kg/day (2% KHG group). Histologic changes were examined to assess the degree of inflammation and oxidative stress at day 3, and fibrosis at day 56. In addition, gene expression related to pro-inflammatory cytokines and transforming growth factor-beta1 (TGF-β1) signaling was examined by quantitative real-time polymerase chain reaction (qPCR)., Results: Histologic analysis showed that the 1% and 2% KHG treatments significantly decreased cell infiltration and the 4-hydroxy-2-nonenalx-immunopositive area, and increased hyaluronic acid at day 3. Both KHG treatments significantly decreased fibrosis at day 56. qPCR revealed that mRNA of interleukin-1β and cyclooxygenase-2 were significantly suppressed at day 1 and TGF-β1 mRNA was significantly downregulated at day 5 in both KHG groups., Conclusions: The current findings suggest that KHG has anti-inflammatory and antioxidant effects in the early phase of vocal fold wound healing, which can lead to better wound healing with less scar formation., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To clarify the surgical indications and the appropriate perioperative management of ischial pressure ulcers (PUs). Method: A two-year prospective, nationwide registry study was carried out across 26 medical institutions in Japan. All participating institutions managed ischial PUs according to the standardisation of total management and surgical application for the refractory decubitus (STANDARDS-I) perioperative protocol. Analysis was conducted on a range of clinically or statistically important variables for the achievement of primary or secondary endpoints: complete wound healing and hospital discharge at three months, and complete wound healing at one month after surgery, respectively. Results: A total of 59 patients took part in the study. All patients underwent surgery for ischial PUs during the study period. Patients who had achieved the primary endpoint had a higer preoperative functional independence measurement (FIM score), a higher 'G' score in the DESIGN-R scale and were more likely to have healed by primary intention. Patients who had achieved the secondary endpoint were more likely to have spastic paralysis, preoperative physiotherapy and localised infection of the wound, among other variables. Conclusion: This survey suggests that preoperative physiotherapy increases the speed of wound healing, and good granulation of the wound bed preoperatively increases the likelihood of woundless discharge from hospital, whereas the existence of comorbidities negatively influences the likelihood of woundless discharge from hospital. The study also suggests that the existence of spastic paralysis, preoperative infection of the wound, or surgical reduction of the ischial tubercle speeds up the healing of the wound. However, the wound failed to heal significantly more often in patients with increasing white blood cell count after surgery. [ABSTRACT FROM AUTHOR]

Elental® is an L-glutamine-rich elemental diet (ED) that has been widely used in Japan as a nutritional supplement for malnourished patients. In addition, Elental® has been successfully used in the management of chemotherapy-induced mucositis in cancer patients. Recently, it was also reported that Elental® can effectively reduce chemotherapy-induced oral mucositis in patients with oral squamous cell carcinoma, and can also reduce mucositis and dermatitis in animal models. However, it is unclear whether oral intake or topical application of Elental® can act directly on chemotherapy-induced oral mucositis or dermatitis. The aim of the present study was to investigate the possible direct healing effect of Elental® on chemotherapy-induced dermatitis and raw wound areas in a mouse model. Dermatitis and raw wounds were induced in nude mice by administration of 5-fluorouracil (5-FU) (via gastric tube) and mechanical injury (using a metal brush or a surgical knife). We then compared the outcome following oral or topical application of Elental® in these mice. The effect of Elental® on the growth and migration ability of the human oral keratinocyte cell line, HOK, was also examined using MTT and migration assays, respectively. In the mouse model, both oral administration and topical application of Elental® reduced 5-FU-induced dermatitis and healed raw wound areas more effectively compared with the topical application of saline. The MTT assay revealed that Elental® exerted a growth-promoting effect on HOKs. In addition, Elental® enhanced the ability of HOKs to migrate, as demonstrated by the migration assay. These findings demonstrated that the topical application as well as the oral intake of Elental® exerted a direct healing effect on chemotherapy-induced dermatitis or raw wound areas. The data also indicated that oral intake of an ED may exert a direct healing effect on chemotherapy-induced oral mucositis. [ABSTRACT FROM AUTHOR]

Introduction: Basic fibroblast growth factor (bFGF) plays several key roles in wound healing. Over the last 2 decades, clinical and basic research on bFGF has been actively conducted in Japan with reports on its potent efficacy in accelerating the healing of chronic ulcers and burn wounds by stimulating key cellular players in the skin. However, its efficacy remains unrecognized internationally. Thus, this study reviews current knowledge about the therapeutic value of bFGF in wound management and scar prevention accumulated in Japan over the last 2 decades. Methods: We review the Japanese literature that demonstrates the anti-scarring effects of bFGF and exhaustively assess how these effects are exerted. Using the search terms "bFGF OR growth factors AND wound healing in Japan" and "bFGF AND scar prevention in Japan," we conducted a search of the PubMed database for publications on the role of bFGF in wound and scar management in Japan. All eligible papers published between 1988 and December 2019 were retrieved and reviewed. Results: Our search yielded 208 articles; 82 were related to the application of bFGF for dermal wound healing in Japan. Of these, 27 fulfilled all inclusion criteria; 11 were laboratory studies, 7 were case reports, 4 were clinical studies, and 5 were randomized controlled trials. Conclusion: Further research, with recognition of the therapeutic value of bFGF in wound and scar management and its clinical applications, is needed to provide additional clinical advantages while improving wound healing and reducing the risk of post-surgical scar formation. [ABSTRACT FROM AUTHOR]

A new diabetic foot evaluation scale was proposed, using the seven domains of depth, maceration, inflammation/infection, size, tissue type of the wound bed, type of wound edge, and tunneling/undermining. This scale was named "DMIST" as an acronym from the initials of the domains. The purpose of this study was to evaluate the validity of DMIST. Secondary analysis was conducted in three investigations performed using the diabetic foot ulcer assessment scale (DFUAS) in Japan and Indonesia. Secondary analysis was assessed using DMIST, PUSH, and DESIGN for 4 weeks based on DFUAS score and photographs of diabetic foot ulcers by researchers. Concurrent validity was determined from the correlation of total DMIST scores with PUSH and DESIGN scores. Construct validity was determined by comparisons between total DMIST score and grade of the Wagner classification. Predictive validity was determined by receiver operating characteristic curve analysis for wound non‐healing 4 weeks later. Subjects comprised 35 Japanese patients and 118 Indonesian patients. Correlations of total DMIST score with PUSH and DESIGN scores were 0.831 and 0.822, respectively. Comparison of total DMIST scores with grade of the Wagner classification (Grade I vs. Grade II/III vs. Grade IV/V) was p < 0.001. Based on an area under the curve of 0.872, a DMIST score of 9 was selected as a cut‐off, offering sensitivity of 0.855 and specificity of 0.786 for wound non‐healing 4 weeks later. Our findings suggest that DMIST offers high validity. [ABSTRACT FROM AUTHOR]

Treatment of pressure ulcers requires removing the cause as well as eliminating factors that interfere with healing. There are no reports on the effect of medications prescribed for underlying diseases on pressure ulcers. Accordingly, the aim of this study was to investigate whether medications prescribed to patients with pressure ulcers could be a factor that influences pressure ulcer healing. We retrospectively reviewed the records of patients with pressure ulcer who were admitted to Chiba University Hospital between June 2009 and June 2015. A total of 110 patients were included in this study. In univariate analysis, there were significant differences in corticosteroid use and total caloric intake. Logistic regression analysis was performed for four factors, including corticosteroid use and total caloric intake, which were significant at P <.05, plus the two factors malignancy and body mass index, which were previously reported as factors that may affect pressure ulcer healing. The results showed that corticosteroid use [odds ratio (OR) 0.205, 95% confidence interval (CI): 0.046 to 0.911, P =.037] and total caloric intake [OR 1.002, 95% CI: 1.000 to 1.003, P =.006] were significant risk factors influencing pressure ulcer healing. This study revealed that use of corticosteroids and total caloric intake could be risk factors affecting pressure ulcer healing. These findings provide useful information for the management of pressure ulcer. [ABSTRACT FROM AUTHOR]

Introduction: Fragility fractures can cause delayed wound healing after tooth extraction, which contributes to an increased risk of osteomyelitis of the jaw. We evaluated whether a history of fragility fracture was associated with increased risk of delayed wound healing after tooth extraction in older adults in Japan.Materials and Methods: Of 5352 people aged 50-89 years in the 2014 basic resident registry of the town of Obuse, the present study included 376 subjects (190 men and 186 women) who completed a structured questionnaire and measurement of the bone mineral densities (BMDs) of the bilateral femoral neck. Delayed wound healing after tooth extraction was self-reported. Fragility fractures were confirmed via examination of hospital medical records. Logistic regression analyses adjusted for age and gender were used to evaluate association of clinical variables with delayed would healing after tooth extractions. Odds ratios (ORs) and the 95% confidence intervals (CIs) of all possible associated variables for the presence of delayed wound healing were calculated.Results: Subjects with a history of fragility fractures had a significantly higher risk of delayed wound healing compared with those without previous fragility fractures (OR 2.68; 95% CI 1.11-6.46, p = 0.028). This association still remained after adjusted for all other variables (OR 2.70; 95% CI 1.10-6.60, p = 0.030). Delayed wound healing was not significantly associated with the BMD of the femoral neck.Conclusions: History of fragility fracture may be associated with increased risk of delayed wound healing after tooth extraction in Japanese men and women aged 50-89 years. [ABSTRACT FROM AUTHOR]

SUMMARY: Sargassum ringgoldianm is a canopy‐forming perennial macroalga dominant in a shallow waters along the central Pacific coast of Honshu, Japan, where macroalgal forests have been drastically declining by browsing of herbivorous fish since the 1990s. Accordingly, we tried to reveal seasonal fluctuation of browsing damage on S. ringgoldianum. In the course of the investigation, we found signs of receptacle regeneration in S. rinngoldianum, which has been reported in a few species of the order Fucales. Regenerations occurred most frequently from 3.0 mm to 3.9 mm of the basal part of original receptacles and were also observed at the tips of remaining stalks as well as branchlets that seemed to lose original receptacles. The regenerated receptacles formed antheridia and oogonia, and released eggs from them, suggesting that regenerated receptacles are functional. In addition, no regeneration was observed in only three individuals among 51 plants observed. We show herein a high regenerative ability of wounded receptacles in S. ringgoldianum. This frequent regeneration of functional receptacles is important for the persistence of the population. [ABSTRACT FROM AUTHOR]

Introduction: Keloids are a cutaneous fibroproliferative disorder. Despite the fact that keloids are relatively common lesions, the statistics of patient with keloids especially sex difference remain unknown. To better understand it, we conducted an extensive cross-sectional analysis of a large cohort of patients with keloids (n = 1659). The study showed for the first time that female sex may be an inherent keloid risk factor. Methods: This cross-sectional study of 1659 consecutive patients with keloids who attended a plastic surgery outpatient clinic in Japan in 2014 analyzed age at keloid onset, age at the first medical examination for keloid, and the influence of sex on these variables. Results: In both male and female patients, the keloids were most likely to start in puberty and there was no significant difference in the mode value for age of onset (16 vs. 20 years). Though female patients were twice as prevalent as male patients at nearly all onset ages, female patients predominated over male patients with a gender ratio of 2.7:1 in cases of onset before the age of 15 years. Moreover male and female patients did not differ in terms of the mean ± SD duration between keloid onset and the first medical examination. This finding shows that female patients do not get their keloids examined earlier than male patients. These observations together suggest that female sex may promote early keloid development due to physiological, not social, reasons. Conclusion: This is the first report to suggest that female sex may drive keloidogenesis because of physiological reasons. Individuals were most likely to seek a medical examination almost 10 years after onset, regardless of sex. These findings provide new insight into the importance of sex in the development and progression of keloids. Future studies should address the influence of sex hormones on the keloid. [ABSTRACT FROM AUTHOR]

Hochu‐ekki‐to (HET) is a traditional Japanese herbal (Kampo) medicine for the treatment of severe weakness, loss of appetite, and indigestion in elderly patients and for the prevention of opportunistic infections. The impact of HET on patients with chronic wounds refractory to conventional therapies was investigated in a prospective, randomized trial, including 18 patients divided into medication (7.5 g oral HET per day, n = 9) and control (n = 9) groups. Wound healing during the 12‐week study period was scored based on depth, exudate, size, inflammation/infection, granulation tissue, necrotic tissue, and pocket size. At 12 weeks, wound healing progressed in all nine patients in the medication group, whereas wound healing progressed in only three patients in the control group (significant difference, p < 0.01; relative risk: 3.00). In the medication group, the total score decreased significantly at 8 weeks and later. To the best of our knowledge, this study was the first to show that HET promoted the healing of chronic wounds resistant to conventional treatments. HET may be a choice as an adjunctive therapy for chronic wounds, particularly for patients with malnutrition. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031620). [ABSTRACT FROM AUTHOR]

Summary: In osteoporosis patients receiving antiresorptive medications, stopping the drug and delaying tooth extraction has been suggested to reduce the risk of osteonecrosis of the jaw (ONJ). However, postponing tooth extraction for ≥ 2 months was associated with an increased risk of delayed wound healing beyond 8 weeks after extraction, a risk factor for developing ONJ.Introduction: A long waiting time before tooth extraction could result from concern about a potential increased risk of osteonecrosis of the jaw (ONJ) in osteoporosis patients. We clarified whether a long waiting time before tooth extraction during the past year may be associated with an increased risk of delayed wound healing beyond 8 weeks after tooth extraction, which may be a risk factor of ONJ.Methods: Of 5639 patients aged ≥ 60 years who visited our 20 clinics or hospitals and answered a structured questionnaire, 426 patients (151 men, 275 women) aged 60-96 years comprised the final participants in this study. Self-reported kyphosis was used as a surrogate marker of vertebral fractures. Stepwise logistic regression analysis, adjusted for covariates, was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) for the presence of delayed wound healing longer than 8 weeks after tooth extraction during the past year based on the duration before extraction.Results: Subjects who had waited > 2 months for tooth extraction had a significantly higher risk of delayed wound healing compared with those whose tooth was extracted within 1 month (OR = 7.23; 95% CI = 2.19-23.85, p = 0.001) regardless if antiresorptive medications for osteoporosis were used. The presence of self-reported kyphosis was significantly associated with an increased risk of delayed wound healing (OR = 5.08; 95% CI = 1.11-23.32, p = 0.036).Conclusions: A long waiting time before tooth extraction may be a risk factor for delayed wound healing beyond 8 weeks after extraction in patients aged ≥ 60 years. [ABSTRACT FROM AUTHOR]

Objectives To clarify the surgical methods and the clinical results of subfascial endoscopic perforator surgery in Japan. Methods This study included 1287 limbs of 1091 patients who underwent subfascial endoscopic perforator surgery in 14 hospitals. Simultaneous saphenous vein treatment was performed in 1079 limbs (83.8%), and 118 limbs (9.2%) had deep venous lesions. The venous clinical severity score was calculated before and 6 to 12 months after surgery. The ulcer healing rate and ulcer recurrence rate were calculated cumulatively. Results Preoperative venous clinical severity score was significantly decreased from 10.0 ± 6.6 to 3.1 ± 3.4 (P < .0001) postoperatively. The primary ulcer healing rate was 96.2% (332/345 C6 limbs) at an average follow-up of 47.7 months, and the ulcer recurrence rate was 12.0% (49/393 C5, C6 limbs) at the average follow-up of 46.0 months after the ulcer healed. Conclusion These results indicate that subfascial endoscopic perforator surgery is an alternative to improve the long-lasting disease severity and/or clinical outcome. [ABSTRACT FROM AUTHOR]

Objective: To clarify the surgical indications and the appropriate perioperative management of ischial pressure ulcers (PUs). Method: A two-year prospective, nationwide registry study was carried out across 26 medical institutions in Japan. All participating institutions managed ischial PUs according to the standardisation of total management and surgical application for the refractory decubitus (STANDARDS-I) perioperative protocol. Analysis was conducted on a range of clinically or statistically important variables for the achievement of primary or secondary endpoints: complete wound healing and hospital discharge at three months, and complete wound healing at one month after surgery, respectively. Results: A total of 59 patients took part in the study. All patients underwent surgery for ischial PUs during the study period. Patients who had achieved the primary endpoint had a higer preoperative functional independence measurement (FIM score), a higher 'G' score in the DESIGN-R scale and were more likely to have healed by primary intention. Patients who had achieved the secondary endpoint were more likely to have spastic paralysis, preoperative physiotherapy and localised infection of the wound, among other variables. Conclusion: This survey suggests that preoperative physiotherapy increases the speed of wound healing, and good granulation of the wound bed preoperatively increases the likelihood of woundless discharge from hospital, whereas the existence of comorbidities negatively influences the likelihood of woundless discharge from hospital. The study also suggests that the existence of spastic paralysis, preoperative infection of the wound, or surgical reduction of the ischial tubercle speeds up the healing of the wound. However, the wound failed to heal significantly more often in patients with increasing white blood cell count after surgery. Declaration of interest: The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor β1 (TGF-β1) positively regulates the tenogenic marker genes scleraxis (Scx) and tenomodulin (Tnmd) in mesenchymal progenitors in vitro. However, little is known about the effect of TGF-β1 on the expression of tenogenic markers during rotator cuff (RC) healing in rats. Hypothesis: TGF-β1 improves the biomechanical properties and histological maturity of reparative tissue in a rat RC repair model by stimulating the growth of tenogenic cells. Study Design: Controlled laboratory study. Methods: Adult male Sprague-Dawley rats (N = 180) underwent unilateral supraspinatus tendon-to-bone surgical repair and were randomly treated with a gelatin hydrogel presoaked in TGF-β1 (100 ng) or phosphate-buffered saline. The effects of TGF-β1 on RC healing were investigated at 2, 4, 6, 8, and 12 weeks postoperatively by immunostaining for proliferating cell nuclear antigen, by real-time reverse transcription polymerase chain reaction and in situ hybridization or immunostaining for enthesis-related markers (SRY-box containing gene 9 [Sox9], Scx, and Tnmd), and by real-time reverse transcription polymerase chain reaction and immunostaining for type I and III collagen. At 6 and 12 weeks postoperatively, biomechanical testing, micro–computed tomography, and biochemical analysis were also performed. At 2 and 4 weeks postoperatively, mesenchymal stem cell–related markers, phospho-Smad2, and matrix metalloproteinase 9 (MMP-9) and MMP-13 were assessed by immunostaining. Results: The TGF-β1-treated group had significantly higher ultimate load to failure and tissue volume at 6 and 12 weeks postoperatively and a higher collagen content at 12 weeks compared with the saline group. Tendon-related gene expression, histological maturity, cell proliferation, and mesenchymal stem cell–related marker immunoreactivity were not affected by exogenously administrated TGF-β1 at all time points. In the TGF-β1-treated group, the percentage of phospho-Smad2-positive cells within the healing tissue increased, whereas the expression of MMP-9 and MMP-13 significantly decreased at 2 and 4 weeks postoperatively. Conclusion: TGF-β1 enhances formation of tough fibrous tissues at the healing site by inhibiting MMP-9 and MMP-13 expression to increase collagen accumulation but without the growth of tenogenic lineage cells. Clinical Relevance: These findings suggest that TGF-β1 could be used for enhancing biomechanical strength after RC surgical repair. [ABSTRACT FROM AUTHOR]

We assessed wound healing in patients on hemodialysis (HD) with critical limb ischemia (CLI). This study enrolled 267 patients (including 120 patients on HD and 147 patients not on HD) who underwent endovascular therapy (EVT) for CLI. The primary endpoint was wound-healing rate at two years. Secondary endpoints were time to wound healing, wound recurrence rate, and limb salvage at two years. The percentage of male and young patients was higher in the HD patients ( p < 0.01). A lower patency of the pedal arch after EVT was observed frequently in HD patients ( p < 0.01). The wound-healing rate was significantly lower in HD patients (79.5% vs. 92.4%, p < 0.001). Time to wound healing was significantly longer in HD patients (median 132 days vs. 82 days, p = 0.005). Wound recurrence was observed more frequently in HD patients (25.0% vs. 10.2%, p = 0.007). Limb salvage (72.8% vs. 86.4%, p = 0.002) was significantly lower in HD patients. In a cox proportional hazard model, HD was an independent predictor of wound healing (risk ratio (RR), 0.46; 95% confidence interval (CI), 0.33-0.62; p < 0.001) and wound recurrence (RR, 1.58; 95% CI, 1.11-2.22; p = 0.01). HD was independently associated with lower and delayed wound healing, and wound recurrence. [ABSTRACT FROM AUTHOR]

Objective: The number of patients with foot gangrene caused by critical ischaemia and severe infection is increasing significantly in developed countries. The measurement of perilesional skin blood flow by skin perfusion pressure (SPP) is useful to select the appropriate treatment of gangrenous lesions, in that it is not affected by calcifications of blood vessels. However, the prognosis of a foot ulcer may also be affected by the level of blood sugar and infections. This study aimed to validate the use of SPP in cases of foot gangrene and ulcers in patients with and without diabetes mellitus (DM) and infection. Method: Clinical symptoms, ankle-brachial pressure index (ABPI) and SPP were assessed to evaluate the condition of each foot ulcer. Every foot ulcer was treated as independent, even if a participant had multiple ulcers. All ulcers for which we measured SPP were subject to the analysis. All ulcers were purely ischaemic in nature and were exclusively located on the foot or toes. Results: Data were collected from 117 foot ulcers on 91 toes and feet from 65 patients. Almost all SPP values in healed cases were > 27 mmHg. There were three patients whose ulcers failed to heal by conservative treatments were complicated with severe infection. However, no effect of DM on the relationship between SPP values and prognosis was observed. Logistic regression analysis of all ulcers except for the 5 cases complicated with infection revealed that those with 30 mmHg or lower SPP values are likely to heal by conservative treatment with 23% or lower probability, whereas any ulcer with more than 50 mmHg SPP value and without severe infection may heal without the need for further operations with 80% or higher probability. Conclusion: The combination of SPP and careful evaluation of infection may be a good parameter to decide the appropriate treatment for ischaemic skin ulcers, regardless of the complication of DM. Declaration of interest: Nothing to declare. [ABSTRACT FROM AUTHOR]

Objective: Evaluating bacterial load in pressure ulcers (PUs) is key to combat infection; therefore, using technologies to measure bacterial count can be particularly useful. A rapid bacteria counting system was recently developed and introduced to the wound care field. However, its reliability was not established. This cross-sectional study aimed to evaluate the inter-rater and intra-rater reliability of bacterial count using this rapid counting system. Method: We took bacterial swabs from patients with category I or greater PUs to assess inter- and intra-rater reliability. An assessor swabbed the longest axis of the PU once and bacterial counts were measured using a rapid bacteria counting system. To confirm the inter-rater and intra-rater reliability, intraclass correlation coefficients (ICCs) were calculated. Results: We took 63 and 57 pairs of bacterial counts from 13 patients with 16 category I or greater PUs to assess inter- and intra-rater reliability, respectively. Overall ICCs [95% confidence intervals (CI)] for the bacterial counts were 0.83 [0.73-0.90, p<0.001, inter-rater reliability, n=63], and 0.89 [0.82-0.94, p< 0.001, intra-rater reliability, n=57]. Conclusion: A high level of reliability for counting bacterial numbers in PU sites was confirmed. The results should encourage clinicians and researchers to use this type of device for the real-time assessment of wound bacterial bioburden at the patient's bedside. Declaration of interest: This study was partly supported by a grant-in-aid for Scientific Research A from the Japan Society for the Promotion of Science. The authors have no conflict of interest to declare. [ABSTRACT FROM AUTHOR]

Conclusions:In microsurgical head and neck reconstruction, a higher rate of post-operative wound complication could be predicted by a lower pre-operative neutrophil ratio (< 64.9%), neutrophil-lymphocyte ratio (NLR) (< 3.5), and platelet-lymphocyte ratio (PLR) (< 160). Objectives:To evaluate the predictor of post-operative wound complications in microsurgical head and neck reconstruction. Methods:Patients who were undergoing tumor ablation and microsurgical reconstruction from April 2011 to March 2014 were analyzed retrospectively. The pre-operative hematological data, age, sex, co-morbidities, body mass index (BMI), adjuvant therapies, smoking, operation time, blood loss, total protein, T-stage, and Anesthesiologists Performance Status (ASA-PS) score were collected. Cases of post-operative wound healing failure were reviewed. Results:One hundred and three consecutive patients were enrolled. Among these, the results of 77 patients who were younger than 70 years of age were analyzed. The distributions of the neutrophil ratio (p = .0005), lymphocyte ratio (p = .0166), monocyte ratio (p = .0341), NLR (p = .005), and PLR (p = .008) differed significantly between the patients with and without post-operative wound healing failure. Neutrophil ratio, NLR, and PLR cut-off values of 64.9, 3.5, and 160 were significantly associated with the rate of wound healing failure rate (p = .0002, .00021, .0042, respectively). [ABSTRACT FROM PUBLISHER]

Bacteria have been found to form multicellular aggregates which have collectively been termed 'biofilms.' It is hypothesized that biofilm formation is a means to protect bacterial cells including protection form the immune response of humans. This protective mechanism is believed to explain persistent chronic wound infections. At times, the biofilms are abundant enough to see, and remove by simple wiping. However, recent evidence has shown that the removal of these visible portions are not sufficient, and that biofilms can continue to form even with daily wiping. In this work, we tested an approach to detect the biofilms which are present after clinically wiping or sharp wound debridement. Our method is based on a variation of impression cytology in which a nitrocellulose membrane was used to collect surface biofilm components, which were then differentially stained. In this prospective study, members of an interdisciplinary pressure ulcer team at a university hospital tested our method's ability to predict the generation of wound slough in the week that followed each blotting. A total of 70 blots collected from 23 pressure ulcers produced 27 wounds negative for staining and 43 positive. In the negative blots 55.6% were found to have decreased wound slough, while 81.4% with positive staining had either increase or unchanged wound slough generation. These results lead to an odds ratio of positive blotting cases of 9.37 (95% confidence intervals: 2.47-35.5, p = 0.001) for slough formation; suggesting that the changes in wound slough formation can be predicted clinically using a non-invasive wound blotting method. [ABSTRACT FROM AUTHOR]