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Acidic pH derived from cancer cells as a double‐edged knife modulates wound healing through DNA repair genes and autophagy


Wound healing is a sequester program that involves diverse cell signalling cascades. Notwithstanding, complete signal transduction pathways underpinning acidic milieu derived from cancer cells is not clear, yet. MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, fluorescein diacetate/propidium iodide staining, and cell cycle flow cytometry revealed that acidic media decreased cell viability and cell number along with enhanced dead cells and S‐phase arrest in normal fibroblasts. Notably, the trends of intracellular reactive oxygen species production and lactate dehydrogenase release significantly increased with time. It seems the downregulation of Klf4 is in part due to acidosis‐induced DNA damage. It promoted cells towards S‐phase arrest and diminished cell proliferation. Klf4 downregulation had a direct correlation with the P53 level while acidic microenvironment promotes cells towards cell death mechanisms including apoptosis and autophagy. Noteworthily, the unchanged levels of Rb and Mlh1 indicated in those genes had no dominant role in the repairing of DNA damage in fibroblasts treated with the acidic microenvironment. Therefore, cells owing to not entering to mitosis and accumulation of DNA damage were undergone cell death to preserve cell homeostasis. Since acidic media decreased the level of tumour suppressor and DNA repair genes and altered the normal survival pathways in fibroblasts, caution should be exercised to not lead to cancer rather than wound healing.

Pressure ulcer Cat. II‐IV incidence on the CuroCell S.A.M. PRO powered reactive air support surface in a high‐risk population: A multicentre cohort study in 12 Belgian nursing homes


The primary objective was to study pressure ulcer (PU) category II‐IV (including suspected deep tissue injury and unstageable PUs) cumulative incidence and PU incidence density, in a 30day observation period, associated with the use of the CuroCell S.A.M. PRO powered reactive air support surface in nursing home residents at risk for PU development. Secondary objectives were to study (a) PU category I cumulative incidence and PU incidence density and (b) user (caregivers and residents) experiences and perceptions of comfort associated with the use of the support surface under study. A multicentre cohort study was set up in 37 care units of 12 Belgian nursing homes. The sample consisted of 191 residents at risk of PU development (Braden score ≤ 17). The cumulative PU incidence was 4.7% (n = 9). The PU incidence density was 1.7/1000 observation days (9 PU/5370 days). The experience and perceptions of comfort analysis revealed that the CuroCell S.A.M. PRO powered reactive air support surface was comfortable for daily use. The mode of action and the quietness of the pump function had a positive impact on sleep quality. Patient comfort and sleep quality are essential criteria in the selection of a support surface.

Translation, cross‐cultural adaptation and validation of the “Cardiff wound impact schedule,” a wound‐specific quality of life instrument, to the native Spanish of Mexican patients

International Wound Journal Translation, cross‐cultural adaptation and validation of the “Cardiff wound impact schedule,” a wound‐specific quality of life instrument, to the native Spanish of Mexican patients


The aim of this study was to translate into Mexican Spanish, cross‐culturally adapt and validate the wound‐specific quality of life (QoL) instrument Cardiff wound impact schedule (CWIS) for Mexican patients. This instrument went through the full linguistic translation process based on the guidelines of Beaton et al (Beaton DE, Bombardier C, Guillemin F, Ferraz MB, Guidelines for the process of cross‐cultural adaptation of self‐report measures, Spine Phila Pa, 1976, 2000, 318‐391). We included a total of 500 patients with chronic leg ulcers. The expert committee evaluated the Face validity and they agreed unanimously that the instrument was adequate to assess the QoL of these patients, covering all relevant areas presented by them. The content validity index obtained was of 0.95. The construct validity demonstrated moderately significant correlations between related sub‐scales of CWIS and SF‐36 (P = .010 to P < .001). The instrument was able to discriminate between healed and unhealed ulcers. The instrument obtained an overall Cronbach's alpha of .952, corresponding to an excellent internal consistency (.903‐.771 alpha range for domains). The CWIS can be appropriately used to assess the health‐related QoL of Mexican patients with chronic leg ulcers.

Innate immune molecule surfactant protein D attenuates sepsis‐induced acute kidney injury through modulating apoptosis and NFκB‐mediated inflammation


The objective of this study is to investigate the mechanism whereby innate immune molecule surfactant protein D (SP‐D) attenuates sepsis‐induced acute kidney injury (AKI) through modulating apoptosis and nuclear factor kappa‐B (NFκB)‐mediated inflammation. In the present study, a mouse sepsis model was established by cecal ligation and puncture in SP‐D knockout (KO) mice and wild‐type (WT) mice. A sham‐operated group was included as the control. The experimental materials were extracted 6 and 24 hours postoperatively. The plasma levels of tumour necrosis factor alpha (TNF‐α) and MCP‐1 were determined by enzyme‐linked immunosorbent assay (ELISA). Apoptosis was measured by double staining with Annexin V/propidium iodide and flow cytometry. The levels of NFκB in renal tissues were measured by ELISA and Western blotting assay. Apoptosis was detected by TUNEL assays. There were no significant differences in plasma TNF‐α levels between the WT sham group and the KO sham group at 6 and 24 hours postoperatively (P < .05), but the levels of TNF‐α in the WT sepsis and KO sepsis groups were significantly higher than those in controls (P < .05). The levels of TNF‐α in the KO sepsis group were significantly higher than those of the WT sepsis group (P < .05). TNF‐α levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The levels of MCP‐1 in the WT sepsis group and the KO sepsis group at 6 and 24 hours postoperatively were significantly higher than those in the control group (P < .05), and MCP‐1 levels in the KO sepsis group were significantly higher than those in the WT sepsis group (P < .05). MCP‐1 levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The expression of SP‐D in WT kidneys was significantly lower at 6 and 24 hours postoperatively (P < .05). The number of TUNEL‐positive cells in the kidneys from septic SP‐D KO mice was significantly higher (P < .05). The levels of NFκB in septic mice were significantly increased at 6 and 24 hours after induction of sepsis compared with the sham‐operated group compared with those of septic SP‐D KO mice and WT mice (P < .05). Innate immune molecule SP‐D significantly decreased plasma levels of inflammatory cytokines in mice and attenuated sepsis‐induced AKI by inhibiting NFκB activity and apoptosis.

The effectiveness of pressure ulcer prevention programme: A comparative study


Hospital‐acquired pressure ulcers (HAPUs) affect patients during hospitalisation, putting patients at risk for further complications. HAPU is one of the hospital quality indicators that require quality initiatives or programmes to minimise its occurrence and consequences. The aim of this study was to assess the effectiveness of a developed quality improvement programme in preventing HAPUs. This is a retrospective comparative study, which tracked the outcomes of pressure ulcer prevention programme (PUPP) for 5 years from 2014 to 2018. Data from 50 441 patients were collected from different units in a tertiary hospital in the eastern region of Saudi Arabia. The programme focused on building a wound care team; providing education to hospital staff, patients, and their families; and continuous data monitoring, in addition to follow‐up visits after discharge. Implementation of the programme was successful showing a statistically significant reduction of HAPUs from 0.20% in 2014 to 0.06% in 2018 (P value <.001). The PUPP was effective in reducing the percentage of pressure ulcer cases. The programme can be extended and implemented in other hospitals.

Systematic review of negative pressure wound therapy for head and neck wounds with fistulas: Outcomes and complications


Fistula formation in head and neck wounds is considered one of the most challenging complications that a head and neck reconstructive surgeon may encounter. The current mainstay of treatment is aggressive surgical debridement followed by vascularised soft tissue coverage. Negative pressure wound therapy (NPWT) has been successfully used for the closure of complicated wounds for decades. This study analysed the outcomes and complications of NPWT in the management of head and neck wounds with fistulas. A systematic search of studies published between January 1966 and September 2019 was conducted using the PubMed, MEDLINE, EMBASE, and SCOPUS databases and using the following key words: “negative pressure wound therapy,” “head and neck,” and “fistula.” We included human studies with abstract and full text available. Analysed endpoints were rate of fistula closure, follow‐up duration, and complications if present. Nine retrospective case series (Level IV evidence) that collectively included 122 head and neck wounds with orocutaneous fistulas, pharyngocutaneous fistulas, and salivary contamination were examined. The number of patients included in each study ranged from 5 to 64. The mode of NPWT varied among the included studies, with most adopting a continuous pressure of −125 mm Hg. Mean durations of NPWT ranged from 3.7 to 23 days, and the reported fistula closure rate ranged from 78% to 100%. To achieve complete wound healing, six studies used additional procedures after stopping NPWT, including conventional wound dressings and vascularised tissue transfer. Information regarding follow up was provided in only three of the nine studies, where patients were followed for 5, 10, and 18 months. No serious adverse events were reported. NPWT for head and neck wounds with fistulas may be considered a safe treatment method that yields beneficial outcomes with a low risk of complications. The current data originated mainly from studies with low levels of evidence characterised by heterogeneity. Therefore, definitive recommendations based on these data cannot be offered. Additional high‐quality trials are warranted to corroborate the findings of this systematic review.

The role of Th1/Th2 cell chemokine expression in hypertrophic scar


The aim of this study was to study the role of Th1/Th2 cell‐associated chemokines in the formation of hypertrophic scars in rabbit ears. Twenty‐six New Zealand white rabbits were used to establish the hypertrophic scar model of rabbit ear and the normal scar model of rabbit's back. Two rabbits were sacrificed on days 0 and 21, 28, 35, 42, 49, 56, and 63 after operation. The specimens were stained with haematoxylin‐eosin (HE). Scar elevation index (SEI) was used to detect the expression of 10 chemokines related to Th1/Th2 cells in both scar formation expressions. Real‐time polymerase chain reaction (PCR) results showed that two chemokines (CXCL10, CXCL12) were highly expressed during the formation of normal scar, and there was almost no expression during the formation of hypertrophic scar (*P < 0.05). The chemokines (CCL2, CCL3, CCL4, CCL5, CCL7, CCL13, CX3CL1) were almost non‐expressed in the formation of normal scars but were expressed for a long time in the formation of hypertrophic scars. The four chemokines, CCL2, CCL4, CCL5, and CX3CL1, maintained a long‐term high expression level during the formation of hypertrophic scars (P < 0.01). There were also three chemokines (CCL14, CCL19, CCL21) that were almost undetectable in normal scarring, but there was transiently low‐level expression (P < 0.05) only during the peak proliferative phase in proliferative scarring. Th1/Th2 cell‐associated chemokines are different in the type, quantity and expression, and maintenance time of rabbit ear hypertrophic scars.

Predictive model to identify the risk of losing protective sensibility of the foot in patients with diabetes mellitus


Diabetic neuropathy is defined as the presence of symptoms and signs of peripheral nerve dysfunction in diabetics. The aim of this study is to develop a predictive logistic model to identify the risk of losing protective sensitivity in the foot. This descriptive cross‐sectional study included 111 patients diagnosed with diabetes mellitus. Participants completed a questionnaire designed to evaluate neuropathic symptoms, and multivariate analysis was subsequently performed to identify an optimal predictive model. The explanatory capacity was evaluated by calculating the R 2 coefficient of Nagelkerke. Predictive capacity was evaluated by calculating sensitivity, specificity, and estimation of the area under the receiver operational curve. Protective sensitivity loss was detected in 19.1% of participants. Variables associated by multivariate analysis were: educational level (OR: 31.4, 95% CI: 2.5‐383.3, P = .007) and two items from the questionnaire: one related to bleeding and wet socks (OR: 28.3, 95% CI: 3.7‐215.9, P = .001) and the other related to electrical sensations (OR: 52.9, 95% CI: 4.3‐643.9, P = .002), which were both statistically significant. The predictive model included the variables of age, sex, duration of diabetes, and educational level, and it had a sensitivity of 81.3% and a specificity of 95.5%. This model has a high predictive capacity to identify patients at risk of developing sensory neuropathy.

Rapid detection of biofilm by wound blotting following sharp debridement of chronic pressure ulcers predicts wound healing: A preliminary study


For optimal wound bed preparation, wound debridement is essential to eliminate bacterial biofilms. However, it is challenging for clinicians to determine whether the biofilm is completely removed. A newly developed biofilm detection method based on wound blotting technology may be useful. Thus, we aimed to investigate the effect of biofilm elimination on wound area decrease in pressure ulcers, as confirmed using the wound blotting method. In this retrospective observational study, we enrolled patients with pressure ulcers who underwent sharp debridement with pre‐ and post‐debridement wound blotting. Biofilm was detected on the nitrocellulose membrane using ruthenium red or alcian blue staining. Patients were included if the test was positive for biofilm before wound debridement. Percent decrease in wound area after 1 week was calculated as an outcome measure. We classified the wounds into a biofilm‐eliminated group and a biofilm‐remaining group based on the post‐debridement wound blotting result. Sixteen wound blotting samples from nine pressure ulcers were collected. The percent decrease in wound area was significantly higher in the biofilm‐eliminated group (median: 14.4%, interquartile range: 4.6%‐20.1%) than in the biofilm‐remaining group (median: −14.5%, interquartile range: −25.3%‐9.6%; P = .040). The presence of remaining biofilms was an independent predictor for reduced percent decrease in wound area (coefficient = −22.84, P = .040). Biofilm‐based wound care guided by wound blotting is a promising measure to help clinicians eliminate bacterial bioburden more effectively for wound area reduction.

Factors influencing the local cure rate of hidradenitis suppurativa following wide local excision


Wide local excision is the gold standard and only potential curative therapy for recalcitrant hidradenitis suppurativa. However, high recurrence rates persist even post‐surgery with little known on the influencing factors for remission. We evaluated the effect of patient, disease, and operative factors on local cure rate of moderate to severe hidradenitis following wide local excision. We performed a retrospective chart review for all patients who had undergone surgical excision of hidradenitis at a university hospital from 2012 to 2018. We identified 79 patients with a total of 220 operative sites. The majority were obese (mean body mass index [BMI] 32.5), female (71%), African‐American (84%), and had a mean age of 31 years. A quarter of operative sites experienced a recurrence (n = 56). Patients who achieved remission had a significantly lower number of affected regions than those who experienced a recurrence (2.3 vs 3.6, P = .0023). Additionally, recurrence rate differed significantly between body locations (P = .0440). Smoking, BMI, Hurley grade, closure method, and excision size did not influence local cure rate. Surgical excision remains a worthy management option for hidradenitis patients with three quarters achieving remission after a single operation. Number of affected regions and location of hidradenitis may play a factor in recurrence.

Use of maggot debridement therapy in hospitalised patients in Germany


Exact data regarding the clinical role of maggot debridement therapy (MDT) for wound care in a specific country are not available. Thus, we analysed the use of MDT in hospitalised patients in Germany. Detailed lists of all hospitalised cases treated with MDT in Germany for the years 2011 to 2016 were provided by the Federal Statistical Office as well as the lists of the 15 most frequent principal and additional diagnoses, respectively, and the 10 most frequent procedures documented with MDT in 2016. Within the 6‐year time period of the study, the number of cases treated with MDT increased by 11% from 4513 in 2011 to 5.017 in 2016. Lower leg and foot were the most frequent anatomic sides of treatment counting up to 83.9% of all cases. In addition, MDT procedures for temporary soft tissue coverage including negative pressure wound therapy were often performed: for treatment of large areas in 36.7% and small areas in 6.2%. 41.3% of all cases treated with MDT had infection with Escherichia coli and 35.9% of all cases with Bacillus fragilis. Our analysis shows a limited use of MDT with a small increase only in the last 6 years in German hospitals. MDT is predominately used to treat foot or leg ulcers.

Cross‐cultural adaptation and psychometric validation of the Patient Scar Assessment Questionnaire to the Spanish language in head and neck surgery


External appearance is the main aesthetic outcome in patients who undergo surgical procedures. Scars located in exposed areas, such as the neck and face, are important for patients. There are at least eight instruments that are used to evaluate postoperative scars, but few fulfil standard methodological conditions. The Patient Scar Assessment Questionnaire (PSAQ) was designed and validated using psychometric methodology. However, this scale has not been translated or validated in the Spanish language. The aim of this study was to undergo a cross‐cultural adaptation and psychometric validation of the PSAQ scale to the Spanish language in patients who underwent head and neck surgery. We followed The Professional Society for Health Economics and Outcomes Research (ISPOR) guidelines for the translation and validation of health‐related scales. Forward and back translations were made by independent translators. We included adult patients who underwent thyroidectomy, parathyroidectomy, parotidectomy, and neck dissection. For the psychometric validation, we used a principal axis exploratory factor analysis with oblimin rotation. A reliability test involving Cronbachs alpha and the item‐total correlation was performed and for the convergent/concurrent validity, we selected the Spanish version of the Vancouver Scar Scale. A total of 180 patients were recruited. Factor analysis showed a five‐factor solution. Cronbachs alpha for the subscales was >0.7. The comparison between the PSAQ appearance subscale and the VSS demonstrated a high correlation (rho = − 0.89). In a sample of 62 patients, the test‐retest evaluation showed high correlation (0.74‐0.99). Our study supports the Spanish version of the PSAQ as a valid, reliable, and reproducible tool to assess the perception and impact of neck scars in Spanish‐speaking patients who undergo head and neck surgery.

Peripheral arterial disease screening and diagnostic practice: A scoping review


Early reliable, valid screening, diagnosis, and treatment improve peripheral arterial disease outcomes, yet screening and diagnostic practices vary across settings and specialties. A scoping literature review described reliability and validity of peripheral ischaemia diagnosis or screening tools. Clinical studies in the PUBMED database January 1, 1970, to August 13, 2018, were reviewed summarising ranges of reliability and validity of peripheral ischaemia diagnostic and screening tools for patients with non‐neuropathic lower leg ischaemia. Peripheral ischaemia screening and diagnostic practices varied in parameters measured such as timing, frequency, setting, ordering clinicians, degree of invasiveness, costs, definitions, and cut‐off points informing clinical and referral decisions. Traditional ankle/brachial systolic blood pressure index <0.9 was a reliable, valid lower leg ischaemia screening test to trigger specialist referral for detailed diagnosis. For patients with advanced peripheral ischaemia or calcified arteries, toe‐brachial index, claudication, or invasive angiographic imaging techniques that can have complications were reliable, valid screening, and diagnostic tools to inform management decisions. Ankle/brachial index testing is sufficiently reliable and valid for use during routine examinations to improve timing and consistency of peripheral ischaemia screening, triggering prompt specialist referral for more reliable, accurate Doppler, or other diagnosis to inform treatment decisions.

Sociodemographic and culture results of paediatric burns


Paediatric burn wounds are challenging conditions to manage for both the doctors and patients and can cause several complications entailing a complicated treatment and recovery process. This study aims to evaluate sociodemographic conditions and antibiogram culture results of paediatric burn wounds. Our study retrospectively evaluated 419 paediatric patients with burns regarding age, gender, burn area and degree, total days spent in hospital, surgical history, final condition, additional disease history, previous attempts, and culture results with their antibiotic resistances, haemogram results, C‐reactive protein results, sociocultural conditions, burned region of the body, and structure of the burn. The prominent observations were an increased rate of incidence in male patients and patients with low socioeconomic conditions, the highest incidence of burns from scalding and domestic accidents, and the highest incidence of third‐degree burns. Furthermore, even though the most encountered burn types were extremity burns, the burn types with the highest culture growth ratio were the perineum burns. The dominant culture growth bacterial group was coagulase‐negative staphylococcus, and the ratio of medication resistance was 67.8%. It is imperative to raise awareness regarding domestic accidents to prevent paediatric burn wounds. The mortality risk can be reduced by carefully monitoring multiple organ involvement and providing timely treatment. Moreover, appropriate wound care is warranted to avoid infection from skin flora.

Retinoic acid-stimulated ERK1/2 pathway regulates meiotic initiation in cultured fetal germ cells

by Sung-Min Kim, Toshifumi Yokoyama, Dylan Ng, Ferhat Ulu, Yukiko Yamazaki

In murine fetal germ cells, retinoic acid (RA) is an extrinsic cue for meiotic initiation that stimulates transcriptional activation of the Stimulated by retinoic acid gene 8 (Stra8), which is required for entry of germ cells into meiotic prophase I. Canonically, the biological activities of RA are mediated by nuclear RA receptors. Recent studies in somatic cells found that RA noncanonically stimulates intracellular signal transduction pathways to regulate multiple cellular processes. In this study, using a germ cell culture system, we investigated (1) whether RA treatment activates any mitogen-activated protein kinase (MAPK) pathways in fetal germ cells at the time of sex differentiation, and (2) if this is the case, whether the corresponding RA-stimulated signaling pathway regulates Stra8 expression in fetal germ cells and their entry into meiosis. When XX germ cells at embryonic day (E) 12.5 were cultured with RA, the extracellular-signal-regulated kinase (ERK) 1/2 pathway was predominantly activated. MEK1/2 inhibitor (U0126) treatment suppressed the mRNA expressions of RA-induced Stra8 and meiotic marker genes (Rec8, Spo11, Dmc1, and Sycp3) in both XX and XY fetal germ cells. Furthermore, U0126 treatment dramatically reduced STRA8 protein levels and numbers of meiotic cells among cultured XX and XY fetal germ cells even in the presence of RA. Taken together, our results suggest the novel concept that the RA functions by stimulating the ERK1/2 pathway and that this activity is critical for Stra8 expression and meiotic progression in fetal germ cells.