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Purpose: The study's objective was to determine the optimal window for anterior cruciate ligament (ACL) reconstruction with respect to quadriceps atrophies and clinical outcome., Methods: For this retrospective, comparative study, 115 patients aged under 35 were included, who received an ACL reconstruction between 2011 and 2016. They were divided into four groups, depending on the time to surgery, to determine the optimal window for reconstruction: (group 1: ≤21 d, group 2: <21d-56d≥, group 3: >56d-100d≥, group 4: >100d). Follow-up was performed one month postoperatively, after a mean of 4.9 (±5.3) months, and after a mean of 3.5 (±1.4) years. Primary endpoints included quadriceps muscle status, range of motion (ROM), pain, swelling, the International Knee Documentation Committee Subjective Knee Form (IKDC), the Lysholm-Score, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Tegner-Activity-Scale (TAS)., Results: Significantly more quadriceps atrophies were observed in group 1 and group 4, representing reconstructions earlier than 21 and later than 100 days (29% and 41% vs. 9%; p = 0.032). The measurements of knee extension (p = 0.082) and ROM (p = 0.123) were comparable in all groups. Group 1 showed the least pain (0% vs. 15%; p = 0.285) and swelling (0% vs. 23%; p = 0.077) compared to all other groups one month postoperatively. A comparison of postoperative clinical scores revealed no significant differences, with group 1 exhibiting the lowest TAS levels., Conclusion: In patients who underwent ACL reconstruction within three weeks or after more than 100 days, a significantly higher incidence of quadriceps atrophy was observed, possibly attributable to the initial inflammatory phase or the delayed reconstruction affecting quadriceps function. However, this impairment may not be observable in elite athletes who undergo reconstruction within hours of the injury., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Patrick Sadoghi receives industry grants from Depuy Synthes, Alphamed Medizintechnik Fischer GmbH, and Medacta International SA not related to the submitted work. All other authors declare that there are no potential conflicts of interest related to the study authors and corresponding organizations, and publication of the paper. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Widhalm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Anterior Cruciate Ligament (ACL) rupture is a very common knee injury during sport activities. Landing after jump is one of the most prominent human body movements that can lead to such an injury. The landing-related ACL injury risk factors have been in the spotlight of research interest. Over the years, researchers and clinicians acquire knowledge about human movement during daily-life activities by organizing complex in vivo studies that feature high complexity, costs and technical and most importantly physical challenges. In an attempt to overcome these limitations, this paper introduces a computational modeling and simulation pipeline that aims to predict and identify key parameters of interest that are related to ACL injury during single-leg landings. We examined the following conditions: a) landing height, b) hip internal and external rotation, c) lumbar forward and backward leaning, d) lumbar medial and lateral bending, e) muscle forces permutations and f) effort goal weight. Identified on related research studies, we evaluated the following risk factors: vertical Ground Reaction Force (vGRF), knee joint Anterior force (AF), Medial force (MF), Compressive force (CF), Abduction moment (AbdM), Internal rotation moment (IRM), quadricep and hamstring muscle forces and Quadriceps/Hamstrings force ratio (Q/H force ratio). Our study clearly demonstrated that ACL injury is a rather complicated mechanism with many associated risk factors which are evidently correlated. Nevertheless, the results were mostly in agreement with other research studies regarding the ACL risk factors. The presented pipeline showcased promising potential of predictive simulations to evaluate different aspects of complicated phenomena, such as the ACL injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Moustridi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anterior cruciate ligament (ACL) rupture represents one of the most recurrent knee injuries in soccer players. To allow a safe return to sport after ACL reconstruction, standardised and reliable procedures/criteria are needed. In this context, wearable sensors are gaining momentum as they allow obtaining objective information during sport-specific and in-the-field tasks. This paper aims at proposing a sensor-based protocol for the assessment of knee stability and at quantifying its reliability. Seventeen soccer players performed a single leg squat and a cross over hop test. Each participant was equipped with two magnetic-inertial measurement units located on the tibia and foot. Parameters related to the knee stability were obtained from linear acceleration and angular velocity signals. The intraclass correlation coefficient (ICC) and minimum detectable change (MDC) were calculated to evaluate each parameter reliability. The ICC ranged from 0.29 to 0.84 according to the considered parameter. Specifically, angular velocity-based parameters proved to be more reliable than acceleration-based counterparts, particularly in the cross over hop test (average ICC values of 0.46 and 0.63 for acceleration- and angular velocity-based parameters, respectively). An exception was represented, in the single leg squat, by parameters extracted from the acceleration trajectory on the tibial transverse plane (0.60≤ICC≤0.76), which can be considered as promising candidates for ACL injury risk assessment. Overall, greater ICC values were found for the dominant limb, with respect to the non-dominant one (average ICC: 0.64 and 0.53, respectively). Interestingly, this between-limb difference in variability was not always mirrored by LSI results. MDC values provide useful information in the perspective of applying the proposed protocol on athletes with ACL reconstruction. Thus, The outcome of this study sets the basis for the definition of reliable and objective criteria for return to sport clearance after ACL injury., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Accurate assessment of anterior cruciate ligament (ACL) function is vital for guiding treatment. Nevertheless, the presence of tibial subluxation in the neutral position of a patient with an ACL injury may potentially introduce a confounding factor. This study aims to investigate whether tibial subluxation in the neutral position affects the diagnosis of anterior instability in patients with ACL injuries, potentially impacting the reliability and diagnostic accuracy of stress radiography. Methods: This study included 88 patients: 30 with acute complete ACL tears (acute group), 28 with chronic complete ACL tears (chronic group), and 30 patients who underwent knee arthroscopic surgery other than ACL reconstruction (control group). Side-to-side differences (SSD) in stress radiography were measured using the Telos load status and the SSD of the gap between the Telos load and unload statuses. Diagnostic accuracy of the two methods was assessed using areas under the receiver operating characteristic curves (AUCs). Results: The load SSD (5.92 ± 5.28 mm) was higher than the load-unload SSD (4.27 ± 5.99 mm) in the chronic group (P = 0.017). The load SSD demonstrated a significantly higher diagnostic value than that of the load-unload SSD in the combined group (AUC = 0.920 vs. 0.830; P = 0.012) and chronic group (AUC = 0.913 vs. 0.754; P = 0.002). After adjusting the symptoms for radiographic duration from 6 to 3 months in the chronic group, the load SSD exhibited a significantly higher diagnostic value (AUC = 0.902) than that of the load-unload SSD (AUC = 0.740; P < 0.001). Conclusion: The load SSD provides superior diagnostic accuracy compared to the load-unload SSD in ACL tear cases, where static anterior tibial subluxation may result in false negatives. Although load-unload SSD may have diagnostic value within the first 3 months post-injury, the load SSD method provides a reliable assessment of ACL function for patients beyond this timeframe. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) tear is common in military setting; such an injury increase institutional costs and workforce strain, however, few studies have investigated the mechanism and associated factors of ACL tear specifically in a military setting. The aim of this study was to investigate the prevalence and mechanisms of ACL tears in military personnel at a military referral hospital in Iran. Material and methods: This cross-sectional study examined 402 military personnel who presented with knee complaints at a single referral Iranian military hospital. The ACL injury prevalence and mechanisms were assessed by physical examination, medical records, and magnetic resonance imaging (MRI) of the knee. Data were collected by an orthopedic resident. Results: Of the total 402 patients, 285 were diagnosed with ACL tears; the prevalence was 70.9%. The most common mechanism leading to ACL tear was noncontact events. The knee changing direction-knee pivoting (54%) was the most frequent lower limb status, followed by a fall with the knee in valgus position (20.7%). The most commonly associated activity was military training (63.9%) and sports activities (32.6%). The incidence of ACL injuries was higher in soldiers compared with officers during military training, but higher in officers during sports exercises (P = 0.002). Common associated injuries involved the knee meniscus and cartilage. Conclusion: The findings support those of previous studies, that in military personnel, the most common knee injury is damage to the ACL, most frequently through noncontact events, specifically knee pivoting, during military activities rather than sports and among soldiers. These findings help develop ACL injury prevention programs. [ABSTRACT FROM AUTHOR]

Background/objective: The menisci of the mammalian knee joint balance the incongruence between femoral condyle and tibial plateau and thus menisci absorb and distribute high loads. Degeneration processes of the menisci lead to pain syndromes in the knee joint. The origin of such degenerative processes on meniscal tissue is rarely understood and may be described best as an imbalance of anabolic and catabolic metabolism. A standardized animal model of meniscal degeneration is needed for further studies. The aim of the current study was to develop a porcine animal model with early meniscal degeneration., Material and Methods: Resection of the anterior cruciate ligament (ACLR) was performed on the left knee joints of eight Göttingen minipigs. A sham operation was carried out on the right knee joint. The grade of degeneration was determined 26 weeks after the operation using histology and magnetic resonance imaging (MRI). Furthermore, the expression of 14 genes which code for extracellular matrix proteins, catabolic matrix metalloproteinases and inflammation mediators were analyzed., Results: Degenerative changes were detected by a histological analysis of the medial meniscus after ACLR. These changes were not detected by MRI. In terms of their gene expression profile, these degenerated medial menisci showed a significantly increased expression of COL1A1., Conclusion: This paper describes a new animal model for early secondary meniscal degeneration in the Göttingen minipig. Histopathological evidence of the degenerative changes could be described. This early degenerative changes could not be seen by NMR imaging.

One of the most common knee injuries is the Anterior Cruciate Ligament (ACL) rupture with severe implications on knee stability. The usual treatment is the ACL Reconstruction (ACLR) surgery where the surgeon replaces the torn ligament with a graft in an effort to restore knee kinematics. In case of excessive rotatory instability, Lateral Extra—Articular Tenodesis (LET) can be performed in combination with ACLR. Additionally, LET appears to reduce ACLR graft forces minimizing graft failure chances. However, there are concerns about overconstraining physiological rotation. To gain insight in this controversial topic, we developed an automatic, open-source tool to create a series of Finite Element (FE) models attempting to investigate the interactions of ACLR and LET through simulation. We started by creating a validated model of the healthy knee joint that served as reference for subsequent FE simulations. Then, we created FE models of standalone ACLR and combined ACLR—LET. Each model was assessed by applying a loading profile that resembles the reduction phase of the Pivot—Shift clinical exam. We measured the External Tibia Rotation (ETR), the Posterior Tibia Translation (PTT) of the lateral tibial compartment, and the ACLR graft stress developed around the femoral tunnel insertion site. We observed the following: a) LET reduces ETR and PTT compared to isolated ACLR, b) combined ACLR—LET is more sensitive to LET graft pretension with lower values showcasing performance closer to the healthy joint, c) LET reduces ACLR graft forces for the same pretension values, d) LET exhibits significant overconstraint for higher pretension values. In general, these findings are in agreement with relevant clinical studies and accentuate the potential of the developed framework as a tool that can assist orthopaedists during surgery planning. We provide open access for the FE models of this study to enhance research transparency, reproducibility and extensibility. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) rupture is an important condition of the human knee. Second ruptures are common and societal costs are substantial. Canine cranial cruciate ligament (CCL) rupture closely models the human disease. CCL rupture is common in the Labrador Retriever (5.79% prevalence), ~100-fold more prevalent than in humans. Labrador Retriever CCL rupture is a polygenic complex disease, based on genome-wide association study (GWAS) of single nucleotide polymorphism (SNP) markers. Dissection of genetic variation in complex traits can be enhanced by studying structural variation, including copy number variants (CNVs). Dogs are an ideal model for CNV research because of reduced genetic variability within breeds and extensive phenotypic diversity across breeds. We studied the genetic etiology of CCL rupture by association analysis of CNV regions (CNVRs) using 110 case and 164 control Labrador Retrievers. CNVs were called from SNPs using three different programs (PennCNV, CNVPartition, and QuantiSNP). After quality control, CNV calls were combined to create CNVRs using ParseCNV and an association analysis was performed. We found no strong effect CNVRs but found 46 small effect (max(T) permutation P<0.05) CCL rupture associated CNVRs in 22 autosomes; 25 were deletions and 21 were duplications. Of the 46 CCL rupture associated CNVRs, we identified 39 unique regions. Thirty four were identified by a single calling algorithm, 3 were identified by two calling algorithms, and 2 were identified by all three algorithms. For 42 of the associated CNVRs, frequency in the population was <10% while 4 occurred at a frequency in the population ranging from 10–25%. Average CNVR length was 198,872bp and CNVRs covered 0.11 to 0.15% of the genome. All CNVRs were associated with case status. CNVRs did not overlap previous canine CCL rupture risk loci identified by GWAS. Associated CNVRs contained 152 annotated genes; 12 CNVRs did not have genes mapped to CanFam3.1. Using pathway analysis, a cluster of 19 homeobox domain transcript regulator genes was associated with CCL rupture (P = 6.6E-13). This gene cluster influences cranial-caudal body pattern formation during embryonic limb development. Clustered genes were found in 3 CNVRs on chromosome 14 (HoxA), 28 (NKX6-2), and 36 (HoxD). When analysis was limited to deletion CNVRs, the association was strengthened (P = 8.7E-16). This study suggests a component of the polygenic risk of CCL rupture in Labrador Retrievers is associated with small effect CNVs and may include aspects of stifle morphology regulated by homeobox domain transcript regulator genes. [ABSTRACT FROM AUTHOR]

The purpose was to evaluate the dynamic knee control during a drop jump test following injury of the anterior cruciate ligament injury (ACL) using finite helical axes. Persons injured 17–28 years ago, treated with either physiotherapy (ACLPT, n = 23) or reconstruction and physiotherapy (ACLR, n = 28) and asymptomatic controls (CTRL, n = 22) performed a drop jump test, while kinematics were registered by motion capture. We analysed the Preparation phase (from maximal knee extension during flight until 50 ms post-touchdown) followed by an Action phase (until maximal knee flexion post-touchdown). Range of knee motion (RoM), and the length of each phase (Duration) were computed. The finite knee helical axis was analysed for momentary intervals of ~15° of knee motion by its intersection (ΔAP position) and inclination (ΔAP Inclination) with the knee's Anterior-Posterior (AP) axis. Static knee laxity (KT100) and self-reported knee function (Lysholm score) were also assessed. The results showed that both phases were shorter for the ACL groups compared to controls (CTRL-ACLR: Duration 35±8 ms, p = 0.000, CTRL-ACLPT: 33±9 ms, p = 0.000) and involved less knee flexion (CTRL-ACLR: RoM 6.6±1.9°, p = 0.002, CTRL-ACLR: 7.5 ±2.0°, p = 0.001). Low RoM and Duration correlated significantly with worse knee function according to Lysholm and higher knee laxity according to KT-1000. Three finite helical axes were analysed. The ΔAP position for the first axis was most anterior in ACLPT compared to ACLR (ΔAP position -1, ACLPT-ACLR: 13±3 mm, p = 0.004), with correlations to KT-1000 (rho 0.316, p = 0.008), while the ΔAP inclination for the third axis was smaller in the ACLPT group compared to controls (ΔAP inclination -3 ACLPT-CTRL: -13±5°, p = 0.004) and showed a significant side difference in ACL injured groups during Action (Injured-Non-injured: 8±2.7°, p = 0.006). Small ΔAP inclination -3 correlated with low Lysholm (rho 0.391, p = 0.002) and high KT-1000 (rho -0.450, p = 0.001). Conclusions Compensatory movement strategies seem to be used to protect the injured knee during landing. A decreased ΔAP inclination in injured knees during Action suggests that the dynamic knee control may remain compromised even long after injury. [ABSTRACT FROM AUTHOR]

Introduction: Knee pain is common in adolescents and adults and is associated with an increased risk of developing knee osteoarthritis. The aim of this systematic review was to gather and appraise the cost-effectiveness of treatment approaches for non-osteoarthritic knee pain conditions. Method: A systematic review was conducted according to the PRISMA guidelines and registered on PROSPERO (CRD42016050683). The literature search was done in MEDLINE via PubMed, EMBASE, The Cochrane Library, and the National Health Service Economic Evaluation Database. Study selection was carried out by two independent reviewers and data were extracted using a customized extraction form. Study quality was assessed using the Consensus on Health Economic Criteria list. Results: Fifteen studies were included. The majority regarded the treatment of anterior cruciate ligament (ACL) injuries, but we also identified studies evaluating other knee pain conditions such as meniscus injuries, cartilage defects, and patellofemoral pain syndrome. Study interventions were categorized as surgical or non-surgical interventions. The surgical interventions included ACL reconstruction, chondrocyte implantation, meniscus scaffold procedure, meniscal allograft transplantation, partial meniscectomy, microfracture, and different types of autografts and allografts. The non-surgical management consisted of physical therapy, rehabilitation, exercise, counselling, bracing, and advice. In general, for ACL injuries surgical management alone or in combination with rehabilitation appeared to be cost-effective. The quality of the economic evaluations was of moderate to high quality. Conclusion: There was insufficient evidence to give a firm overview of cost-effective interventions for non-osteoarthritic knee pain, but surgical treatment of acute ACL injury appeared cost-effective. There is very little data regarding the cost-effectiveness of non-surgical interventions for non-traumatic knee conditions. [ABSTRACT FROM AUTHOR]

Aims: To translate the English version of Tegner Activity Score into a Simplified-Chinese version (Tegner-C) and evaluate its psychometric properties. Methods: Tegner-C was cross-culturally adapted according to established guidelines. The validity and reliability of Tegner-C were assessed in 78 participants, with 19–20 participants in each of the four groups: before anterior cruciate ligament reconstruction (pre-ACLR) group, 2–3 months after ACLR group, 3–12 months after ACLR group, and healthy control group. Each participant was asked to complete the Tegner-C and Chinese version of International Knee Documentation Committee Subjective Knee Form (IKDC-SKF-C) twice, with an interval of 5±2 days. Intra-class correlation coefficient (ICC2, 1) was used to assess the reliability and Spearman’s rank correlation was used for construct validity. Results: The ICC2,1 was higher than 0.90 for all groups except in the pre-ACLR group, for which the ICC2,1 was 0.71 (0.41, 0.87) (All with p<0.001). The absolute reliability as evaluated by the smallest detectable change was 0.43, 2.12, 0.89, and 0.44 for the healthy control group, pre-ACLR group, 2–3 months after ACLR group, and 3–12 months after ACLR group, respectively. Neither a ceiling effect nor a floor effect was observed for any group. Significant difference was observed for both Tegner-C and IKDC-SKF-C scores between the control and the other three groups (all with p<0.001), and between pre-ACLR and the 2–3 months after ACLR group (p<0.001). Conclusions: Tegner-C demonstrated comparable psychometric properties to the original English version and thus is reliable and valid for Chinese-speaking patients with ACL injury. [ABSTRACT FROM AUTHOR]

Background: Hamstring strain and anterior cruciate ligament injuries are, respectively, the most prevalent and serious non-contact occurring injuries in team sports. Specific biomechanical and neuromuscular variables have been used to estimate the risk of incurring a non-contact injury in athletes. Objective: The aim of this study was to systematically review the evidences for the effectiveness of injury prevention protocols to modify biomechanical and neuromuscular anterior cruciate and/or hamstring injuries associated risk factors in uninjured team sport athletes. Data Sources: PubMed, Science Direct, Web of Science, Cochrane Libraries, U.S. National Institutes of Health clinicaltrials.gov, Sport Discuss and Google Scholar databases were searched for relevant journal articles published until March 2015. A manual review of relevant articles, authors, and journals, including bibliographies was performed from identified articles. Main Results: Nineteen studies were included in this review. Four assessment categories: i) landing, ii) side cutting, iii) stop-jump, and iv) muscle strength outcomes, were used to analyze the effectiveness of the preventive protocols. Eight studies using multifaceted interventions supported by video and/or technical feedback showed improvement in landing and/or stop-jump biomechanics, while no effects were observed on side-cutting maneuver. Additionally, multifaceted programs including hamstring eccentric exercises increased hamstring strength, hamstring to quadriceps functional ratio and/or promoted a shift of optimal knee flexion peak torque toward a more open angle position. Conclusions: Multifaceted programs, supported by proper video and/or technical feedback, including eccentric hamstring exercises would positively modify the biomechanical and or neuromuscular anterior cruciate and/or hamstring injury risk factors. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament injury is a debilitating pathology which may alter lower limb coordination pattern in both intact and affected lower extremities during activities of daily living. Emerging evidence supports the notion that kinematic variables may not be a good indicator to differentiate patients with anterior cruciate ligament deficiency during step descent task. The aim of the present study was to examine alterations in kinematics as well as coordination patterns and coordination variability of both limbs of these patients during a single step descent task. Continuous relative phase technique was used to measure coordination pattern and coordination variability between a group of anterior cruciate ligament deficient (n = 23) and a healthy control group (n = 23). A third order polynomial Curve fitting was utilized to provide a curve that best fitted to the data points of coordination pattern and coordination variability of the healthy control group. This was considered as a reference to compare to that of patient group using nonlinear regression analysis. The results of the present study demonstrated an altered coordination pattern of the supporting shank-thigh and the stepping foot-shank couplings in anterior cruciate ligament deficient subjects. It was further noticed that there was an increased coordination variability in foot-shank and shank-thigh couplings of both supporting and stepping legs. There was no significant difference in the hip, knee and ankle joints kinematics in either side of these patients. Anterior cruciate ligament deficient individuals showed altered strategies in both intact and affected legs, with increased coordination variability. Kinematic data did not indicate any significant difference between the two groups. It could be concluded that more sophisticated dynamic approach such as continuous relative phase would uncover discrepancies between the healthy and anterior cruciate ligament deficient individuals. [ABSTRACT FROM AUTHOR]

The risk of anterior cruciate ligament (ACL) injury and re-injury is greater for women than men. Among other factors, compositional differences may play a role in this differential risk. Patellar tendon (PT) autografts are commonly used during reconstruction. The aim of the study was to compare protein expression in male and female ACL and PT. We hypothesized that there would be differences in key structural components between PT and ACL, and that components of the proteome critical for response to mechanical loading and response to injury would demonstrate significant differences between male and female. Two-dimensional liquid chromatography-tandem mass spectrometry and a label-free quantitative approach was used to identify proteomic differences between male and female PT and ACL. ACL contained less type I and more type III collagen than PT. There were tissue-specific differences in expression of proteoglycans, and ACL was enriched in elastin, tenascin C and X, cartilage oligomeric matrix protein, thrombospondin 4 and periostin. Between male and female donors, alcohol dehydrogenase 1B and complement component 9 were enriched in female compared to male. Myocilin was the major protein enriched in males compared to females. Important compositional differences between PT and ACL were identified, and we identified differences in pathways related to extracellular matrix regulation, complement, apoptosis, metabolism of advanced glycation end-products and response to mechanical loading between males and females. Identification of proteomic differences between male and female PT and ACL has identified novel pathways which may lead to improved understanding of differential ACL injury and re-injury risk between males and females. [ABSTRACT FROM AUTHOR]

Background: Anthroponotic cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL. Methodology/Principal Findings: From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC) followed by daily moist-wound-treatment (MWT) with polyacrylate hydrogel with (group I) or without (group II) pharmaceutical sodium chlorite (DAC N-055). Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immuno)histopathological analyses were taken prior to EC (1st), after wound closure (2nd) and after 6 months (3rd). The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d) and II (54 patients, 42 d; p = 0.83). In patients with Leishmania-positive 2nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08). Superinfections occurred in both groups at the same rate (8.8%). Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158) were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes. Conclusions/Significance: Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of wound closure in a subgroup of patients with parasite persistence warrant future studies on the activity of DAC N-055. Trial Registration: ClinicalTrails.gov NCT00947362 Author Summary: In many countries of the Middle East such as Afghanistan, cutaneous leishmaniasis is a highly prevalent, chronic and stigmatizing skin disease. Poor hygiene conditions frequently aggravate the lesions due to bacterial and fungal superinfections. Classical treatments with injections of pentavalent antimony are hampered by costs, side effects, resistance development, supply and manufactural quality problems. In the present study on Afghan patients with Leishmania tropica-induced skin lesions we evaluated the clinical effect of an initial removal of lesion tissue by electrocoagulation using a bipolar high-frequency electrosurgery instrument, followed by daily moist wound treatment with or without a preparation of pharmaceutical sodium chlorite (DAC N-055). DAC N-055 is a compound with anti-infective, immunomodulatory and tissue repair-promoting effects. Our analysis revealed that the carefully performed moist wound treatment led to a rapid healing of the wounds within an average period of 6 weeks, even in the absence of the sodium chlorite preparation. This is considerably faster than the time spans previously reported for local or systemic antimony treatment. We believe that the current standard for local care of chronic wounds should also be applied to Leishmania skin lesions. If combined with an initial single high-frequency electrocoagulation, it is a highly effective, inexpensive and well-tolerated treatment option for cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: Kabul, Afghanistan, is the largest focus of anthroponotic cutaneous leishmaniasis (ACL) in the world. ACL is a protozoan disease transmitted to humans by the bite of phlebotomine sand flies. Although not fatal, ACL can lead to considerable stigmatization of affected populations. Methods: Using data from a standardized survey of 872 households in 4 wards of Kabul, Afghanistan, univariate and multivariate logistic regression analyses tested associations between presence of active ACL and ACL scars with 15 household-level variables. Findings: Univariate analyses showed that active ACL was positively associated with household member's age, ACL prevalence, and brick wall type, but negatively associated with household number of rooms, bednet use, and proportion of windows with screens. Multivariate analysis showed a positive association between active ACL and household member's age, ACL prevalence, and brick wall type, and a negative association with household proportion of windows with screens. Conclusion: Household-level charateristics were shown to be risk factors for ACL. Monitoring a selected number of household characteristics could assist in rapid assessments of household-level variation in risk of ACL. ACL prevention and control programs should consider improving house construction, including smoothing of walls and screening of windows. Author Summary: Cutaneous leishmaniasis is a vector-borne protozoan disease that is characterized by cutaneous lesions which develop at the site of the insect bite. Lesions can vary in severity, clinical appearance, and time to cure; in a proportion of patients lesions can become chronic, leading to disfiguring mucosal leishmaniasis or leishmaniasis recidvans. Albeit not fatal, cutaneous leishmaniasis can have a significant social impact as it may lead to severe stigmatisation of affected individuals when lesions or scars occur on the face and exposed extremeties. Over the last 10–20 years there has been an increase in the number of leishmaniasis cases reported in South Asia, particularly in Afghanistan. Little is known about the household-level risk factors for infection and disease. Here we confirm previous reports that had shown the association of cutaneous leishmaniasis with age and clustering of cases at the household-level. Additionally, we show that risk of cutaneous leishmaniasis is associated with household construction (i.e. brick walls) and design (i.e. proportion of windows with screens). [ABSTRACT FROM AUTHOR]