Development of a cellular assay as a personalized model for testing chronic wound therapeutics.

Exudates of non-healing wounds contain drivers of pathogenicity. We utilized >800 exudates from non-healing and healing wounds of diverse etiologies, collected by three different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to a) to differentiate between healing and non-healing wounds, b) follow the healing process of individual patients, and c) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically non-healing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo non-healing wound exudates revealed an induction of inflammatory cytokine- and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of non-healing wounds. Testing the wound therapeutics platelet derived growth factor and silver sulfadiazine yielded responses in line with clinical experience and indicate the usefulness of the assay to search for and profile new therapeutics.

Initial antibiotic therapy for postoperative moderate or severe diabetic foot infections: Broad versus narrow spectrum, empirical versus targeted.

AIM: To retrospectively evaluate clinical and microbiological outcomes after combined surgical and medical therapy for diabetic foot infections (DFIs), stratifying between the empirical versus the targeted nature, and between an empirical broad versus a narrow-spectrum, antibiotic therapy. METHODS: We retrospectively assessed the rate of ultimate therapeutic failures for each of three types of initial postoperative antibiotic therapy: adequate empirical therapy; culture-guided therapy; and empirical inadequate therapy with a switch to targeted treatment based on available microbiological results. RESULTS: We included data from 332 patients who underwent 716 DFI episodes of surgical debridement, including partial amputations. Clinical failure occurred in 40 of 194 (20.6%) episodes where adequate empirical therapy was given, in 77 of 291 (26.5%) episodes using culture-guided (and correct) therapy from the start, and in 73 of 231 (31.6%) episodes with switching from empirical inadequate therapy to culture-targeted therapy. Equally, a broad-spectrum antibiotic choice could not alter this failure risk. Group comparisons, Kaplan-Meier curves and Cox regression analyses failed to show either statistical superiority or inferiority of any of the initial antibiotic strategies. CONCLUSIONS: In this study, the microbiological adequacy of the initial antibiotic regimen after (surgical) debridement for DFI did not alter therapeutic outcomes. We recommend that clinicians follow the stewardship approach of avoiding antibiotic de-escalation and start with a narrow-spectrum regimen based on the local epidemiology.

Concurrent Optical- and Magnetic-Stimulation-Induced Changes on Wound Healing Parameters, Analyzed by Hyperspectral Imaging: An Exploratory Case Series.

The effects of concurrent optical and magnetic stimulation (COMS) therapy on wound-healing-related parameters, such as tissue oxygenation and water index, were analyzed by hyperspectral imaging: an exploratory case series. Background: Oedema and inadequate perfusion have been identified as key factors in delayed wound healing and have been linked to reduced mitochondrial respiration. Targeting mitochondrial dysfunction is a promising approach in the treatment of therapy refractory wounds. This sub-study aimed to investigate the effects of concurrent optical and magnetic stimulation (COMS) on oedema and perfusion through measuring tissue oxygenation and water index, using hyperspectral imaging. Patients and methods: In a multi-center, prospective, comparative clinical trial, eleven patients with chronic leg and foot ulcers were treated with COMS additively to Standard of Care (SOC). Hyperspectral images were collected during patient visits before and after treatment to assess short- and long-term hemodynamic and immunomodulatory effects through changes in tissue oxygenation and water index. Results: The average time for wound onset in the eleven patients analyzed was 183 days, with 64% of them being considered unresponsive to SOC. At week 12, the rate of near-complete and complete wound closure was 64% and 45%, respectively. COMS therapy with SOC resulted in an increased short-term tissue oxygenation over the 8-week treatment phase, with oxygen levels decreasing in-between patient visits. The study further found a decrease in tissue water content after the therapy, with a general accumulation of water levels in-between patient visits. This study's long-term analysis was hindered by the lack of absolute values in hyperspectral imaging and the dynamic nature of patient parameters during visits, resulting in high interpatient and intervisit variability. Conclusions: This study showed that COMS therapy as an adjunct to SOC had a positive short-term effect on inflammation and tissue oxygenation in chronic wounds of various etiologies. These results further supported the body of evidence for safety and effectiveness of COMS therapy as a treatment option, especially for stagnant wounds that tended to stay in the inflammatory phase and required efficient phase transition towards healing.

Muscle atrophy in diabetic patients with Charcot foot: a case-control study.

PURPOSE: To evaluate the distribution and severity of muscle atrophy in diabetic patients with active Charcot foot (CF) compared to diabetic patients without CF. Furthermore, to correlate the muscle atrophy with severity of CF disease. MATERIAL/METHODS: In this retrospective study, MR images of 35 diabetic patients (21 male, median:62.1 years ± 9.9SD) with active CF were compared with an age- and gender-matched control group of diabetic patients without CF. Two readers evaluated fatty muscle infiltration (Goutallier-classification) in the mid- and hindfoot. Furthermore, muscle trophic (cross-sectional muscle area (CSA)), intramuscular edema (none/mild versus moderate/severe), and the severity of CF disease (Balgrist Score) were assessed. RESULTS: Interreader correlation for fatty infiltration was substantial to almost perfect (kappa-values:0.73-1.0). Frequency of fatty muscle infiltration was high in both groups (CF:97.1-100%; control:77.1-91.4%), but severe infiltration was significantly more frequent in CF patients (p-values: < 0.001-0.043). Muscle edema was also frequently seen in both groups, but significantly more often in the CF group (p-values: < 0.001-0.003). CSAs of hindfoot muscles were significantly smaller in the CF group. For the flexor digitorum brevis muscle, a cutoff value of 139 mm2 (sensitivity:62.9%; specificity:82.9%) in the hindfoot was found to differentiate between CF disease and the control group. No correlation was seen between fatty muscle infiltration and the Balgrist Score. CONCLUSION: Muscle atrophy and muscle edema are significantly more severe in diabetic patients with CF disease. Muscle atrophy does not correlate with the severity of active CF disease. A CSA < 139 mm2 of the flexor digitorum brevis muscle in the hindfoot may indicate CF disease.

[Think Interdisciplinary to Improve a Complex Multifactorial Gait Disorder of a 28-Year-Old Polio Patient]. / Interdisziplinär denken, um die komplexe multifaktorielle Gangstörung eines 28-jährigen Polio-Patienten zu verbessern.

Think Interdisciplinary to Improve a Complex Multifactorial Gait Disorder of a 28-Year-Old Polio Patient Abstract. Poliomyelitis with the resulting paralytic sequelae is hardly present in Switzerland anymore and if so, only in elderly persons. The last reported case of poliomyelitis in Switzerland was received by the FOPH in 1982. A 28-year-old patient with paralytic poliomyelitis is extremely rare in this country. A combined multifactorial gait disorder with symptomatic hip dysplasia, pronounced leg length shortening and axial malalignment of the leg on the polio-affected side make this case unique and a special interdisciplinary challenge.

Ulcer occurrence on adjacent toes and hallux valgus deformity after amputation of the second toe in diabetic patients.

BACKGROUND: Amputation of the second toe is associated with destabilization of the first toe. Possible consequences are hallux valgus deformity and subsequent pressure ulcers on the lateral side of the first or on the medial side of the third toe. The aim of this study was to investigate the incidence and possible influencing factors of interdigital ulcer development and hallux valgus deformity after second toe amputation. METHODS: Twenty-four cases of amputation of the second toe between 2004 and 2020 (mean age 68 ± 12 years; 79% males) were included with a mean follow-up of 36 ± 15 months. Ulcer development on the first, third, or fourth toe after amputation, the body mass index (BMI) and the amputation level (toe exarticulation versus transmetatarsal amputation) were recorded. Pre- and postoperative foot radiographs were evaluated for the shape of the first metatarsal head (round, flat, chevron-type), the hallux valgus angle, the first-second intermetatarsal angle, the distal metatarsal articular angle and the hallux valgus interphalangeal angle by two orthopedic surgeons for interobserver reliability. RESULTS: After amputation of the second toe, the interdigital ulcer rate on the adjacent toes was 50% and the postoperative hallux valgus rate was 71%. Neither the presence of hallux valgus deformity itself (r = .19, p = .37), nor the BMI (r = .09, p = .68), the shape of the first metatarsal head (r = - .09, p = .67), or the amputation level (r = .09, p = .69) was significantly correlated with ulcer development. The interobserver reliability of radiographic measurements was high, oscillating between 0.978 (p = .01) and 0.999 (p = .01). CONCLUSIONS: The interdigital ulcer rate on the first or third toe after second toe amputation was 50% and hallux valgus development was high. To date, evidence on influencing factors is lacking and this study could not identify parameters such as the BMI, the shape of the first metatarsal head or the amputation level as risk factors for the development of either hallux valgus deformity or ulcer occurrence after second toe amputation. TRIAL REGISTRATION: BASEC-Nr. 2019-01791.

No Difference in Risk of Amputation or Frequency of Surgical Interventions Between Patients With Diabetic and Nondiabetic Charcot Arthropathy.

BACKGROUND: The cause of Charcot neuro-osteoarthropathy (CN) is diabetes in approximately 75% of patients. Most reports on the clinical course and complications of CN focus on diabetic CN, and reports on nondiabetic CN are scarce. No study, to our knowledge, has compared the clinical course of patients initially treated nonoperatively for diabetic and nondiabetic CN. QUESTIONS/PURPOSES: Among patients with CN, are there differences between patients with diabetes and those without in terms of (1) the frequency of major amputation as ascertained by a competing risks survivorship estimator; (2) the frequency of surgery as ascertained by a competing risks survivorship estimator; (3) frequency of reactivation, as above; or (4) other complications (contralateral CN development or ulcers)? METHODS: Between January 1, 2006, and December 31, 2018, we treated 199 patients for diabetic CN. Eleven percent (22 of 199) were lost before the minimum study follow-up of 2 years or had incomplete datasets and could not be analyzed, and another 9% (18 of 199) were excluded for other prespecified reasons, leaving 80% (159 of 199) for analysis in this retrospective study at a mean follow-up duration since diagnosis of 6 ± 4 years. During that period, we also treated 78 patients for nondiabetic Charcot arthropathy. Eighteen percent (14 of 78) were lost before the minimum study follow-up and another 5% (four of 78 patients) were excluded for other prespecified reasons, leaving 77% (60 of 78) of patients for analysis here at a mean of 5 ± 3 years. Patients with diabetic CN were younger (59 ± 11 years versus 68 ± 11 years; p < 0.01), more likely to smoke cigarettes (37% [59 of 159] versus 20% [12 of 60]; p = 0.02), and had longer follow-up (6 ± 4 years versus 5 ± 3 years; p = 0.02) than those with nondiabetic CN. Gender, BMI, overall renal failure, dialysis, and presence of peripheral arterial disease did not differ between the groups. Age difference and length of follow-up were not considered disqualifying problems because of the later onset of idiopathic neuropathy and longer available patient follow-up in patients with diabetes, because our program adheres to the follow-up recommendations suggested by the International Working Group on the Diabetic Foot. Treatment was the same in both groups and included serial total-contact casting and restricted weightbearing until CN had resolved. Then, patients subsequently transitioned to orthopaedic footwear. CN reactivation was defined as clinical signs of the recurrence of CN activity and confirmation on MRI. Group-specific risks of the frequencies of major amputation, surgery, and CN reactivation were calculated, accounting for competing events. Group comparisons and confounder analyses were conducted on these data with a Cox regression analysis. Other complications (contralateral CN development and ulcers) are described descriptively to avoid pooling of complications with varying severity, which could be misleading. RESULTS: The risk of major amputation (defined as an above-ankle amputation), estimated using a competing risks survivorship estimator, was not different between the diabetic CN group and nondiabetic CN group at 10 years (8.8% [95% confidence interval 4.2% to 15%] versus 6.9% [95% CI 0.9% to 22%]; p = 0.4) after controlling for potentially confounding variables such as smoking and peripheral artery disease. The risk of any surgery was no different between the groups as estimated by the survivorship function at 10 years (53% [95% CI 42% to 63%] versus 58% [95% CI 23% to 82%]; p = 0.3), with smoking (hazard ratio 2.4 [95% CI 1.6 to 3.6]) and peripheral artery disease (HR 2.2 [95% CI 1.4 to 3.4]) being associated with diabetic CN. Likewise, there was no between-group difference in CN reactivation at 10 years (16% [95% CI 9% to 23%] versus 11% [95% CI 4.5% to 22%]; p = 0.7) after controlling for potentially confounding variables such as smoking and peripheral artery disease. Contralateral CN occurred in 17% (27 of 159) of patients in the diabetic group and in 10% (six of 60) of those in the nondiabetic group. Ulcers occurred in 74% (117 of 159) of patients in the diabetic group and in 65% (39 of 60) of those in the nondiabetic group. CONCLUSION: Irrespective of whether the etiology of CN is diabetic or nondiabetic, our results suggest that orthopaedic surgeons should use similar nonsurgical treatments, with total-contact casting until CN activity has resolved, and then proceed with orthopaedic footwear. A high frequency of foot ulcers must be anticipated and addressed as part of the treatment approach. LEVEL OF EVIDENCE: Level III, prognostic study.

Salami-Tactics: when is it time for a major cut after multiple minor amputations?

INTRODUCTION: Repetitive minor amputations carry the concomitant risks of multiple surgical procedures, major amputations have physical and economical major drawbacks. The aim of this study was to evaluate whether there is a distinct number of minor amputations predicting a major amputation in the same leg and to determine risk factors for major amputation in multiple minor amputations. MATERIALS AND METHODS: A retrospective chart review including 429 patients with 534 index minor amputations between 07/1984 and 06/2019 was conducted. Patient demographics and clinical data including number and level of re-amputations were extracted from medical records and statistically analyzed. RESULTS: 290 legs (54.3%) had one or multiple re-amputations after index minor amputation. 89 (16.7%) legs needed major amputation during follow up. Major amputation was performed at a mean of 32.5 (range 0 - 275.2) months after index minor amputation. No particular re-amputation demonstrated statistically significant elevated odds ratio (a.) to be a major amputation compared to the preceding amputation and (b.) to lead to a major amputation at any point during follow up. Stepwise multivariate Cox regression analysis revealed minor re-amputation within 90 days (HR 3.8, 95% CI 2.0-7.3, p <0.001) as the only risk factor for major amputation if at least one re-amputation had to be performed. CONCLUSIONS: There is no distinct number of prior minor amputations in one leg that would justify a major amputation on its own. If a re-amputation has to be done, the timepoint needs to be considered as re-amputations within 90 days carry a fourfold risk for major amputation. LEVEL OF EVIDENCE: Retrospective comparative study (Level III).

FeetBack-Redirecting touch sensation from a prosthetic hand to the human foot.

Introduction: Adding sensory feedback to myoelectric prosthetic hands was shown to enhance the user experience in terms of controllability and device embodiment. Often this is realized non-invasively by adding devices, such as actuators or electrodes, within the prosthetic shaft to deliver the desired feedback. However, adding a feedback system in the socket adds more weight, steals valuable space, and may interfere with myoelectric signals. To circumvent said drawbacks we tested for the first time if force feedback from a prosthetic hand could be redirected to another similarly sensitive part of the body: the foot. Methods: We developed a vibrotactile insole that vibrates depending on the sensed force on the prosthetic fingers. This self-controlled clinical pilot trial included four experienced users of myoelectric prostheses. The participants solved two types of tasks with the artificial hands: 1) sorting objects depending on their plasticity with the feedback insole but without audio-visual feedback, and 2) manipulating fragile, heavy, and delicate objects with and without the feedback insole. The sorting task was evaluated with Goodman-Kruskal's gamma for ranked correlation. The manipulation tasks were assessed by the success rate. Results: The results from the sorting task with vibrotactile feedback showed a substantial positive effect. The success rates for manipulation tasks with fragile and heavy objects were high under both conditions (feedback on or off, respectively). The manipulation task with delicate objects revealed inferior success with feedback in three of four participants. Conclusion: We introduced a novel approach to touch sensation in myoelectric prostheses. The results for the sorting task and the manipulation tasks diverged. This is likely linked to the availability of various feedback sources. Our results for redirected feedback to the feet fall in line with previous similar studies that applied feedback to the residual arm. Clinical trial registration: Name: Sensor Glove and Non-Invasive Vibrotactile Feedback Insole to Improve Hand Prostheses Functions and Embodiment (FeetBack). Date of registration: 23 April 2019. Date the first participant was enrolled: 3 September 2021. ClinicalTrials.gov Identifier: NCT03924310.

Mid- and Hindfoot Amputations in Diabetic Patients.

Several surgical options exist to avoid or at least to delay a below-the-knee amputation (BKA). These are the so-called mid- or hindfoot amputations. They are a valuable treatment option in order to maintain the ability to ambulate without major auxiliary means (eg, a prosthesis). Hence, these amputations allow the patients to maintain certain autonomy. The acceptance of these amputations is significantly higher than a BKA, as the body image is less disturbed. The complication rate in hindfoot amputations in diabetic patients is high due to the comorbidities, in particular peripheral arterial disease and polyneuropathy.

Nutritional Interventions May Improve Outcomes of Patients Operated on for Diabetic Foot Infections: A Single-Center Case-Control Study.

Aim: While a patient's nutritional status is known to generally have a role in postoperative wound healing, there is little information on its role as therapy in the multifaceted problem of diabetic foot infections (DFIs). Methods: We assessed this issue by conducting a retrospective case-control cohort study using a multivariate Cox regression model. The nutrition status of the DFI patients was assessed by professional nutritionists, who also orchestrated the nutritional intervention (counselling, composition of the intrahospital food) during hospitalization. Results: Among 1,013 DFI episodes in 586 patients (median age 67 years; 882 with osteomyelitis), 191 (19%) received a professional assessment of their nutrition accompanied by between 1 and 6 nutritional interventions. DFI cases who had professional nutritionists' interventions had a significantly shorter hospital stay, had shorter antibiotic therapies, and tended to fewer surgical debridements. By multivariate analysis, episodes with low Nutritional Risk Status- (NRS-) Scores 1-3 were associated with significantly lower failure rates after therapy for DFI (Cox regression analysis; hazard ratio 0.2, 95% confidence interval 0.1-0.7). Conclusions: In this retrospective cohort study, DFI episodes with low NRS-Score were associated with lower rates of clinical failure after DFI treatment, while nutritional interventions improved the outcome of DFI. We need prospective interventional trials for this treatment, and these are underway.

Correction of hyperglycemia after surgery for diabetic foot infection and its association with clinical outcomes.

OBJECTIVE: Constantly high glycemia levels might influence outcomes in the management of patients undergoing surgery for diabetic foot infections (DFI). In our center for DFI, we performed a case-control study using a multivariate Cox regression model. Patients developing a new DFI could participate in the study several times. RESULTS: Among 1013 different DFI episodes in 586 individual adult patients (type I diabetes 148 episodes [15%], 882 [87%] with osteomyelitis; median antibiotic therapy of 21 days), professional diabetes counselling was provided by a specialized diabetes nurse in 195 episodes (19%). At admission, blood glucose levels were elevated in 110 episodes (11%). Treatments normalized glycemia on postoperative day 3 in 353 episodes (35%) and on day 7 for 321 (32%) episodes. Glycemia levels entirely normalized for 367 episodes (36%) until the end of hospitalization. Overall, treatment of DFI episodes failed in 255 of 1013 cases (25%), requiring surgical revision. By multivariate analysis, neither the provision of diabetes counseling, nor attaining normalizations of daily glycemic levels at day 3, day 7, or overall, influenced the ultimate incidence of clinical failures. Thus, the rapidity or success of achieving normoglycemia do not appear to influence the risk of treatment failure for operated DFI episodes.

Skin biomarkers associated with complex regional pain syndrome (CRPS) Type I: a systematic review.

Despite increasing research, the pathophysiology of Complex Regional Pain Syndrome (CRPS) remains poorly understood. Due to its easy accessibility, the skin represents an ideal approach to gain a better understanding of the underlying processes. We conducted a systematic review of original studies investigating potential biomarkers cutaneous biomarkers in CRPS. Original articles with a minimum level IV of evidence were screened using the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Web of Science Core Collection. Quality assessment was performed using the Methodological Index for Non-Randomized Studies criteria. A total of 11 studies exploring cutaneous biomarkers in 299 CRPS Type I patients were included. The biomarkers identified revealed implications of the following pathophysiological processes: inflammation via interleukins and TNF-a, vascular dysregulation (ET-1/NOx disturbances and hypoxia-high lactate), small fiber neuropathy and hypersensitivity. In terms of skin morphology, evidence suggests: neurite loss, increased expression and disturbed migration of mast cells, as well as an increased expression of α1-adrenoceptors on keratinocytes. The data supporting hypersensitivity had a high risk of bias on quality assessment. The current review has emphasized the current state of knowledge regarding the cutaneous biomarkers in patients suffering from CRPS Type I. Our results serve as a basis for future developments of techniques that would either facilitate diagnosis or may represent therapeutic targets. Trial registration PROSPERO: CRD42020203405. Level of evidence: IV (Systematic Review).

The Role of 99mTc-antigranulocyte SPECT/CT In Community-Acquired Diabetic Foot Osteomyelitis: A Clinical Experience.

BACKGROUND: Magnetic resonance imaging (MRI) is the actual gold standard for the radiological diagnosis of diabetic foot osteomyelitis (DFO). MATERIALS AND METHODS: MRI is not always available and many patients have contraindications. We evaluated the clinical value of 99mTc-antigranulocyte SPECT/CT (AGS) in eight DFO patients who underwent MRI before. RESULTS: The goal was to have a better clinical view on the extent of bone infection and to ameliorate the surgical approach for DFO. However, this additional scintigraphy did not change anything in the clinical approach. CONCLUSION: We shared our experience with AGS for clinical management of complex DFO cases.

Long-term follow-up of conservative treatment of Charcot feet.

BACKGROUND: Charcot arthropathy (CN) can ultimately lead to limb loss despite appropriate treatment. Initial conservative treatment is the accepted treatment in case of a plantigrade foot. The aim of this retrospective study was to investigate the mid- to long-term clinical course of CN initially being treated conservatively, and to identify risk factors for reactivation and contralateral development of CN as well as common complications in CN. METHODS: A total of 184 Charcot feet in 159 patients (median age 60.0 (interquartile range (IQR) 15.5) years, 49 (30.1%) women) were retrospectively analyzed by patient chart review. Rates of limb salvage, reactivation, contralateral development and common complications were recorded. Statistical analysis was performed to identify possible risk factors for limb loss, CN reactivation, contralateral CN development, and ulcer development. RESULTS: Major amputation-free survival could be achieved in 92.9% feet after a median follow-up of 5.2 (IQR 4.25, range 2.2-11.25) years. CN recurrence occurred in 13.6%. 32.1% had bilateral CN involvement. Ulcers were present in 72.3%. 88.1% patients were ambulating in orthopaedic footwear without any further aids. Presence of Diabetes mellitus was associated with reactivation of CN, major amputation and ulcer recurrence. Smoking was associated with ulcer development and necessity of amputations. CONCLUSIONS: With consistent conservative treatment of CN with orthopaedic footwear or orthoses, limb preservation can be achieved in 92.9% after a median follow-up of 5.2 years. Patients with diabetic CN are at an increased risk of developing complications and CN reactivation. To prevent ulcers and amputations, every effort should be made to make patients stop smoking. LEVEL OF EVIDENCE: III, long-term retrospective cohort study.

The association of chronic, enhanced immunosuppression with outcomes of diabetic foot infections.

We investigated if a chronic, enhanced immunosuppressed condition, beyond the immunodeficiency related to diabetes, is associated with clinical failures after combined surgical and medical treatment for diabetic foot infection (DFI). This is a case-control cohort study in a tertiary centre for diabetic foot problems, using case-mix adjustments with multivariate Cox regression models. Among 1013 DFI episodes in 586 patients (median age 67 years; 882 with osteomyelitis), we identified a chronic, enhanced immune-suppression condition in 388 (38%) cases: dialysis (85), solid organ transplantation (25), immune-suppressive medication (70), cirrhosis (9), cancer chemotherapy (15) and alcohol abuse (243). Overall, 255 treatment episodes failed (25%). By multivariate analysis, the presence (as compared with absence) of chronic, enhanced immune-suppression was associated with a higher rate of clinical failures in DFI cases (hazard ratio 1.5, 95% confidence interval 1.1-2.0). We conclude that a chronic, enhanced immune-suppressed state might be an independent risk factor for treatment failure in DFI. Validation of this hypothesis could be useful information for both affected patients and their treating clinicians.

Treatment Failures in Diabetic Foot Osteomyelitis Associated with Concomitant Charcot Arthropathy: The Role of Underlying Arteriopathy.

OBJECTIVE: Therapy for diabetic foot osteomyelitis (DFO) with Charcot neuroosteoarthropathy is challenging. In patients with diabetic Charcot osteomyelitis (DCO), both the anatomic deformity and infection must be addressed. This study assessed the outcomes of DCO therapy and variables associated with treatment failure and compared them with outcomes of DFO cases. METHODS: A single-center, retrospective, case-control study was performed to compare 93 DCO episodes with 530 DFO episodes, using Kaplan-Meier survival curves and multivariate Cox regression analyses. RESULTS: Clinical failure occurred in 21.5% of DCO compared with 22.3% in DFO episodes (p=0.89) and was associated with peripheral arterial disease (PAD) stages 3 or 4 (HR 6.1; CI 2.0-18.1) and chronic treatment with immunosuppressives (HR 7.4; CI 2.0-27.1). Major amputations were significantly more frequent in DCO (28% versus 13.6%; p<0.01) and associated with PAD stages 3 and 4 (HR 8.0; CI 2.2-29.4), smoking (HR 5.4; CI 1.2-24.6), alcohol abuse (HR 3.5; CI 1.1-10.6), and renal dialysis (HR 4.9; CI 1.3-18.9). CONCLUSIONS: Clinical treatment failures did not differ between DCO and DFO. However, patients with DCO underwent major amputation twice as often as those with DFO. Unlike widespread belief, treatment failure in DCO patients may, similar to DFO, be associated with a striking epidemiological link to severe PAD.

Risk factor analysis for above-knee amputation in patients with periprosthetic joint infection of the knee: a case-control study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication following knee arthroplasty. Therapeutic strategies comprise a combination of surgical and antibiotic treatment modalities and aim to eradicate the infection. Sometimes control of the disease can only be attained by above-knee amputation (AKA). While a vast amount of literature exists illuminating predisposing factors for PJI, risk factors favoring the endpoint AKA in this context are sparsely known. METHODS: The purpose of this investigation was to delineate whether patients with PJI of the knee present specific risk factors for AKA. In a retrospective case-control study 11 cases of PJI treated with AKA were compared to 57 cases treated with limb salvage (LS). The minimum follow-up was 2 years. Comorbidities, signs and symptoms of the current infection, factors related to previous surgeries and the implant, microbiology, as well as therapy related factors were recorded. Comparative analysis was performed using student's t-test, chi-square test or Fisher's exact test. Binary differences were calculated using odds ratio (OR). Reoperation frequency was compared using Mann-Whitney U test. In-depth descriptive analysis of 11 amputees was carried out. RESULTS: A total of 68 cases aged 71 ± 11.2 years were examined, 11 of which underwent AKA and 57 had LS. Severe comorbidities (p = 0.009), alcohol abuse (p = 0.015), and preoperative anemia (p = 0.022) were more frequently associated with AKA. Preoperative anemia was found in all 11 amputees (100%) and in 33 of 57 LS patients (58%) with an average preoperative hemoglobin of 99.9 ± 15.1 g/dl compared to 118.2 ± 19.9 g/dl (p = 0.011). No other parameters differed significantly. AKA patients underwent a median of eight (range 2-24) reoperations, LS patients a median of five (range 2-15). CONCLUSION: Factors potentially influencing the outcome of knee PJI are diverse. The indication of AKA in this context remains a rarity and a case-by-case decision. Patient-intrinsic systemic factors such as alcohol abuse, severe comorbidities and preoperative anemia may elevate the individual risk for AKA in the setting of PJI. We recommend that anemia, being a condition well amenable to therapeutic measures, should be given special consideration in management of PJI patients. TRIAL REGISTRATION: This study was registered with Kantonale Ethikkommission Zürich, (BASEC-No. 2016-01048).

How good are clinicians in predicting the presence of Pseudomonas spp. in diabetic foot infections? A prospective clinical evaluation.

Introduction: The most frequently prescribed empirical antibiotic agents for mild and moderate diabetic foot infections (DFIs) are amino-penicillins and second-generation cephalosporins that do not cover Pseudomonas spp. Many clinicians believe they can predict the involvement of Pseudomonas in a DFI by visual and/or olfactory clues, but no data support this assertion. Methods: In this prospective observational study, we separately asked 13 experienced (median 11 years) healthcare workers whether they thought the Pseudomonas spp. would be implicated in the DFI. Their predictions were compared with the results of cultures of deep/intraoperative specimens and/or the clinical remission of DFI achieved with antibiotic agents that did not cover Pseudomonas. Results: Among 221 DFI episodes in 88 individual patients, intraoperative tissue cultures grew Pseudomonas in 22 cases (10%, including six bone samples). The presence of Pseudomonas was correctly predicted with a sensitivity of 0.32, specificity of 0.84, positive predictive value of 0.18 and negative predictive value 0.92. Despite two feedbacks of the interim results and a 2-year period, the clinicians' predictive performance did not improve. Conclusion: The combined visual and olfactory performance of experienced clinicians in predicting the presence of Pseudomonas in a DFI was moderate, with better specificity than sensitivity, and did not improve over time. Further investigations are needed to determine whether clinicians should use a negative prediction of the presence of Pseudomonas in a DFI, especially in settings with a high prevalence of pseudomonal DFIs.