Diagnostic Performance of Atherogenic Index of Plasma for Predicting Diabetic Foot Osteomyelitis with Peripheral Artery Disease.

Background: This study aims to assess the atherogenic index of plasma (AIP) diagnostic value in detecting diabetic foot osteomyelitis (DFO) among patients with diabetic foot ulcers (DFUs). Methods: A prospective cohort study was conducted on 80 patients with DFUs and suspected DFO between January 2022 and December 2023. The primary outcome measures included the diagnosis of DFO, determined by positive microbiological analysis results from bone samples and its correlation with the AIP. Receiver operating characteristic (ROC) curves were utilized to select the optimal diagnostic cut-off points for AIP and post hoc analysis was performed to evaluate the difference in the AIP for diagnosing DFO in patients with and without peripheral arterial disease (PAD). Results: The diagnostic potential for DFO in PAD patients of AIP-1 (Log TC/HDL) showed an AUC of 0.914 (p < 0.001 [0.832-0.996]), leading to a sensitivity of 83% and a specificity of 85%. By contrast, AIP-2 (Log TG/HDL) demonstrated a slightly lower AUC of 0.841 (p < 0.001 [0.716-0.967]), leading to a sensitivity of 76% and a specificity of 74%. Conclusions: The AIP tool, with its ideal blend of sensitivity and specificity, aids in predicting DFO effectively. Therefore, clinicians should consider using AIP for patients suffering from PAD and associated DFO.

Diagnostic Performance of Ultrasonography for Diabetic Foot Osteomyelitis.

Objective: This study aims to analyze the potential diagnostic capability of ultrasonography (US) in detecting diabetic foot osteomyelitis (DFO) in patients with diabetic foot ulcers (DFUs). Approach: A 1-year prospective study was conducted on 47 consecutive patients with active DFUs and suspicion of DFO at a specialized diabetic foot unit. The following ultrasonographic features were evaluated at baseline: (1) periosteal reaction; (2) periosteal elevation; (3) cortical disruption; (4) sequestrum; and (5) positive power Doppler. The primary outcome measure aimed to establish the effectiveness of ultrasonographic features compared with aseptic bone culture for diagnosing DFO. Receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic performance of ultrasonographic features. Sample size could not be determined as it is the first study to assess ultrasonographic features for the diagnosis of DFO. The research adhered to the guidelines for diagnostic accuracy studies (Standards for Reporting of Diagnostic Accuracy Studies [STARD] 2015). Results: All patients (n = 24) diagnosed with DFO exhibited positive power Doppler, resulting in a sensitivity (S) and specificity (SP) of 1 and an area under the curve (AUC) of 1 (p < 0.001 [1-1]). Cortical disruption was present in 23 patients (95.8%) with DFO, yielding an S of 0.93, SP of 1, and AUC of 0.96 (p < 0.001 [0.88-1]). Innovation: It validates the diagnostic value of US for DFO as it is the first and largest study of its kind to establish a clear reference standard to guide clinician decision-making. Conclusion: This study demonstrates the effectiveness of cortical disruption and positive power Doppler in assessing DFO through US.

A deeper look at low-frequency contact ultrasonic debridement in the clinical management of patients with diabetic foot ulcers.

The current study aimed to evaluate the dispersal of solution and microbes (aerosol) in the clinical environment during treatment with Low-frequency contact ultrasonic debridement (LFCUD) with or without suction attachment in patients with diabetic foot ulcers (DFUs). We performed 20 treatments in 10 patients divided into two groups to receive the proposed LFCUD modalities. We measured the microbial load of the environment pre-treatment (sample M1), during treatment with each LFCUD modality (sample M2) and post-treatment (sample M3). The use of LFCUD debridement without a suction attachment results in significantly higher immediate contamination of the clinic environment than the suction attachment, particularly during the procedure (1.70 ± 0.98 log 10 CFU/mL versus 0.77 ± 0.85 log 10 CFU/mL, p = 0.035). When suction is not applied, there are statistically significant differences depending on whether the DFUs are neuropathic or neuroischemic, finding a greater number of microorganisms with high loads in neuropathic DFUs. We found a statistically significant positive correlation between wound area (r = 0.450, p = 0.047) and TBI (r = 0.651, p = 0.006) with the bacterial load during the LFCUD. Based on our results, we recommend using the personal protective equipment required to protect staff members and patients during treatment with LFCUD and using a suction attachment where clinically possible to reduce clinic environmental pollution, especially in neuropathic DFUs and those with larger areas.

Effectiveness of Percutaneous Flexor Tenotomies for the Prevention and Management of Toe-Related Diabetic Foot Ulcers: A Systematic Review.

There is a high prevalence of digital deformities in diabetic patients, particularly claw toe, which can result in ulceration, often located at the tip of the toe. These lesions are challenging to off-load with conventional devices and frequently lead to infection and high amputation rates. Recent guidelines recommend considering flexor tenotomies to manage these ulcerations and prevent complications. This review, which analyzed 11 studies, aimed to assess the effect of flexor tenotomies on the healing and prevention of diabetic foot ulcers (DFUs) at the toe tip. Satisfactory results were found, with a healing rate of 92% to 100% and a mean healing time of 2-4 weeks. Few mild complications were observed, and the recurrence rate was very low. Transfer lesions were the most prevalent, but simultaneous tenotomy of all toes can eliminate this risk. Flexor tenotomies are a simple, effective, and safe procedure for the treatment and management of DFUs located at the apex of the toes and should be considered part of the standard of care for diabetic feet.

Culture Concordance in Different Sections of the Metatarsal Head: Interpretations of Microbiological Results.

Microbiological cultures of per-wound bone biopsies have shown a lack of correlation and a high rate of false-negative results when compared with bone biopsy cultures in diabetic foot osteomyelitis. The selection of samples from the area of active osteomyelitis, which contains a complete census of the microorganisms responsible for the infection, is essential to properly guide antimicrobial treatment. We aimed to comparatively evaluate the quantitative and qualitative cultures taken from different areas, in metatarsal heads resected for osteomyelitis. For this purpose, we consecutively selected 13 metatarsal heads from 12 outpatients with plantar ulcers admitted to our diabetic foot unit. Metatarsal heads were divided transversally into 3 portions: plantar (A), central (B), and dorsal (C), and the 39 resulting samples were cultured. Qualitative and quantitative microbiological analysis was performed, and the isolated species and bacterial load, total and species specific, were compared between the 3 metatarsal bone segments. The primary outcome of the study was the bacterial diversity detected in the different bone sections. Cultures were positive in 12 of the 13 included metatarsal heads (92%). A total of 34 organisms were isolated from all specimens. Ten of the 12 cultures (83%) were polymicrobial. Ten of the 13 metatarsal heads (77%) had identical microbiological results in each of the 3 bone sections. The largest number of microorganisms was found in the central section. The overall concordance between sections was 91%. The predominant microorganisms were coagulase-negative staphylococci (41%). Statistical differences were not found in the bioburden between sections (range 3.25-3.41 log10 colony-forming unit/g for all sections; P = .511). The results of our study suggest that microorganisms exhibit a high tendency to spread along the metatarsal bone and that the degree of progression along the bone is species dependent. The central portions of metatarsal bones tend to accumulate a higher diversity of species. Thus, we recommend this area of bone for targeted biopsy in patients with suspected osteomyelitis.

Clinical Efficacy of a 3D Foot Scanner app for the Fitting of Therapeutic Footwear in Persons with Diabetes in Remission: A Randomized and Controlled Clinical Trial.

To evaluate the ability of high-risk patients with diabetes in remission to select proper therapeutic footwear (TF) and validate a novel 3D foot scanner app for selecting the proper fitting TF. We conducted a randomized and controlled clinical trial enrolling 30 patients with a previously healed diabetic foot ulcer carried out in a specialized diabetic foot unit between November 2021 and June 2022. All patients were recommended to TF with extra depth volume and rocker sole. The control group could acquire the TF size and model according to aesthetic preferences, while the experimental group had to acquire a specific size and model according to the result of a novel mobile app 3D feet scan. TF was recommended to change when the ill-fitting reasons were found, excessive length or tightness or compromise with toes. The primary outcome measure was the requirement of TF change after prescription because of ill-fitting. A total of seven patients required TF change, one of them (6.7%) in the experimental group and six patients (40%) in the control group (p = .031, 95% CI [0.011-1.04]). Reasons for ill-fitting were as follows: four patients due to excessive length and three patients due to toe compromise. The relative risk reduction for the need to change the TF via the foot scan compared to the control group was 83%, and the number needed to treat was 20. High-risk patients with diabetes tend to select TF with inadequate fitting (length or capacity), and they should be guided hand to hand to acquire proper TF.

Effects of wear and tear of therapeutic footwear in patients remission. A 5-year follow-up study.

AIMS: To assesses the relationship between the wear and tear of therapeutic footwear (TF) and the risk of recurrence in diabetes remission patients. METHODS: Remission patients (N = 115) participated in this 5-year prospective study in a specialized Diabetic Foot Unit between October 2016 and January 2022. Patients' TF was assessed in a three-month interval from Day 0 until ulcer recurrence was found. Primary outcome measure was based on the recurrent event in the forefoot. RESULTS: A total of 82 patients (71.3%) renewed their TF, and 33 patients (28.7%) did not renew their TF during the follow-up period. Patients who failed to renew their TF group experienced more recurrent events (22 vs 14, p <.001, CI [0.04-0.259]) and minor amputations (11 vs 8, p =.002, CI [0.07-0.6]). Both groups showed different recurrence-free survival median times of 205.5 [Interquartile range (IQR) - 188-222] weeks and 89.9 [IQR - 53-126] weeks. Patients who did not renew their TF increased their risk of suffering from a recurrent event in the Cox regression model (p <.001, CI [0.03-0.38], Hazzard Ratio 0.147). CONCLUSIONS: Patients who renewed their TF because of wear and tear experienced lower recurrences and minor amputations.

Predictive value of forefoot plantar pressure to predict reulceration in patients at high risk.

AIMS: To analyze a plantar pressure cut-off point for diabetic foot reulceration beneath the metatarsal heads in patients with previous forefoot amputation. METHODS: A one-year prospective study was conducted in a total of 105 patients at high risk for foot ulceration. Peak plantar pressure (PPP) and pressure-time integral (PTI) in the entire foot, the forefoot region, and each metatarsal head separately were registered. ROC curves were used to select the optimal diagnostic pressure cut-off points. Patients were follow-up monthly or until the development of an ulcer event. RESULTS: A total of 52 (49.5%) patients developed a reulceration. Using ROC analyses for PPP in the full-foot and in the forefoot, did not predict reulceration beneath the metatarsal heads. Analyzing separately each metatarsal head all patients with values greater than or equal to 20.8 N/cm2 at the 1st, 18.62 N/cm2 for the 2nd, 18.85 at the 3rd, 17.88 at the 4th, and 12.2 at the 5th metatarsal heads will suffer a reulceration despite the use of orthopedic treatment with optimum values of sensitivity (from 100 to 87.5) and specificity (from 83.2 to 62.8). CONCLUSION: Barefoot pressures beneath the metatarsal heads should be analyzed separately to predict the region at risk of reulceration.

PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis.

The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.

Evaluation of the lung immune prognostic index in advanced non-small cell lung cancer patients under nivolumab monotherapy.

The lung immune prognostic index (LIPI) has been proposed as a new categorical blood-based biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 (PD-1) or programmed death ligand 1 (PD-L1) therapy. In this study, we investigate for the first time to the best of our knowledge the prognostic and predictive utility of the LIPI in a multicenter nivolumab monotherapy-based cohort. We retrospectively analyzed the influence of the baseline LIPI on overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR) among 153 patients of a cohort of 188 advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond. Worse LIPI was significantly associated with shorter OS in univariate [hazard ratio (HR) =3.12, 95% confidence interval (CI), 2.12-4.60; P<0.0001] and multivariate (HR =3.67, 95% CI, 1.96-6.86; P<0.0001) analyses. Worse LIPI was associated with shorter PFS (HR =1.45, 95% CI, 1.05-2.03; P=0.03), but this correlation did not reach statistical significance in multivariate analysis (HR =1.49, 95% CI, 0.94-2.38; P=0.09). Worse LIPI was associated with lower DCR in univariate [odds ratio (OR) =0.41, 95% CI, 0.24-0.70; P=0.001] and multivariate (OR =0.44, 95% CI, 0.25-0.78; P=0.005) analyses. This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.

Complications associated with the approach to metatarsal head resection in diabetic foot osteomyelitis.

The aim of this study was to evaluate the recovery time and the development of complications in the dorsal and plantar approach to metatarsal head resections (MHR) in patients with diabetic foot ulcers complicated by osteomyelitis. A retrospective study was carried out involving 108 patients who underwent MHRs for the treatment of diabetic foot osteomyelitis. Two cohorts were defined: dorsal approach with incision closed with sutures and plantar approach with ulcer healed using conservative treatment. The main outcomes were the weeks until healing and complications related to the approaches. Fifty-three patients (49.1%) underwent a plantar approach and 55 (50.9%) a dorsal approach. Both approaches rendered similar healing times. However, the patients undergoing a dorsal approach developed more post-surgical complications than patients treated through a plantar approach. The dorsal approach intervention was performed on smaller and shallower ulcers; however, more complications developed at follow up using this approach than through a plantar approach for MHR complicated with osteomyelitis.

Validation of an algorithm to predict reulceration in amputation patients with diabetes.

The aim of this article was to assess the ability to predict reulceration in people with diabetes and a history of minor amputation according to the formula proposed by Miller et al. A retrospective study was performed on 156 consecutive records of patients with a recent history of simple or multiple forefoot amputation. The sample was divided according to Miller's formula into patients at low risk of reulceration and those at high risk; those were further divided into two subgroups according to whether or not the first segment of the forefoot had been amputated. Forty-eight (47·1%) individuals suffered forefoot reulceration, showing a median reulceration-free survival time of 8 months [interquartile range (IR) 3·6-14·8]. Nephropathy (P = 0.005) and Miller's formula (P = 0.028) were risk factors for reulceration-free survival time in the univariate analysis. The pattern relating to the first segment amputated [hazard ratio (HR) 2·853; P = 0·004; 95% confidence interval (CI) 1·391-5·849] and nephropathy (HR 2·468; P = 0.004; 95% CI 1.328-4.587) showed a significant hazard ratio in the multivariate Cox model. Participants with first segment amputation and one other amputation showed an association with the probability of reulceration in comparison with any other specific type of minor amputation.

Fluorescence in situ hybridization analysis of the ALK gene in 2,045 non-small cell lung cancer patients from North-Western Spain (Galicia).

Identification of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is a standard diagnostic test in patients with advanced non-small cell lung cancer (NSCLC). The current study describes the experience of ALK rearrangement detection of a referral center in the public health care system of Galicia in North-Western Spain. The fluorescence in situ hybridization (FISH) patterns of the ALK gene and the clinical and pathological features of these patients are reported. This study is also of interest for comparative purposes due to the relative geographical isolation of the area, which could have contributed to particular genetic features. A total of 2,045 tissue samples from NSCLC patients were collected between October 2010 and July 2015 and tested for ALK rearrangements by FISH. Examination of 1,686 paraffin-embedded tissue specimens and 395 cytological samples (306 cell block preparations and 53 cytological smears) was conducted, and any associations between the FISH results and clinicopathological features were assessed. The rate of successful evaluation was marginally higher in tissue samples than in cytological samples (92.9% vs. 84.1%); this difference was not significant. ALK rearrangements were identified in 82 patients(4%): 65 (79.3%) in tissue specimens, 15 (18.3%) in cell block samples and 2 (2.4%) in cytological smears. This genetic translocation appeared to be associated with a non-smoking history, younger age, female gender, stage IV and adenocarcinoma histological type. The findings demonstrate that ALK evaluation by FISH is feasible in tissue and cytological samples. The clinical and pathological features of the ALK-positive series of patients are similar to those previously reported in the literature.

Impact on clinical practice of the implementation of guidelines for the toxicity management of targeted therapies in kidney cancer. The protect-2 study.

BACKGROUND: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. METHODS: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. RESULTS: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7% out of 966 post-implementation cycles compared with 23.1% out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33% pre-implementation vs. 44.5% post-implementation cycles; p < 0.0001), diarrhea (74.0% vs. 80.5%; p = 0.011) and dyslipemia (25.0% vs. 44.6%; p < 0.001). CONCLUSIONS: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction.

Interobserver and intraobserver reproducibility of plain X-rays in the diagnosis of diabetic foot osteomyelitis.

The purpose of this study was to analyze the interobserver and intraobserver variability in plain radiography in the diagnosis of diabetic foot osteomyelitis. A prospective observational study was performed from October 1, 2009, to July 31, 2011, on patients with diabetic foot ulcers, with clinically suspected osteomyelitis who were admitted to the Diabetic Foot Unit of the Complutense University of Madrid. Two professional groups examined 123 plain X-rays, each group comprising 3 different levels of clinical experience. To analyze intraobserver variability, 2 months later plain X-rays were reanalyzed by one of the clinical groups. When using only plain radiography for the diagnosis of osteomyelitis in the diabetic foot, low concordance rates were observed for clinicians with a similar level of experience: experienced clinicians (K(11AB) = .35, P < .001), moderately experienced clinicians (K(22AB) = .39, P < .001), and inexperienced clinicians (K(33AB) = .40, P < .001). Intraobserver agreement was highest in experienced clinicians (K(11A) = .75, P < .001), followed by moderately experienced clinicians (K(22A) = .61, P < .001) and inexperienced clinicians (K(33A) = .57, P < .001). Plain radiography for the diagnosis of diabetic foot osteomyelitis is operator dependent and shows low association strength, even among experienced clinicians, when interpreted in isolation without knowing the clinical characteristics of the lesion.

Molecular basis of hypertension side effects induced by sunitinib.

Over the past decade a number of vascular complications have emerged, such as newly developed or worsened hypertension, in patients who were administered with new cancer treatments for several types of cancer that were untreatable earlier. Hypertension is emerging as one of the most common adverse effects of therapy with angiogenesis inhibitors. Small-molecule inhibitors of vascular endothelial growth factor signalling are associated with a high proportion of patients with hypertension. The mechanisms underlying the development of hypertension are not well known, although there seem to be several mechanisms. Physiopathology of hypertension implicates abnormalities in endothelial function and angiogenesis. Several features of hypertensive patients are reduced number of arterioles and capillaries, alterations of the microvascular network, decrease in vascular wall compliance and flexibility, reduced nitric oxide bioactivity and increases in plasma vascular endothelial growth factor. Treatment with tyrosine kinase inhibitors (TKIs) is associated with a significant and sustained increase in blood pressure. We suspect that TKIs exert their hypertensive effects directly at the level of the microvascular network through processes such as vascular rarefaction, endothelial dysfunction and/or altered nitric oxide metabolism. This study shows the vascular complications of treatment with a TKI, sunitinib (SU11248), with special emphasis on hypertension.

Metástasis testicular de un adenocarcinoma de colon: reporte de un caso / Testicular matastases in colon adenocarcinoma: a case report

Reportamos el caso de un paciente con metástasis hepáticas, secundarias a adenocarcinoma de colon, quien presentaba una masa paratesticular dolorosa, cuya aparición coincidió con una progresión de la neoplasia de base. La resección quirúrgica de la masa identificó células neoplásicas provenientes del adenocarcinoma de colon.

We report the case of a patient with hepatic metastases secondary to colon adenocarcinoma. Who presented a par testicular and pain mass, which apparitions coincide with a progression of his basic neoplasic. The surgical resection of the mass identifies neoplásica cells with colon adenocarcinoma origin.