Immediate foot reconstruction and revascularization of toes using an interposition superficial circumflex iliac artery perforator flow-through flap: A case report.

Foot injuries, particularly degloving injuries, can lead to segmental loss of neurovascular structures in the toes, making simultaneous reconstruction of both the foot and toes challenging. This case report presents a technique using the superficial circumflex iliac artery perforator (SCIP) flap for immediate reconstruction of the dorsal foot and revascularization of multiple toes. A 28-year-old man suffered a degloving injury on the dorsum of his foot resulting in a 9 × 6cm skin defect, open fracture dislocations, exposure of tendons, and neurovascular injury, which included a 6-7.5 cm segmental defect of the vessels supplying the first, second, and third toes leaving all three toes ischemic. Immediate reconstruction was performed by harvesting a 12.5 × 5cm SCIP flap including both the superficial and deep branches and incorporating the superficial inferior epigastric vein (SIEV). The SCIP deep branch was used to revascularize the third and second toes and the SIEV vein graft used for the first toe. The patient recovered well, no complications were observed at the 2-year follow-up, preserving all three toes and regaining mobility. The use of the SCIP flap as a flow-through flap provides thin skin flap cover, good vessel caliber size match with digital vessels and reduces the need for vein grafts from distant sites improving surgical efficiency. These attributes make the flow-through interposition SCIP flap an excellent choice for reconstructing foot defects and revascularizing toes. We report this case to demonstrate the utility of the SCIP flap in immediate soft tissue cover and digit revascularization.

Temporal changes in toe-brachial index results in haemodialysis patients.

INTRODUCTION: Toe brachial index (TBI), the ratio of toe pressure to systolic blood pressure (SBP), helps predict peripheral arterial disease. In patients with kidney failure this may be performed during haemodialysis for convenience. Until recently there has been little evaluation of the impact of haemodialysis in limb and systemic perfusion on these values. We aimed to determine if the values of TBI would change during and after dialysis compared to pre-dialysis assessments. METHODS: Using a repeated measures study, TBIs and toe pressures were measured using the Hadeco Smartop Vascular Ultrasound Doppler in 31 patients undergoing haemodialysis. TBI assessments were completed pre-dialysis and compared to values obtained at 1 hour, 2 hours, 3 hours, and post-dialysis to monitor change in TBI results. Comparison of values for each patient were tested for differences using paired t-tests. Linear mixed-effects models were used to test for the effect of patient and clinical factors on change in outcome measures. RESULTS: Mean TBI decreased from pre-dialysis at 1 hour (0.72 to 0.63, p = 0.01) and remained lower at 2 hours and 3 hours, before returning to pre-dialysis levels at post-dialysis. Mean systolic blood pressure also declined during dialysis. Mean TBI results were lower in those with a history of lower limb ulceration and in females. Sixteen patients (51.6%) had a normal TBI at baseline, 14 (45.2%) had a mildly low TBI, and one (3.2%) had a severely low TBI. Between baseline and 1 h, five patient's results moved from normal to mildly abnormal and one from mildly abnormal to severely abnormal. As haemodialysis concluded (post-dialysis) there were 17 (56.7%) 'normal' TBIs, with no severely abnormal TBIs (p = 0.73). 0.30). CONCLUSION: TBI and toe pressures are impacted significantly by dialysis. TBI and toe pressure assessments should be conducted before haemodialysis begins, or between dialysis sessions to avoid variability.

Non-contrast MRI of micro-vascularity of the feet and toes.

PURPOSE: This study aimed to develop novel non-contrast MR perfusion techniques for assessing micro-vascularity of the foot in human subjects. METHODS: All experiments were performed on a clinical 3 T scanner using arterial spin labeling (ASL). Seven healthy subjects (30-72 years old, 5 males and 2 females) were enrolled and bilateral feet were imaged with tag-on and tag-off alternating inversion recovery spin labeling for determining micro-vascularity. We compared an ASL technique with 1-tag against 4-tag pulses. For perfusion, we determined signal increase ratio (SIR) at varying inversion times (TI) from 0.5 to 2 s. SIR versus TI data were fit to determine perfusion metrics of peak height (PH), time to peak (TTP), full width at half maximum (FWHM), area under the curve (AUC), and apparent blood flow (aBF) in the distal foot and individual toes. Using analysis of variance (ANOVA), effects of tag pulse and region of interest (ROI) on the mean perfusion metrics were assessed. In addition, a 4-tag pulse perfusion experiment was performed on patients with peripheral artery disease (PAD) and Raynaud's disease. RESULTS: Using our MR perfusion techniques, SIR versus TI data showed well-defined leading and trailing edges, with a peak near TI of 0.75-1.0 s and subsiding quickly to near zero by TI of 2 s, particularly when 4-tag pulses were used. When imaged with 4-tag pulse, we found significantly greater values in perfusion metrics, as compared to 1-tag pulse. The patients with PAD and Raynaud's disease showed a reduced or scattered perfusion curves compared to the healthy control. CONCLUSION: MR perfusion imaging of the distal foot shows greater SIR and perfusion metrics with the 4-tag pulse compared to the 1-tag pulse technique. This will likely benefit those with low perfusion due to aging, PAD, diabetic foot, and other vascular diseases.

A new method for second toe flap revascularization in plantar dominant artery pattern - dorsal metatarsal artery interpositional graf.

BACKGROUND: Toe transfer to hand is a viable option for patients, which can provide functionally useful digits. Harvesting of the second toe is still accepted as a demanding surgical procedure. The major questions before this transfer are the location and the dominance of the arterial anatomy of the second toe. The authors present the incidence of patients with a dominant plantar artery system and a description of a versatile technique that can be used for toe transfers in these patients. METHODS: The study was designed retrospectively. Toe to hand transfers performed between 2010 and 2018 were reviewed. The patients with a dominant plantar arterial system were included in this study. The dorsalis pedis arterial graft technique described by the authors was used in all cases with a dominant plantar system. All of transfers were done by the senior author. All cases followed up at least one year post-operatively. The survival of the transferred finger was examined in the follow-ups. RESULTS: Eleven toe to hand transplantation cases in nine traumatic patients were included in this series. The reason for the operation was trauma in all patients. Second toe transfer was performed in all of the cases. Plantar dominant arterial system was seen in 3 of the 9 patients. Dorsal arterial system was dominant in the remaining six patients. Dorsalis pedis arterial graft technique was used in these four cases. All of the toes survived, and reexploration was needed in 2 cases because of venous insufficiency. Mean follow-up time was 16.4 months. DISCUSSION: This is the first study to recommend the use of dorsalis pedis as an arterial graft instead of vein grafts. This surgical method described will make these rarely performed transfers easier and affect the success rates positively.

Vascular Assessment in Patients With a Lower Limb Wound: A Correlational Study of Photoplethysmography and Laser Doppler Flowmetry Toe Pressure Techniques.

BACKGROUND: Vascular assessment of the lower limbs is essential in patients with diabetes. In the presence of noncompressible arteries, the ankle brachial index (ABI) can either be inconclusive or provide false-positive results. Toe pressure measurement has been suggested as an alternative as a noninvasive method for detecting peripheral arterial disease (PAD). Toe pressure measurement can be performed either by photoplethysmography (PPG) or by Laser Doppler flowmetry (LDF). The aim of this study was to determine correlations between the two techniques in order to promote the use of PPG in clinical practice. METHODS: This was a prospective correlational study of 108 consecutive recruited adult patients, with and without diabetes, with at least one lower limb wound from a University-affiliated hospital wound care clinic. Toe pressure measurements were both performed with PPG and LDF devices. RESULTS: Mean toe pressure values for PPG and LDF were, respectively, 83.7 (SD 35.4) and 79.5 (SD 32.0) mmHg (with a paired t-test 3.969, P < 0.01). In patients with at least one lower limb wound, a strong linear relation was found between PPG and LDF toe pressure techniques with a Pearson's r correlation coefficient of 0.920 (P < 0.001). CONCLUSIONS: PPG and LDF toe pressure techniques are equivalent in patients with at least one lower limb wound, irrespective of the presence of diabetes. Therefore, in the presence of an ABI with inconclusive results, such as in a patient with noncompressible vessels, both toe pressure techniques can be used for assessing the vascular supply of the lower limb with a wound.

Stimulation TcPO2 Testing Improves Diagnosis of Peripheral Arterial Disease in Patients With Diabetic Foot.

Background: All diagnostic procedures of peripheral arterial disease (PAD) in diabetic foot (DF) are complicated due to diabetes mellitus and its late complications.The aim of our study is to enhance diagnosis of PAD using a novel transcutaneous oximetry (TcPO2) stimulation test. Methods: The study comprised patients with mild-to-moderate PAD(WIfI-I 1 or 2) and baseline TcPO2 values of 30-50 mmHg.TcPO2 was measured across 107 different angiosomes. Stimulation examination involved a modification of the Ratschow test. All patients underwent PAD assessment (systolic blood pressures (SBP), toe pressures (TP), the ankle-brachial indexes (ABI) and toe-brachial indexes (TBI), duplex ultrasound of circulation). Angiosomes were divided into two groups based on ultrasound findings: group M(n=60) with monophasic flow; group T(n=47) with triphasic flow. Large vessel parameters and TcPO2 at rest and after exercise (minimal TcPO2, changes in TcPO2 from baseline (Δ,%), TcPO2 recovery time) measured during the stimulation test were compared between study groups. Results: During the TcPO2 stimulation exercise test, group M exhibited significantly lower minimal TcPO2 (26.2 ± 11.1 vs. 31.4 ± 9.4 mmHg; p<0.01), greater Δ and percentage decreases from resting TcPO2 (p=0.014 and p=0.007, respectively) and longer TcPO2 recovery times (446 ± 134 vs. 370 ± 81ms;p=0.0005) compared to group T. SBPs, TPs and indexes were significantly lower in group M compared to group T. Sensitivity and specificity of TcPO2 stimulation parameters during PAD detection increased significantly to the level of SBP, ABI, TP and TBI. Conclusion: Compared to resting TcPO2, TcPO2 measured during stimulation improves detection of latent forms of PAD and restenosis/obliterations of previously treated arteries in diabetic foot patients. Clinical Trial Registration: ClinicalTrials.gov [https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009V7W&selectaction=Edit&uid=U0005381&ts=2&cx=3j24u2], identifier NCT04404699.

Association between preoperative toe perfusion index and maternal core temperature decrease during cesarean delivery under spinal anesthesia: a prospective cohort study.

BACKGROUND: The main mechanism of body temperature decrease during cesarean delivery under spinal anesthesia is core-to-peripheral redistribution of body heat, attributable to vasodilation. Perfusion index (PI) obtained with a pulse oximeter helps to assess peripheral perfusion dynamics by detecting the change in peripheral vascular tone. This study aimed to examine whether preoperative toe PI could predict the decrease in core temperature induced by spinal anesthesia during cesarean delivery. METHODS: Parturients undergoing scheduled cesarean delivery under combined spinal-epidural anesthesia from September 2019 to March 2020 were enrolled in this single-center prospective cohort study. All parturients received 0.5% hyperbaric bupivacaine (10 mg) with fentanyl (15 µg) intrathecally. A pulse oximeter probe was placed on the left second toe for continuous PI measurement. The 3 M™ Bair Hugger™ Temperature Monitoring System placed over the right temporal region was used to record core temperature over time. We evaluated the association between the maximum core temperature decrease, which is the primary outcome, and the preoperative toe PI at operating room (OR) admission using a segmented regression model (SRM) and a generalized additive model (GAM). The maximum core temperature decrease was defined as the difference between core temperature at OR admission and minimum intraoperative core temperature. RESULTS: Forty-eight patients were evaluated. In the SRM, the slope for the association between the maximum core temperature decrease and the preoperative toe PI changed from 0.031 to 0.124 after PI = 2.4%. Likewise, with the GAM, there was a small core temperature decrease when preoperative toe PI was greater than 2.0 to 3.0%. CONCLUSIONS: Low preoperative toe PI was associated with maternal core temperature decrease during cesarean delivery under spinal anesthesia. Preoperative toe PI is a simple, non-invasive, and effective tool for the early prediction of perioperative core temperature decrease during cesarean delivery. TRIAL REGISTRATION: UMIN Clinical Trials Registry (registry number: UMIN000037965 ).

Accuracy of Ankle-Brachial Index, Toe-Brachial Index, and Risk Classification Score in Discriminating Peripheral Artery Disease in Patients With Chronic Kidney Disease.

The accuracy of ankle-brachial index (ABI) and toe-brachial index (TBI) in discriminating lower extremity peripheral artery disease (PAD) has not been evaluated in patients with chronic kidney disease (CKD). We measured ABI, TBI, and Doppler ultrasound in 100 predialysis patients with CKD without revascularization or amputation. Leg-specific ABI was calculated using higher systolic blood pressure (SBP) in posterior tibial or dorsalis pedis artery divided by higher brachial SBP; alternative ABI was calculated using lower SBP in posterior tibial or dorsalis pedis artery. PAD was defined as ≥50% stenosis detected by Doppler ultrasound. PAD risk classification score was calculated using cardiovascular disease risk factors. The area under the curve (AUC, 95% confidence interval [CI]) for discriminating ultrasound-diagnosed PAD was 0.78 (0.69 to 0.87) by ABI, 0.80 (0.71 to 0.89) by alternative ABI, and 0.74 (0.63 to 0.86) by TBI. Sensitivity and specificity were 25% and 97% for ABI ≤0.9, 41% and 95% for alternative ABI ≤0.9, and 45% and 93% for TBI ≤0.7, respectively. AUC (95% CI) of PAD risk classification score was 0.86 (0.78 to 0.94) with sensitivity and specificity of 95% and 60% for risk score ≥0.10, 76% and 76% for risk score ≥0.25, and 43% and 95% for risk score ≥0.55. Combining risk score with ABI, alternative ABI, and TBI increased AUC (95% CI) to 0.89 (0.82 to 0.96), 0.89 (0.80 to 0.98), and 0.87 (0.78 to 0.96), respectively. In conclusion, current ABI and TBI diagnostic criteria have high specificity but low sensitivity for classifying PAD in patients with CKD. PAD classification risk score based on cardiovascular disease risk factors improves the accuracy of PAD classification.

Intraprocedural Transcutaneous Oxygen Pressure and Systolic Toe Pressure Measurements During and After Endovascular Intervention in Patients with Chronic Limb Threatening Ischaemia.

OBJECTIVE: The aim of this study was to evaluate changes in transcutaneous oxygen pressure (tcpO2) and systolic toe pressure (TP) during endovascular intervention. METHODS: This was a single centre prospective, non-randomised, observational feasibility study. Patients with chronic limb threatening ischaemia (CLTI) due to infrainguinal disease scheduled for endovascular treatment were included between March 2018 and December 2019. TcpO2 was measured continuously bilaterally at foot level throughout the procedure and at follow up. Specific time points during the intervention were chosen for comparison to baseline (before arterial puncture): average tcpO2 level five minutes prior to percutaneous transluminal angioplasty (PTA); 10 minutes after PTA; and at completion. Bilateral TP was recorded using laser Doppler flowmetry before arterial puncture, at completion, and at clinical follow up. Angiograms were analysed for successful revascularisation and vascular lesions classified according to the Global Limb Anatomical Scoring System (GLASS). Rutherford and WIfI (Wound, Ischaemia, and foot Infection) classifications were registered, as well as clinical outcome. RESULTS: Twenty-one patients completed the study. Completion angiograms showed inline flow to the foot in all but two patients. Median time to follow up was 10 weeks (range 8 - 13 weeks) and all patients except one improved clinically. TcpO2 decreased during the initial stage of the intervention, from before arterial puncture to five minute average before PTA (p < .001) and did not recover to above baseline values at the end of intervention. TcpO2 increased significantly at follow up (p < .001). TP increased statistically significantly during intervention (p < .001) and at follow up (p < .001) compared with baseline. CONCLUSION: TcpO2 and TP measurements are safe and feasible non-invasive techniques for haemodynamic monitoring during endovascular revascularisation. TP increased significantly immediately after completion of the successful intervention, whereas tcpO2 did not. Both TP and tcpO2 demonstrated a significant increase at the 10 week follow up.

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia.

BACKGROUND: H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. CASE PRESENTATION: 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. CONCLUSIONS: We report the most severe disease course produced by HS described so far in the literature. Our patient's manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.

Using 320-detector row computed tomography angiography to investigate the arterial anatomy of the toe flaps on living humans.

PURPOSE: Using 320-detector row computed tomography angiography (320-CTA) to investigate the arterial supply for the toe flaps, namely the anatomical characteristics of the dorsalis pedis artery (DPA), the first dorsal metatarsal artery (FDMA), and the arteries of the first toe web space (AsFTWS). METHODS: This was a prospective study on CTA of 72 intact feet of 36 Vietnamese adults who had sequelae of thumb or metacarpal hand amputation, from June 2017 to December 2019, then preoperative CTA images were compared with surgical findings on 31 feet of 29 patients. RESULTS: 320-CTA was able to investigate the DPA, FDMA, and AsFTWS in 100% of cases. DPA was absent in 6.9% of cases. The average diameters at its origin and termination were 3.22 and 2.56 mm, respectively. For FDMA, the rates of Gilbert type I, II, and III were 52.8%, 18.1%, and 29.2%; the average diameters at its origin and termination were 1.98 and 1.67 mm, respectively. At the first toe web space, FDMA was dominant in 54.2% of cases; the first plantar metatarsal artery (FPMA) was dominant in 29.2% of cases; both arteries were equally dominant in 16.6%. The average diameter at the origin of the lateral plantar digital artery of the great toe was 1.48 mm, of the medial plantar digital artery of the second toe was 1.21 mm. Preoperative CTA images resembled the surgical findings in all cases. The survival rate of toe flaps was 100%. CONCLUSION: The 320-CTA provided proper preoperative images in two and three dimensions, and helped surgeons to establish a preoperative surgical plan, thus increasing the success rate of toe transfer surgery.

Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic.

Importance: Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. Objective: To examine the association of chilblain-like lesions with SARS-CoV-2 infection. Design, Setting, and Participants: This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. Main Outcomes and Measures: Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. Results: Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. Conclusions and Relevance: This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms.

Chilblain-Like Lesions (CLL) Associated With COVID-19 ("COVID Toes"): A Systematic Review.

Reports of chilblain-like lesions (CLL) coinciding with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described in the literature, but this phenomenon has not been critically summarized. The aim of this paper is to summarize reports of CLL coinciding with SARS-CoV-2 infection to clarify the prevalence, clinical relevance, and prognostic value of these lesions. A literature search was conducted using the Embase, Pubmed, and Scopus databases from December 2019 to June 16, 2020 using the search terms ("COVID-19" OR "coronavirus" OR "2019-nCoV" OR "SARS-CoV-2") AND ("chilblain-like" OR "COVID toes" OR "acral"). Papers that described skin changes in patients with suspected or confirmed COVID-19 were included. A total of 31 papers were summarized, representing 813 cases of CLL. Available data suggests an equal gender distribution, mean age of 21 years, and median age of 14 years. Mild extracutaneous symptoms were reported in 53% of cases and 47% were asymptomatic. CLL occurred an average of 16 days after extracutaneous symptoms. Patients with CLL were positive for SARS-CoV-2 in 15% of cases. Lesions were mainly described as asymptomatic and/or pruritic erythematous to violaceous acral macules and plaques. Partial or complete resolution occurred in 85% of cases in a mean of 13 days. The most common histologic findings were perivascular and perieccrine superficial and deep lymphocytic infiltrates. Although a causal relationship between CLL and SARS-CoV-2 has not been confirmed, the temporal association and 15% positive SARS-CoV-2 rate in affected individuals should not be ignored.

Using human umbilical cord mesenchymal stem cells combined with allogenic platelet-rich fibrin membrane for the treatment of dual limb ischemia in an elderly patient: A case report.

RATIONALE: To describe the clinical effects of human umbilical cord mesenchymal stem cells (UCMSCs) combined with allogenic platelet-rich fibrin (PRF) for the treatment of lower limb ischemia in an elderly patient. PATIENT CONCERNS: The patient was a 93-year-old Chinese woman with bilateral foot gangrene and ulcers lasting for 6 months. She had a prior history of Behcet's disease. DIAGNOSES: The admitting diagnosis for this episode was atherosclerosis bilateral limb ischemia. INTERVENTIONS: First, treatment consisting of immunosuppressants, anticoagulation, antiplatelets, and anti-microbials were instituted. A UCMSC suspension was administered intravenously and injected into the lower limbs twice. An allogenic PRF membrane was externally applied 15 times over the lower limbs. OUTCOMES: The patient's pain improved and the 6 ulcers healed. LESSONS: The combination of UCMSCs with a PRF membrane for the treatment of lower limb ischemia in an elderly patient is effective and safe. More and larger trials are needed before incorporating this therapy into mainstream treatment.

Pernio (Chilblains), SARS-CoV-2, and COVID Toes Unified Through Cutaneous and Systemic Mechanisms.

Pernio or chilblains is characterized by erythema and swelling at acral sites (eg, toes and fingers), typically triggered by cold exposure. Clinical and histopathologic features of pernio are well described, but the pathogenesis is not entirely understood; vasospasm and a type I interferon (IFN-I) immune response are likely involved. During the coronavirus disease 2019 (COVID-19) pandemic, dermatologists have observed an increase in pernio-like acral eruptions. Direct causality of pernio due to COVID-19 has not been established in many cases because of inconsistent testing methods (often negative results) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a form of COVID-19‒associated pernio (also called COVID toes) is probable because of increased occurrence, frequently in young patients with no cold exposure or a history of pernio, and reports of skin biopsies with positive SARS-CoV-2 immunohistochemistry. PubMed was searched between January 1, 2020, and December 31, 2020 for publications using the following keywords: pernio, chilblain, and acral COVID-19. On the basis of our review of the published literature, we speculate that several unifying cutaneous and systemic mechanisms may explain COVID-19‒associated pernio: (1) SARS-CoV-2 cell infection occurs through the cellular receptor angiotensin-converting enzyme 2 mediated by transmembrane protease serine 2, subsequently affecting the renin-angiotensin-aldosterone system with an increase in the vasoconstricting, pro-inflammatory, and prothrombotic angiotensin II pathway. (2) Severe acute respiratory syndrome coronavirus 2 cell infection triggers an immune response with robust IFN-I release in patients predisposed to COVID-19‒associated pernio. (3) Age and sex discrepancies correlated with COVID-19 severity and manifestations, including pernio as a sign of mild disease, are likely explained by age-related immune and vascular differences influenced by sex hormones and genetics, which affect susceptibility to viral cellular infection, the renin-angiotensin-aldosterone system balance, and the IFN-I response.

Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus.

OBJECTIVE: Hydroxychloroquine (HCQ) has a primary role in the prophylaxis and treatment of systemic lupus erythematosus (SLE) and may be protective against thrombosis in SLE. Optimal weight-based dosing of HCQ is unknown. This study was undertaken to examine the usefulness of HCQ blood monitoring in predicting thrombosis risk in a longitudinal SLE cohort. METHODS: HCQ levels were serially quantified from EDTA whole blood by liquid chromatography-tandem mass spectrometry. The mean HCQ blood levels calculated prior to thrombosis or until the last visit were compared using t-tests between patients with and those without thrombosis. Pooled logistic regression was used to analyze the association between rates of thrombosis and HCQ blood level. Rate ratios (RRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: In 739 patients with SLE, thrombosis occurred in 38 patients (5.1%). The mean ± SD HCQ blood level was lower in patients who developed thrombosis versus those who did not develop thrombosis (720 ± 489 ng/ml versus 935 ± 580 ng/ml; P = 0.025). Thrombosis rates were reduced by 13% for every 200-ng/ml increase in the most recent HCQ blood level (RR 0.87 [95% CI 0.78-0.98], P = 0.025) and by 13% for mean HCQ blood level (RR 0.87 [95% CI 0.76-1.00], P = 0.056). Thrombotic events were reduced by 69% in patients with mean HCQ blood levels ≥1,068 ng/ml versus those with levels <648 ng/ml (RR 0.31 [95% CI 0.11-0.86], P = 0.024). This remained significant after adjustment for confounders (RR 0.34 [95% CI 0.12-0.94], P = 0.037). CONCLUSION: Low HCQ blood levels are associated with thrombotic events in SLE. Longitudinal measurement of HCQ levels may allow for personalized HCQ dosing strategies. Recommendations for empirical dose reduction may reduce or eliminate the benefits of HCQ in this high-risk population.

Toe pressure should be part of a vascular surgeon's first-line investigation in the assessment of lower extremity artery disease and cardiovascular risk of a patient.

OBJECTIVE: Toe pressure (TP) is an accurate indicator of the peripheral vascular status of a patient and thus cardiovascular risk, with less susceptibility to errors than ankle-brachial index (ABI). This study aimed to analyze how ABI and TP measurements associate with overall survival and cardiovascular death and to analyze the TP of patients with ABI of 0.9 to 1.3. METHODS: The first ABI and TP measurements of a consecutive 6784 patients treated at the Helsinki University Hospital vascular surgery clinic between 1990 and 2009 were analyzed. Helsinki University Vascular Registry and the national Cause of Death Registry provided the data. RESULTS: The poorest survival was in patients with ABI >1.3 (10-year survival, 15.3%; hazard ratio, 2.2; 95% confidence interval, 1.9-2.6; P < .0001; reference group, ABI 0.9-1.3), followed by the patients with TP <30 mm Hg (10-year survival, 19.6%; hazard ratio, 2.0; 95% confidence interval, 1.7-2.2; P < .0001; reference group, TP ≥80 mm Hg). The best 10-year survival was in patients with TP ≥80 mm Hg (43.9%). Of the 642 patients with normal ABI (0.9-1.3), 18.7% had a TP <50 mm Hg. The highest cardiovascular death rate (64.6%) was in the patients with TP <30 mm Hg, and it was significantly lower than for the patients with TP >50 mm Hg. CONCLUSIONS: Low TP is associated significantly with survival and cardiovascular mortality. Patients with a normal ABI may have lower extremity artery disease (LEAD) and a considerable risk for a cardiovascular event. If only the ABI is measured in addition to clinical examination, a substantial proportion of patients may be left without LEAD diagnosis or adequate treatment of cardiovascular risk factors. Thus, especially if ABI is normal, LEAD is excluded only if TPs are also measured and are normal.

An Autopsy Review: "COVID Toes".

ABSTRACT: "Severe acute respiratory syndrome coronavirus-2" (SARS-CoV-2) infection has variable described dermatologic manifestations. "COVID (coronavirus disease) toes" became a hallmark of the disease in young and largely asymptomatic patients, who may have negative test results for SARS-CoV-2. Pernio (chilblains)-like lesions are seen mostly in infected pediatric patients and are purple painful, frequently bilateral, ill-defined plaques with prominent inflammation on histological examination. In contrast to pernio-like presentation in children, critically ill adult patients with SARS-CoV-2 develop "purple" digits that may be sharply demarcated and may demonstrate asymmetric areas of ischemia. These 2 contrasting entities are sometimes grouped together as "COVID toes" due to some similarities in clinical appearance and presentation. Here, we summarize histopathologic examination from an autopsy, including the cutaneous lesions from the affected and normal contralateral toes and correlate them with systemic findings. In contrast to pernio-like lesions, the skin of the affected necrotic toes contained thrombi in vessels without prominent inflammation, suggestive of an embolic event. This is further supported by the clinical history of and autopsy findings of popliteal artery thrombus and multiple subsegmental pulmonary emboli. Our findings suggest that critically ill patients with SARS-CoV-2 have different pathological processes affecting skin at peripheral sites (ie, fingers, toes, ears, and nose), which may be due to thromboembolic events. The skin is a mirror of the body and skin pathology may shed light into overall pathogenesis of systemic illness and processes.

[Cutaneous Manifestations Associated with COVID-19: A Narrative Review]. / Manifestações Cutâneas Associadas à COVID-19: Uma Revisão Narrativa.

INTRODUCTION: COVID-19 is an infectious disease caused by the new coronavirus, SARS-CoV-2, that has spread rapidly throughout the world. This has resulted in an urgent need to obtain information regarding its pathogenesis, diagnosis and clinical manifestations. More specifically, skin manifestations, seldom reported initially, have been increasingly described. MATERIAL AND METHODS: We performed a literature search in the PubMed database, regarding cutaneous manifestations associated with COVID-19. This article describes the clinical and histological findings of the main skin lesions observed in the context of SARS-CoV-2 infection. DISCUSSION: Cutaneous manifestations associated with COVID-19 have been described in multiple retrospective and prospective studies, case series and case reports. The reported incidence reached 20.4%. Although there was substantial heterogeneity in terms of clinical patterns, the main ones include: erythematous/maculopapular, urticarial, papulovesicular, and purpuric/petechial eruptions, chilblain-like lesions and livedoid/acro-ischemic lesions. In the vast majority, the underlying pathophysiologic mechanisms are not fully understood, although histopathological findings and biomolecular studies can add relevant data. CONCLUSION: The recognition of cutaneous manifestations associated with COVID-19 is of utmost importance. They may help establishing an early diagnosis, namely in oligosymptomatic patients or when confirmatory tests are impossible to perform. Moreover, chilblain-like lesions and acro-ischemia, also seem to play an important role in terms of prognosis.

Introdução: A COVID-19, doença infeciosa causada por um novo coronavírus, SARS-CoV-2, propagou-se rapidamente pelo mundo inteiro, resultando numa necessidade emergente de obtenção de conhecimentos alusivos à sua patogénese, diagnóstico e sintomatologia. Mais especificamente, um número cada vez maior de casos relativos a manifestações cutâneas, previamente desconhecidas, tem vindo a ser descrito.Material e Métodos: Foi realizada uma pesquisa de literatura, através da base de dados PubMed, referente às manifestações dermatológicas associadas à COVID-19. O presente artigo descreve os achados clínicos e histológicos das principais lesões cutâneas observadas em contexto da infeção por SARS-CoV-2.Discussão: Manifestações cutâneas associadas à COVID-19 foram descritas em múltiplos estudos retrospetivos e prospetivos, séries de casos e casos clínicos isolados. A incidência reportada atingiu os 20,4%, verificando-se uma heterogeneidade de padrões clínicos substancial. Destes destacam-se as erupções eritematosas/maculopapulares, urticariformes, papulovesiculares, purpúricas/petequiais, lesões tipo-perniose e lesões livedóides/acro-isquémicas. O conhecimento dos mecanismos fisiopatológicos subjacentes tem vindo a ser enriquecido com achados os histológicos e de biologia molecular.Conclusão: É essencial o reconhecimento das manifestações dermatológicas associadas à COVID-19, uma vez que podem permitir o diagnóstico precoce da infeção, nomeadamente em casos oligossintomáticos ou quando não é possível a realização de testes confirmatórios. Embora menos estabelecido, lesões tipo-perniose e acro-isquémicas, parecem ter também um papel importante a nível prognóstico.

A 47-Year-Old Hispanic Man Who Developed Cutaneous Vasculitic Lesions and Gangrene of the Toes Following Admission to Hospital with COVID-19 Pneumonia.

BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in late 2019 and has led to an ongoing pandemic. COVID-19 typically affects the respiratory tract and mucous membranes, leading to pathological involvement of various organ systems. Although patients usually present with fever, cough, and fatigue, less common manifestations have been reported including symptoms arising from thrombosis and thromboembolism. A spectrum of dermatologic changes is becoming recognized in patients with COVID-19 who initially present with respiratory symptoms. The mechanism behind these manifestations remains unclear. This report presents the case of a 47-year-old Hispanic man who developed cutaneous vasculitic lesions and gangrene of the toes following admission to hospital with COVID-19 pneumonia. CASE REPORT COVID-19 has been associated with cardiovascular disease entities including stroke, acute coronary syndrome, venous thromboembolism, and peripheral vascular disease. We present a case in which a 47-year-old Hispanic man arrived at the Emergency Department with COVID-19 and was admitted for respiratory failure. Despite anticoagulation initiated on admission in the presence of an elevated D-dimer, the patient developed gangrene of all his toes, which required bilateral transmetatarsal amputation. CONCLUSIONS This case shows that dermatologic manifestations may develop in patients who initially present with COVID-19 pneumonia. These symptoms may be due to venous thrombosis following SARS-CoV-2 vasculitis, leading to challenging decisions regarding anticoagulation therapy. Randomized controlled trials are needed to evaluate the efficacy of anticoagulation, to choose appropriate anticoagulants and dosing, and to assess bleeding risk.