Effects of time to treatment initiation on outcomes for soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Few studies have investigated the effects of time to treatment initiation (TTI) for soft tissue sarcomas (STS). Our objective was to investigate the risk factors for prolonged TTI and the effects of prolonged TTI on local recurrence free survival (LRFS), distant metastasis free survival (DMFS), and disease specific survival (DSS). METHOD: Patients diagnosed with high-grade STS of the extremities and trunk from 2011 to 2020 were included. TTI was grouped into two groups (treatment provided in less than vs. more than or equal to 30 days). Two-year and 5-year survival probabilities were calculated for LRFS, DMFS, and DSS. Cox regression and Kruskal-Wallis tests in univariate analysis were conducted to find risk factors affecting TTI and the survival outcomes. RESULTS: In the univariate analysis, diagnosis in the later 5-year period of the study, tumor size, and treatment modality were associated with prolonged TTI. TTI ≥30 days was associated with higher DMFS but no association was found with LRFS or DSS. Tumor size, surgical margins, and provision of surgery were associated with DSS. CONCLUSION: Despite the delay in treatment for STS patients caused by the COVID-19 pandemic, our study showed TTI of more than 30 days does not negatively impact patients.

Acrodermatitis continua of Hallopeau: historical perspectives and modern management.

Acrodermatitis continua of Hallopeau is a sterile pustular dermatosis primarily of the digits. Often considered a type of pustular psoriasis, it may be difficult to diagnose and even more difficult to treat. Initial involvement of a distal finger or toe may appear as erythema which should not be confused with the chilblains-like findings potentially associated with COVID-19 infection. We review the clinical manifestations of and explore potential therapeutic options for this uncommon, clinically striking dermatosis.

Evaluation of Muscle Mass and Stiffness with Limb Ultrasound in COVID-19 Survivors.

BACKGROUND: acute illnesses, like COVID-19, can act as a catabolic stimulus on muscles. So far, no study has evaluated muscle mass and quality through limb ultrasound in post-COVID-19 patients. METHODS: cross sectional observational study, including patients seen one month after hospital discharge for SARS-CoV-2 pneumonia. The patients underwent a multidimensional evaluation. Moreover, we performed dominant medial gastrocnemius ultrasound (US) to characterize their muscle mass and quality. RESULTS: two hundred fifty-nine individuals (median age 67, 59.8% males) were included in the study. COVID-19 survivors with reduced muscle strength had a lower muscle US thickness (1.6 versus 1.73 cm, p =0.02) and a higher muscle stiffness (87 versus 76.3, p = 0.004) compared to patients with normal muscle strength. Also, patients with reduced Short Physical Performance Battery (SPPB) scores had a lower muscle US thickness (1.3 versus 1.71 cm, p = 0.01) and a higher muscle stiffness (104.9 versus 81.07, p = 0.04) compared to individuals with normal SPPB scores. The finding of increased muscle stiffness was also confirmed in patients with a pathological value (≥ 4) at the sarcopenia screening tool SARC-F (103.0 versus 79.55, p < 0.001). Muscle stiffness emerged as a significant predictor of probable sarcopenia (adjusted OR 1.02, 95% C.I. 1.002 - 1.04, p = 0.03). The optimal ultrasound cut-offs for probable sarcopenia were 1.51 cm for muscle thickness (p= 0.017) and 73.95 for muscle stiffness (p = 0.004). DISCUSSION: we described muscle ultrasound characteristics in post COVID-19 patients. Muscle ultrasound could be an innovative tool to assess muscle mass and quality in this population. Our preliminary findings need to be confirmed by future studies comparing muscle ultrasound with already validated techniques for measuring muscle mass and quality.

Vascular findings in CTA body and extremity of critically ill COVID-19 patients: commonly encountered vascular complications with review of literature.

The purpose of our review is to discuss the role of CT angiography (CTA) in evaluating a variety of vascular complications in critically ill COVID-19 patients. The COVID-19 pandemic continues to be a worldwide health threat. While COVID-19 pneumonia is the most common and well-recognized presentation of COVID-19, severely ill hospitalized patients often present with extrapulmonary systemic findings. Vascular complications occur not only due to known viral-induced vasculopathy, coagulopathy, and related "cytokine storm," but also due to anticoagulation medication used during hospitalization. There is a paucity of articles describing extrapulmonary vascular findings, especially in critically ill COVID-19 patients. In our article, we discuss commonly encountered vascular imaging findings in the body (chest, abdomen, and pelvis) and extremities, the importance of early radiological detection, and the role of CTA in the management of critically ill COVID-19 patients.

Ultrasound Evaluation for Extremity Deep Vein Thrombus in COVID-19-Positive Patients: Exam Positivity Rate and Association With D-Dimer Level.

OBJECTIVES: Determine the rate of positive extremity ultrasound exams for DVT in patients with COVID-19 and assess for differences in laboratory values in patients with and without DVT, which could be used as a surrogate to decide the need for further evaluation with ultrasound. METHODS: Retrospective case control study with 1:2 matching of cases (COVID-19+ patients) to controls (COVID-19- patients) based on age, gender, and race. Laboratory values assessed were serum D-dimer, fibrinogen, prothrombin time, international normalized ratio, and C-reactive protein. Demographic variables, comorbidities, and clinical variables including final disposition were also evaluated. P-values for categorical variables were calculated with the chi-square test or Fisher's exact test. P-values for continuous variables were compared with the use of a two-tailed unpaired t-test. RESULTS: The rate of extremity ultrasound exams positive for DVT were similar in patients with (14.7%) and without (19.3%) COVID-19 (P = .423). No significant difference was observed in laboratory values including the D-dimer level in COVID-19 patients without (mean 9523.9 ng/mL (range 339 to >60,000)) or with DVT (mean 13,663.7 ng/mL (range 1193->60,000)) (P = .475). No differences were found in demographic variabilities or co-morbidities among COVID-19 patients with and without extremity DVT. CONCLUSIONS: We found no statistically significant difference in rate of positive DVT studies between COVID-19+ and COVID-19- patients. D-dimer levels are elevated, in some cases markedly, in COVID-19 patients with and without DVTs and therefore these data do not support their use as a surrogate when assessing the need for ultrasound evaluation.

Clinical and laboratory characteristics of patients with novel coronavirus disease-2019 infection and deep venous thrombosis.

OBJECTIVE: Early reports suggest that patients with novel coronavirus disease-2019 (COVID-19) infection carry a significant risk of altered coagulation with an increased risk for venous thromboembolic events. This report investigates the relationship of significant COVID-19 infection and deep venous thrombosis (DVT) as reflected in the patient clinical and laboratory characteristics. METHODS: We reviewed the demographics, clinical presentation, laboratory and radiologic evaluations, results of venous duplex imaging and mortality of COVID-19-positive patients (18-89 years) admitted to the Indiana University Academic Health Center. Using oxygen saturation, radiologic findings, and need for advanced respiratory therapies, patients were classified into mild, moderate, or severe categories of COVID-19 infection. A descriptive analysis was performed using univariate and bivariate Fisher's exact and Wilcoxon rank-sum tests to examine the distribution of patient characteristics and compare the DVT outcomes. A multivariable logistic regression model was used to estimate the adjusted odds ratio of experiencing DVT and a receiver operating curve analysis to identify the optimal cutoff for d-dimer to predict DVT in this COVID-19 cohort. Time to the diagnosis of DVT from admission was analyzed using log-rank test and Kaplan-Meier plots. RESULTS: Our study included 71 unique COVID-19-positive patients (mean age, 61 years) categorized as having 3% mild, 14% moderate, and 83% severe infection and evaluated with 107 venous duplex studies. DVT was identified in 47.8% of patients (37% of examinations) at an average of 5.9 days after admission. Patients with DVT were predominantly male (67%; P = .032) with proximal venous involvement (29% upper and 39% in the lower extremities with 55% of the latter demonstrating bilateral involvement). Patients with DVT had a significantly higher mean d-dimer of 5447 ± 7032 ng/mL (P = .0101), and alkaline phosphatase of 110 IU/L (P = .0095) than those without DVT. On multivariable analysis, elevated d-dimer (P = .038) and alkaline phosphatase (P = .021) were associated with risk for DVT, whereas age, sex, elevated C-reactive protein, and ferritin levels were not. A receiver operating curve analysis suggests an optimal d-dimer value of 2450 ng/mL cutoff with 70% sensitivity, 59.5% specificity, and 61% positive predictive value, and 68.8% negative predictive value. CONCLUSIONS: This study suggests that males with severe COVID-19 infection requiring hospitalization are at highest risk for developing DVT. Elevated d-dimers and alkaline phosphatase along with our multivariable model can alert the clinician to the increased risk of DVT requiring early evaluation and aggressive treatment.

Five-Year Management of Vascular Injuries of the Extremities in the "Real-World" Setting in Northeastern Greece: The Role of Iatrogenic Traumas.

BACKGROUND: Vascular trauma comprises a diagnostic and surgical challenge. Aim of this study was to present the vascular traumas treated in our Tertiary Hospital during the last 5 years. METHODS: We retrospectively reviewed the surgical records of our vascular department and documented the site and type of vascular injuries of the extremities along with the concurrence of musculoskeletal injuries. The type and outcome of surgical interventions were also recorded. RESULTS: Fifty-eight cases of vascular trauma were recorded (39 in the upper and 19 in the lower extremities). Overall, iatrogenic traumas accounted for 41.3% of cases. The arterial injuries of the upper limb were blunt and penetrating in 27% and 67%, respectively. The most affected artery in the upper limb was the radial artery (37.8%), followed by the ulnar artery (27%) and the brachial artery (24.3%). Orthopedic injuries were recorded in 19% of patients. Management involved simple revascularization, bypass operations, patch arterioplasty and endovascular management in 48.7%, 33.3%, 5.1%, and 5.1%, respectively. The most affected site in the lower extremity was the common femoral artery (36.8%) followed by the popliteal artery (21%). Bone fractures were reported in 5 cases (26.3%). The surgical management involved bypass, simple revascularization, patch arterioplasty in 42.1%, 26.3%, and 21%, respectively. Endovascular management was performed in 10.5%. CONCLUSIONS: A considerable percentage of iatrogenic vascular injuries was recorded, affecting both the upper and lower limbs. Despite the trend toward centralization of vascular services, a basic service of vascular surgery should be available in most sites to ensure that patients with vascular injuries receive fast and appropriate care.

Acute limb ischemia among patients with COVID-19 infection.

OBJECTIVE/BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with thrombotic complications such as deep vein thrombosis or stroke. Recently, numerous cases of acute limb ischemia (ALI) have been reported although pooled data are lacking. METHODS: We systematically searched PubMed, Embase, Scopus, and the Cochrane Library for studies published online up to January 2021 that reported cases with SARS-CoV-2 infection and ALI. Eligible studies should have reported early outcomes including mortality. Primary endpoints included also pooled amputation, clinical improvement, and reoperation rates. RESULTS: In total, 34 studies (19 case reports and 15 case series/cohort studies) including a total of 540 patients (199 patients were eligible for analysis) were evaluated. All studies were published in 2020. Mean age of patients was 61.6 years (range, 39-84 years; data from 32 studies) and 78.4% of patients were of male gender (data from 32 studies). There was a low incidence of comorbidities: arterial hypertension, 49% (29 studies); diabetes mellitus, 29.6% (29 studies); dyslipidemia, 20.5% (27 studies); chronic obstructive pulmonary disease, 8.5% (26 studies); coronary disease, 8.3% (26 studies); and chronic renal disease, 7.6% (28 studies). Medical treatment was selected as first-line treatment for 41.8% of cases. Pooled mortality rate among 34 studies reached 31.4% (95% confidence interval [CI], 25.4%%-37.7%). Pooled amputation rate among 34 studies reached 23.2% (95% CI, 17.3%-29.7%). Pooled clinical improvement rate among 28 studies reached 66.6% (95% CI, 55.4%%-76.9%). Pooled reoperation rate among 29 studies reached 10.5% (95% CI, 5.7%%-16.7%). Medical treatment was associated with a higher death risk compared with any intervention (odds ratio, 4.04; 95% CI, 1.075-15.197; P = .045) although amputation risk was not different between the two strategies (odds ratio, 0.977; 95% CI, 0.070-13.600; P = .986) (data from 31 studies). CONCLUSIONS: SARS-CoV-2 infection is associated with a high risk for thrombotic complications, including ALI. COVID-associated ALI presents in patients with a low incidence of comorbidities, and it is associated with a high mortality and amputation risk. Conservative treatment seems to have a higher mortality risk compared with any intervention, although amputation risk is similar.

Review of COVID-19, part 2: Musculoskeletal and neuroimaging manifestations including vascular involvement of the aorta and extremities.

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world resulting in severe morbidity, mortality and economic hardship, altering the landscape of healthcare forever. Its devastating and most frequent thoracic and cardiac manifestations have been well reported since the start of the pandemic. Its extra-thoracic manifestations are myriad and understanding them is critical in diagnosis and disease management. The role of radiology is growing in the second wave and second year of the pandemic as the multiorgan manifestations of COVID-19 continue to unfold. Musculoskeletal, neurologic and vascular disease processes account for a significant number of COVID-19 complications and understanding their frequency, clinical sequelae and imaging manifestations is vital in guiding management and improving overall survival. The authors aim to provide a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19. In Part I, abdominal manifestations of COVID-19 in adults and multisystem inflammatory syndrome in children will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.

Novel fusion sarcomas including targetable NTRK and ALK.

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

Upper-Extremity Phlegmasia Cerulea Dolens With Compartment Syndrome in Coronavirus Disease 2019 Sepsis.

A 54-year-old woman with leukemia presented with coronavirus disease 2019 and a right upper-extremity indwelling peripherally inserted central catheter line for chemotherapy administration. On hospital admission day 9, she developed acute right upper-extremity edema and pain. Ultrasound demonstrated complete superficial and deep venous thrombosis up to the proximal subclavian vein. Her examination result was consistent with acute phlegmasia cerulea dolens and compartment syndrome, but respiratory instability prevented transfer and vascular surgery intervention. Instead, we performed bedside fasciotomies and administered therapeutic heparin, and the limb was salvaged. This case underscores the potential for successful limb salvage in patients with phlegmasia in the setting of coronavirus disease 2019 via compartment release and therapeutic anticoagulation.

Group A Streptococcus necrotising myositis of the limbs secondary to cavitating pneumonia.

Necrotising myositis is a rare complication of Group A Streptococcus infection requiring early and aggressive surgical management to prevent mortality. However, early diagnosis is difficult due to non-specific initial presentation and a low index of clinical suspicion given the paucity of cases. We highlight these challenges and present a case of a 22-year-old woman presenting with cough, fever and severe limb pain refractory to analgesia during the COVID-19 pandemic. We outline potential confounding factors that can delay intervention and offer diagnostic tools that can aid clinical diagnosis of necrotising myositis. In reporting this case, we hope to raise awareness among clinicians to avoid these pitfalls.

How Does SARS-CoV-2 Infection Affect Survival of Emergency Cardiovascular Patients? A Cohort Study From a German Insurance Claims Database.

OBJECTIVE: A previous study revealed a preliminary trend towards higher in hospital mortality in patients admitted as an emergency with acute stroke during the COVID-19 pandemic in Germany. The current study aimed to further examine the possible impact of a confirmed SARS-CoV-2 infection on in hospital mortality. METHODS: This was a retrospective analysis of health insurance claims data from the second largest insurance fund in Germany, BARMER. Patients hospitalised for ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction, acute limb ischaemia (ALI), aortic rupture, acute stroke, or transient ischaemic attack (TIA) between 1 January 2017, and 31 October 2020, were included. Admission rates per 10 000 insured and mortality were compared between March - June 2017 - 2019 (pre-COVID) and March - June 2020 (COVID). Mortality rates were determined by the occurrence of a confirmed SARS-CoV-2 infection. RESULTS: A total of 316 718 hospitalisations were included (48.7% female, mean 72.5 years), and 21 191 (6.7%, 95% CI 6.6% - 6.8%) deaths occurred. In hospital mortality increased during the COVID-19 pandemic when compared with the three previous years for patients with acute stroke from 8.3% (95% CI 8.0 - 8.5) to 9.6% (95% CI 9.1 - 10.2), while no statistically significant changes were observed for STEMI, NSTEMI, ALI, aortic rupture, and TIA. When comparing patients with confirmed SARS-CoV-2 infection (2.4%, 95% CI 2.3 - 2.5) vs. non-infected patients, a higher in hospital mortality was observed for acute stroke (12.4% vs. 9.0%), ALI (14.3% vs. 5.0%), and TIA (2.7% vs. 0.3%), while no statistically significant differences were observed for STEMI, NSTEMI, and aortic rupture. CONCLUSION: This retrospective analysis of claims data has provided hints of an association between the COVID-19 pandemic and increased in hospital mortality in patients with acute stroke. Furthermore, confirmed SARS-CoV-2 infection was associated with increased mortality in patients with stroke, TIA, and ALI. Future studies are urgently needed to better understand the underlying mechanism and relationship between the new coronavirus and acute stroke.

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study.

BACKGROUND: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. STUDY DESIGN: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. CONCLUSIONS: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

Severely injured patients do not disappear in a pandemic: Incidence and characteristics of severe injuries during COVID-19 lockdown in Finland.

Background and purpose - COVID-19 lockdowns have resulted in noteworthy changes in trauma admissions. We report and compare the incidence and characteristics of severe injuries (New Injury Severity Score [NISS] > 15) during the COVID-19 lockdown in Finland with earlier years.Methods - We retrospectively analyzed incidence rate, injury severity scores, injury patterns, and mechanisms of injury of all severely injured patients (NISS >15) in 4 Finnish hospitals (Tampere University Hospital, Kuopio University Hospital, Central Finland Hospital, Mikkeli Central Hospital) during the 11-week lockdown period (March 16-May 31, 2020) with comparison with a matching time period in earlier years (2016-2018). These 4 hospitals have a combined catchment area of 1,150,000 people or roughly one-fifth of the population of Finland.Results - The incidence rate of severe injuries during the lockdown period was 4.9/105 inhabitants (95% CI 3.7-6.4). The incidence rate of severe injuries during years 2016-2018 was 5.1/105 inhabitants (CI 3.9-6.5). We could not detect a significant incidence difference between the lockdown period and the 3 previous years (incidence rate difference -0.2 (CI -2.0 to 1.7). The proportion of traffic-related accidents was 55% during the lockdown period and 51% during previous years. There were no detectable differences in injury patterns. During the lockdown period, the mean age of patients was higher (53 years vs. 47 years, p = 0.03) and the rate of severely injured elderly patients (aged 70 or more) was higher (30% vs. 16%).Interpretation - Despite heavy social restrictions, the incidence of severe injuries during the lockdown period was similar to previous years. Notably, a decline in road use and traffic volumes did not reduce the number of severe traffic accidents. Although our data is compatible with a decrease of 2.0 to an increase of 1.7 severely injured patients per 105 inhabitants, we conclude that severely injured patients do not disappear even during pandemic and stabile hospital resources are needed to treat these patients.