A 30-Year-Old Man with an Unusually Large Untreated Plantar Fibrolipoma That Disrupted Ambulation and Required Operative Excision.

A 30-year-old man working as a waiter presented with a progressively enlarging and symptomatic soft-tissue mass on the plantar medial aspect of his left foot. The mass was painful and disrupting ambulation, despite footwear modifications. He ultimately underwent excision of what was a determined to be a fibrolipoma, returning to his regular shoes and all activities. Plantar neoplasms, even when benign, can grow to sizes that can result in significant disability. If left untreated, particularly in individuals engaged in occupations requiring frequent standing or walking, excision of the mass will often require a more aggressive operative approach.

Angioleiomyoma (Vascular Leiomyoma) Presenting as a Pseudoaneurysm of the Tibialis Posterior Artery.

Reported here is the case of a 55-year-old woman presenting to a podiatry clinic with a chief complaint of left heel and ankle pain, who ultimately underwent operative excision of an angioleiomyoma adjacent to the tibialis posterior artery at the level of the medial malleolus. Accompanying this case are images from three modalities through which the defining characteristics of an angioleiomyoma can be appreciated. This case advocates for the inclusion of angioleiomyoma in the preoperative differential diagnosis of a mass presenting as a pseudoaneurysm in the lower extremity, particularly among women in the fourth to sixth decades of life.

Foot Pain in Relation to Ipsilateral and Contralateral Lower-Extremity Pain in a Population-Based Study.

BACKGROUND: Clinical observations note that foot pain can be linked to contralateral pain at the knee or hip, yet we are unaware of any community-based studies that have investigated the sidedness of pain. Because clinic-based patient samples are often different from the general population, the purpose of this study was to determine whether knee or hip pain is more prevalent with contralateral foot pain than with ipsilateral foot pain in a population-based cohort. METHODS: Framingham Foot Study participants (2002-2008) with information on foot, knee, and hip pain were included in this cross-sectional analysis. Foot pain was queried as pain, aching, or stiffness on most days. Using a manikin diagram, participants indicated whether they had experienced pain, aching, or stiffness at the hip or knee and specified the side of any reported pain. Sex-specific multinomial logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals for the association of foot pain with knee and hip pain, adjusting for age and body mass index. RESULTS: In the 2,181 participants, the mean ± SD age was 64 ± 9 years; 56% were women, and the mean body mass index was 28.6. For men and women, bilateral foot pain was associated with increased odds of knee pain on any side (ORs = 2-3; P < .02). Men with foot pain were more likely to have ipsilateral hip pain (ORs = 2-4; P<.03), whereas women with bilateral foot pain were more likely to have hip pain on any side (OR = 2-3; P < .02). CONCLUSIONS: Bilateral foot pain was associated with increased odds of knee and hip pain in men and women. For ipsilateral foot and hip pain, men had a stronger effect compared with women.

Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry.

The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Adverse events in apheresis: An update of the WAA registry data.

Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

Ankle Impingement Caused by an Intra-articular Plica: A Report of 2 Cases.

UNLABELLED: Entrapment of soft tissues in the anterolateral gutter of the ankle can cause impingement. When symptomatic, patients complain of chronic ankle pain exacerbated with dorsiflexion. Symptoms of instability and a history of recurring ankle sprains are common findings. Plain radiographs and magnetic resonance imaging may assist clinicians in identifying associated pathology. We present 2 cases of ankle impingement occurring in the setting of equivocal examination and imaging findings. In both cases, arthroscopy revealed a likely congenital, intra-articular plica. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case Study.

Ultrasound diagnosis and evaluation of plantar heel pain.

BACKGROUND: One of the most common causes of heel pain is plantar fasciitis; however, there are other pathologic disorders that can mimic the symptoms and clinical presentation of this disorder. The purpose of this study was to retrospectively review the prevalence of various pathologic disorders on ultrasound in patients with proximal plantar heel pain. METHODS: The medical records and diagnostic ultrasound reports of patients presenting with plantar heel pain between March 1, 2006, and March 31, 2007, were reviewed retrospectively, and the prevalence of various etiologies was collected. The inclusion criteria were based on their clinical presentation of plantar fasciitis or previous diagnosis of plantar fasciitis from an unknown source. Ultrasound evaluation was then performed to confirm the clinical diagnosis. RESULTS: We examined 175 feet of 143 patients (62 males and 81 females; age range, 16-79 years). Plantar fibromas were present in 90 feet (51%). Plantar fasciitis was diagnosed in 128 feet (73%). Coexistent plantar fibroma and plantar fascial thickening was found in 63 feet (36%). Of the 47 feet that were negative for plantar fasciitis on ultrasound, 27 (57%) revealed the presence of plantar fibroma. CONCLUSIONS: Diagnostic ultrasound can effectively and safely identify the prevalence of various etiologies of heel pain. The high prevalence of plantar fibromas and plantar fascial tears cannot be determined by clinical examination alone, and, therefore, ultrasound evaluation should be performed for confirmation of diagnosis.

Serological and molecular evidence of a plausible transmission of hepatitis E virus through pooled plasma.

BACKGROUND AND OBJECTIVES: Recently, hepatitis E virus has been recognized as a new transfusion-associated risk; however, its efficiency of transmission through blood products requires further investigation. Asymptomatic viremia of short duration has been observed in blood donors from several European countries to the rate of <1:10,000 and HEV transmission in recipients of blood products has been documented in Japan and Europe. Although HEV RNA was detected in large plasma fractionation pools used for manufacturing of plasma derived products, HEV transmission has not been demonstrated so far. In this study, we investigated the possibility of HEV transmission in patients with thrombotic thrombocytopenic purpura whose treatment included up to 40 l of plasma exchange. MATERIALS AND METHODS: Thirty-six TTP patients received either solvent-detergent-treated plasma prepared by pooling of 2500 single-donor or cryosupernatant plasma. Three samples were collected from TTP patients at time 0, 1 and 6 months post-treatment and tested for anti-HEV antibodies. Patients with HEV seroconversion were also tested for viremia by PCR. RESULTS: Two of seventeen TTP patients treated with SDP showed serological evidence of HEV infection. The 1-month samples from these patients were also positive for HEV RNA. A distinct rise of anti-HEV IgG level was detected in two other TTP patients with weak pre-existing immunity to HEV; this observation is indicative of a possible immune response boost due to a breakthrough infection. CONCLUSION: This work provides, for the first time, indirect evidence of HEV transmission by pooled plasma and warrants further studies.

ADAMTS-13 may not predict disease or outcome in patients with Thrombotic Thrombocytopenic Purpura.

BACKGROUND: The pathophysiology of Thrombotic Thrombocytopenia Purpura (TTP) has been questioned since described in 1924. In 1998, Tsai [1] and Furlan [2] demonstrated a relationship of low levels of ADAMTS-13 with an IgG inhibitor in acquired idiopathic TTP. This study reports on a series of TTP patients treated with solvent/detergent plasma (SDP) or cryosupernatant plasma (CSP) and focuses on the correlation of their presentation, clinical response and outcome with the levels of ADAMTS-13, the inhibitor and VWF multimers. METHODS: Plasma exchange was carried out in patients with the clinical diagnosis of acquired idiopathic TTP. ADAMTS-13 enzyme activity and inhibitor levels, VWF multimers and platelet count were analyzed in correlation with patient outcome. This RCT was intended to compare outcome in 280 patients treated either with cryosupernatant or solvent-detergent heated plasmas. The primary end point was survival at six months. RESULTS: Data on 61 TTP patients were obtained from 16 centres across Canada. The study was then closed prematurely due to removal of one of the interventional products from the market. ADAMTS-13 enzyme activity and inhibitor levels varied considerably among study participants. At baseline, only 12/49 (24.5%) had ≤10% enzyme activity and 20/49 (41%) had levels ≥80%; whereas 16/49 had ≥80% inhibitors; 19/49 had ≤10% inhibitors 18/49 (37%) had no inhibitors. No unusually large VWF multimers were identified in any of the patients at presentation. The 6-month, all-cause mortality rates for patients randomized to receive CSP vs. SDP were 3/34 (9%; 95% CI: 3%, 23%) and 1/27 (4%; 95% CI: 1%, 18%), respectively, with a difference of 5% (95% CI: -11%, 20%). CONCLUSION: Although this study was underpowered to compare solvent/detergent vs. cryosupernatant plasma, our data suggest that ADAMTS-13 activity and inhibitor level at baseline cannot differentiate TTP response to plasma exchange therapy.

The occurrence of ipsilateral or contralateral foot disorders and hand dominance: the Framingham foot study.

BACKGROUND: To our knowledge, hand dominance and side of foot disorders has not been described in the literature. We sought to evaluate whether hand dominance was associated with ipsilateral foot disorders in community-dwelling older men and women. METHODS: Data were from the Framingham Foot Study (N = 2,089, examined 2002-2008). Hand preference for writing was used to classify hand dominance. Foot disorders and side of disorders were based on validated foot examination findings. Generalized linear models with generalized estimating equations were used to estimate odds ratios and 95% confidence intervals, accounting for intraperson variability. RESULTS: Left-handed people were less likely to have foot pain or any foot disorders ipsilateral but were more likely to have hallux valgus ipsilateral to the left hand. Among right-handed people, the following statistically significant increased odds of having an ipsilateral versus contralateral foot disorder were seen: 30% for Morton's neuroma, 18% for hammer toes, 21% for lesser toe deformity, and a twofold increased odds of any foot disorder; there was a 17% decreased odds for Tailor's bunion and an 11% decreased odds for pes cavus. CONCLUSIONS: For the 2,089 study participants, certain forefoot disorders were shown to be ipsilateral and others were contralateral to the dominant hand. Future studies should examine whether the same biological mechanism that explains ipsilateral hand and foot preference may explain ipsilateral hand dominance and forefoot disorders.

Thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). There are many secondary causes of TMA, many of them could mimic TTP or HUS. This article presents a short overview on TMA. In conclusion TMA is the result of various etiology reasons and pathologic reactions with various clinical entities. It is important to focus on a thorough history including family history when deciding on a diagnosis. Analysis of ADAMTS 13 and ADAMTS 13-antibodies may help to decide continued therapy.

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.

UNLABELLED: Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. MATERIALS AND METHODS: Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. RESULTS: The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034). CONCLUSIONS: Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels.

A comparison of methods of pathogen inactivation of FFP.

INTRODUCTION: Current methods for pathogen inactivation of plasma involve four major processes using solvent-detergent (SD), methylene blue (MB), amotosalen and riboflavin as additives. Three of these methods involve the use of visible or ultraviolet light. METHODS: A comparison of the four methods was made using publications in Medline, Pubmed, Embase and Biosis to obtain data on the logistics of use, the quality of the plasma proteins and the effectiveness of pathogen inactivation. RESULTS: Three of the methods, MB, amotosalen and riboflavin, are designed for use in a blood bank; the SD method is generally applied at a centralized manufacturing centre and involves large plasma pools. All methods result in a reduction in protein values with the per cent retention of FVIII activity in the range of 67-78% and fibrinogen of 65-84%. Protein S and alpha(2)-antiplasmin are lower following solvent-detergent treatment. Alterations in fibrinogen structure have been reported with methylene blue. DISCUSSION: Three of the methods are designed for small volume use in a blood bank. All four methods have some effect on the coagulant proteins; however, the final concentrations are within regulated limits. While there is variability in the effectiveness against pathogens, direct comparison is difficult because of the methodologies used. Nonetheless, all are effective in inactivating HIV and other lipid-enveloped pathogens. Clinical studies on the effectiveness of these products are surprisingly sparse, and no randomized clinical trials have yet been performed with amotosalen or riboflavin plasmas.

Analysis of the products of cryoprecipitation: RiCoF is deficient in cryosupernatant plasma.

INTRODUCTION: Cryoprecipitate and its byproduct, cryosupernatant plasma (CSP) have been used to treat specific medical diseases such as hemophilia, von Willebrand disease and thrombotic thrombocytopenia purpura. Cryoprecipitate is also widely used to prepare fibrin glue. In many instances, it is given to augment fresh frozen plasma when patients are bleeding. However, the full range of constituents of cryoprecipitate and CSP are not widely appreciated. METHODS: To determine the concentration of the various constituents in plasma and its frozen fractions, we measured levels of Factor VIII, von Willebrand factor antigen, fibrinogen, Factor V, ATIII, functional and antigenic proteins C and S, plasminogen, Total protein, fibronectin, Factor XIII, RiCoF and von Willebrand factor multimers in the starting plasma, the cryoprecipitate and the CSP produced from the plasma in each of the blood groups. RESULTS: While only 4% of the plasma proteins cryoprecipitate, there is considerable enrichment of Factor VIII, von Willebrand factor and RiCoF. However, cryoprecipitate contains only 27% of the plasma fibrinogen and has low levels of Factor V, protein S, protein C, ATIII and plasminogen. Factor VIII and von Willebrand factor are much reduced in the cryosupernatant plasma (0.20 U/ml and 0.16 U/ml) and there is virtually no ristocetin cofactor activity. This is consistent with the absence of the higher molecular weight multimers of VWF found in CSP. The ADAMTS-13 levels are the same as in plasma. All levels vary between blood groups. CONCLUSIONS: While cryoprecipitate is relatively enriched in certain factors, the process does not result in concentration of other coagulation factors so cryoprecipitate cannot be used for the replacement of protein C, protein S or Factor V. SCP is deficient in RiCoF.

Characterization of plasma protein activity in riboflavin and UV light-treated fresh frozen plasma during 2 years of storage at -30 degrees C.

BACKGROUND: The Mirasol Pathogen Reduction Technology System (PRT) for Plasma (CaridianBCT) is based on a riboflavin and UV light treatment process resulting in pathogen inactivation due to irreversible, photochemically induced damage of nucleic acids. This study evaluated the in vitro protein quality of plasma products treated with riboflavin and UV light following treatment and subsequent storage for up to 104 weeks at -30 degrees C. MATERIALS AND METHODS: Apheresis and whole blood-derived plasma products were combined with riboflavin solution and exposed to ultraviolet light. Treated plasma was then flash frozen, within 8 h of collection, stored at -30 degrees C for up to 104 weeks and analysed at different stages of storage using standard coagulation assays. Results were compared with paired, untreated units stored for the same intervals. RESULTS: The average percent protein retention for all time-points in PRT-treated plasma samples after 36, 69, 87 and 104 weeks of storage at -30 degrees C in comparison with controls held under similar conditions were: Total Protein, 101%, Factor VIII, 79%, Fibrinogen, 78%, Factor II, 87%, Factor XII, 86%, Factor X, 84% and Factor IX, 81%. Anticoagulant and inhibitor proteins showed between 90% and 100% retention after 1 year (52 weeks) and 69 weeks of storage. No clinically relevant complement activation was observed in treated and stored samples. CONCLUSION: Riboflavin and UV light-treated plasma demonstrates reductions in several plasma coagulation factors following treatment. This reduction in activity levels is noted immediately after treatment and remains relatively constant during 2 years of storage at -30 degrees C.

Histopathology of fatal respiratory distress caused by Plasmodium vivax malaria.

An otherwise healthy 20-year-old woman in Goa, India, received antibiotics after a diagnosis of upper respiratory tract infection. One week later, vivax malaria was diagnosed at a health center, but the patient developed respiratory distress and lost consciousness. She arrived at emergency department in shock, breathless, and comatose. She died within minutes. Two independent laboratories later confirmed Plasmodium vivax by microscopy (140,000/microL) and by nested and real-time polymerase chain reaction methods. Post-mortem examination showed congestion of alveolar capillaries by heavy monocytic infiltrates, along with diffuse damage to alveolar membranes consistent with acute respiratory distress syndrome. Parasites seen in lung tissue were roughly proportionate to both peripheral hyperparasitemia and those seen in other organs without lesions. In this patient, vivax malaria caused a rapidly fatal respiratory distress.