Pre- and post-treatment in flexor tendon tenolysis: An observational study.

BACKGROUND: Glide deficit of the distal flexors' tendons following primary repair in zone 1-3 are very common. Adhesions of tendons have multi factorial origins and are closely related to the healing of the affected tissues. The surgical practice used to resolve these complications is tenolysis. PURPOSE: The purpose of this study was to identify and compare the Visual Analog Scale (VAS) relate to pain and Total Active Motion (TAM) of adult patients of both sexes undergoing tenolysis surgery. The results will then be compared to existing research to confirm their significance. STUDY DESIGN: Case-series. METHODS: Retrospective data for TAM and pain VAS were extracted from the medical records for 63 patients (73 fingers) who underwent flexor tenolysis between 2017 and 2019. Data were compared pre-operatively and 3 months after surgery. All patients underwent pre- and post-surgery therapy by hand therapists. RESULTS: The sample presented very encouraging improvements, except in the VAS and active range of motion (AROM) of thumb where some patients maintained the same assessment. The fingers reported statistically significant results, whereas the thumb group did not meet significant criteria. Overall, TAM improved from 134.6° to 196.7 and VAS decreased from 2.7 to 1.2. DISCUSSION: According to the results and the data change between pre- and post-treatment, the sample demonstrated improvements in all areas examined, reporting statistically significant results for the fingers with an improvement of TAM of 62.1° with a percentage value (%TAM) of 75.6%. CONCLUSIONS: A specific treatment for this type of surgery is required for the patients so they can return to their daily and working activities. This article can be used as a starting point for further studies.

Efficacy and safety of Dynavisc® gel in prevention of scar adhesions recurrence after flexor tendons tenolysis in zone 2. Multicenter retrospective cohort study.

AIM: Dynavisc® is a novel surgical product made of carboxymethylcellulose (CMC) and Polyethylene Oxide (PEO) designed to reduce post-surgical adhesions in tendons surgery. A multicenter retrospective cohort study was performed to investigate the clinical safety and efficacy of the Dynavisc® gel in reducing post-surgical adhesions after flexor tenolysis in zone 2. MATERIAL OF STUDY: Thirty-one patients suffering from stiff finger after flexor tendon repairs in zone 2 treated with standard release with (18 Dynavisc®-treated group) or without (13 controls) anti-adhesion gel application into the flexor tendon sheath and around the site of the tenolysis, were collected in five different hand surgery units. Safety profile and functional outcomes (based on TAM test and the The Quick-DASH questionnaire) were examined from patients' charts and analyzed. RESULTS: The application of Dynavisc® posed no safety concerns and it was not related to any additional complication. The Dynavisc®-treated group showed greater progressive improvement of TAM value in all visits with superior TAM value at T(90) and T(180) compared to the control group. DISCUSSION: Tendon adhesions are the main cause of flexor tendon surgery failure. Multiple strategies (i.e. robust tendon repair, early rehabilitation and lubricant or barrier agents) have been proposed to minimize their formation. Among different products described in the literature Dynavisc® showed a significant role in limiting adhesions formation in a recent experimental study. CONCLUSIONS: This clinical study confirm the safety of Dynavisc® gel application in hand surgery demonstrating its potential long-term benefits after flexor tendon tenolysis. KEY WORDS: Flexor Tendon Repair, Tendon Adhesions, Tenolysis.

Direct oral anticoagulant adsorption and laboratory detection of lupus anticoagulant.

Direct oral anticoagulants (DOACs) interfere with many coagulation assays, mostly in lupus anticoagulant (LA) detection, causing false positive and negative results. Despite guidelines recommendations, LA testing may be important during anticoagulation when the clinician has to decide whether to prolong or discontinue the drug. OBJECTIVES: In this study, the effect of activated charcoal (DOAC-Stop, DS) as a DOAC-adsorbent was investigated on samples from DOACs treated and untreated patients. BASIC METHODS: 165 plasma samples with a LA request were collected in three laboratories: 105 were from patients receiving DOACs and 60 were from nonanticoagulated patients with 30 LA negative and 30 LA positive. All coagulation screening assays and LA assays were evaluated before and after DS treatment. RESULTS: The adsorption technique reduced DOACs concentration below the Lower Limit of Quantification. For nonanticoagulated patients: no significant difference in ratio results of coagulation screening (prothrombin time, activated partial thromboplastin time and thrombin time) and LA tests were observed before and after addition of DS in LA positive and negative patients. Every LA was correctly classified. For anticoagulated patients: a statistically significant difference was found for coagulation screening assays and LA assays. Final LA conclusions changed after DS addition from positive to negative in 58.9% of patients (more frequently with Rivaroxaban) and from negative to positive in 8% of patients (more frequently with Apixaban). CONCLUSIONS: Our study suggests that DOAC-Stop can be used in daily laboratory practice to remove DOACs interference for a more accurate assessment of LA that is essential for diagnosis and management of APS patients.

Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants.

BACKGROUND: Postzygotic activating PIK3CA variants cause several phenotypes within the PIK3CA-related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007 PIK3CA-mutated patients, analysing our new data with previous literature to give a comprehensive picture. METHODS: We performed ultradeep targeted next-generation sequencing (NGS) on DNA from skin biopsy, buccal swab or blood using a panel including phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway genes and GNAQ, GNA11, RASA1 and TEK. Additionally, 914 patients previously reported were systematically reviewed. RESULTS: 93 of our 150 patients had PIK3CA pathogenetic variants. The merged PROS cohort showed that PIK3CA variants span thorough all gene domains, some were exclusively associated with specific PROS phenotypes: weakly activating variants were associated with central nervous system (CNS) involvement, and strongly activating variants with extra-CNS phenotypes. Among the 57 with a wild-type PIK3CA allele, 11 patients with overgrowth and vascular malformations overlapping PROS had variants in GNAQ, GNA11, RASA1 or TEK. CONCLUSION: We confirm that (1) molecular diagnostic yield increases when multiple tissues are tested and by enriching NGS panels with genes of overlapping 'vascular' phenotypes; (2) strongly activating PIK3CA variants are found in affected tissue, rarely in blood: conversely, weakly activating mutations more common in blood; (3) weakly activating variants correlate with CNS involvement, strong variants are more common in cases without; (4) patients with vascular malformations overlapping those of PROS can harbour variants in genes other than PIK3CA.

Hand and Upper Limb Malformations in Italy: A Multicentric Study.

Background: Although hand and upper limb malformations are quite frequent, up to now very few reports have been published on epidemiology. The aim of this study is to evaluate the number of infants who presented with hand and upper limb malformations from 2010 to 2015 in Italy. Methods: A retrospective analysis of a pediatric population presenting with hand and upper extremity malformations was carried out, gathering reports achieved from eight Italian Centers of pediatric hand surgery. Other factors such as gender, date and region of birth, family distribution of malformations and associated syndromes, were analysed. Results: Out of 3,100,421 live births, 765 children presented with hand and upper limb malformations. The incidence was 2,5/10,000 live births with a predominance of males and the right side. Radial polydactyly was the anomaly with the highest percentage, closely followed by simple syndactyly, simbrachidactyly and complex syndactyly. Less common conditions were the triphalangic thumb, thumb in palm, proximal radioulnar synostosis and Sprengel deformity. Inheritance of and familial predisposition to those malformations was recorded in 25 cases, while 84 children presented with syndromes related to hand anomalies. Conclusions: In conclusion the incidence of hand and upper extremity malformations in Italy is lower than that registered in other countries. The retrospective nature of the study combined with the fact that some defects frequently evade pediatric hand surgeon consultations are some possible limitations of the study. However, our data confirmed that, in spite of the decrease in the birth rate in Italy, the trend of congenital hand disorders maintained a stable trend. We aim to integrate this study with a prospective analysis and to involve the institutional health authorities in other countries so as to register the correct incidence of hand and upper extremity defects.

Heparin dosage, level, and resistance in SARS-CoV2 infected patients in intensive care unit.

INTRODUCTION: Patients with COVID-19 frequently exhibit a hypercoagulable state with high thrombotic risk, particularly those admitted to intensive care units (ICU). Thromboprophylaxis is mandatory in these patients; nevertheless, thrombosis still occurs in many cases. Thus, the problem of assessing an adequate level of anticoagulation in ICU patients becomes evident during the COVID-19 pandemic. The aim of this study was to evaluate the heparin resistance and the efficacy of heparin monitoring using an anti-Xa activity assay. METHODS: Thirty-seven heparin-treated patients admitted to ICU for SARS-CoV-2 pneumonia were retrospectively studied for antifactor Xa activity (anti-Xa), activated partial thromboplastin time (APTT), Antithrombin, Fibrinogen, D-Dimer, Factor VIII, von Willebrand Factor, and the total daily amount of heparin administered. The correlation between APTT and anti-Xa was evaluated for unfractionated heparins (UFH). The correlations between the daily dose of UFH or the dosage expressed as IU/kg b.w. for low molecular weight heparin (LMWH) and anti-Xa were also evaluated. RESULTS: Twenty-one patients received calcium heparin, 8 sodium heparin, and 8 LMWH. A moderate correlation was found between APTT and anti-Xa for UFH. APTT did not correlate with coagulation parameters. 62% of UFH and 75% of LMWH treated patients were under the therapeutic range. About 75% of patients could be considered resistant to heparin. CONCLUSIONS: SARS-COV2 pneumonia patients in ICU have frequently heparin resistance. Anti-Xa seems a more reliable method to monitor heparin treatment than APTT in acute patients, also because the assay is insensitive to the increased levels of fibrinogen, FVIII, and LAC that are common during the COVID-19 inflammatory state.

Iatrogenic anaemia and transfusion thresholds in ICU patients with COVID-19 disease at a tertiary care hospital.

BACKGROUND: Patients with severe COVID-19 disease frequently develop anaemia as the result of multiple mechanisms and often receive transfusions. The aims of this study were to assess the impact of repeated blood samplings on patients' anaemic state using standard-volume tubes, in comparison with the hypothetical use of low-volume tubes and to evaluate the transfusion policy adopted. STUDY DESIGN AND METHODS: Transfusion data of mechanically ventilated non-bleeding patients with COVID-19 disease hospitalized in ICU for a minimum of 20 days were recorded. The total volume of blood drawn for samplings with standard-volume tubes and the corresponding red blood cell mass (RBCM) removed during hospitalization for each patient were calculated and compared with the hypothetical use of low-volume tubes. RESULTS: Twenty-four patients fulfilled the inclusion criteria. Ten patients were anaemic at ICU admission (41.7 %). Overall, 6658 sampling tubes were employed, for a total of 16,786 mL of blood. The median RBCM subtracted by blood samplings per patient accounted for about one third of the total patients' RBCM decrease until discharge. The use of low-volume tubes would have led to a median saving of about one third of the drawn RBCM. Eleven patients were transfused (45.8 %) at a mean Hb value of 7.7 (± 0.5) g/dL. CONCLUSION: The amount of blood drawn for sampling has a significant role in the development of anaemia and the use of low-volume tubes could minimize the problem. Large high-powered studies are warranted to assess the more appropriate transfusion thresholds in non-bleeding critically ill patients with COVID-19 disease.

Inhibitory anti ADAMTS13 antibodies with a new rapid fully automated CLiA assay.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder characterized by severe ADAMTS13 deficiency. The acquired form is associated with autoantibodies directed against ADAMTS13. Both noninhibitory and inhibitory autoantibodies can be detected by ELISA assay, while only inhibitory autoantibodies are detected by Bethesda assay. Due to its short TAT and good performance, chemiluminescence (CliA) ADAMTS13 activity (HemosIL Acustar) has proven to be a good choice in the diagnosis of TTP in emergency settings. Aim of this study was to analyse the performance of the CliA ADAMTS13 activity assay in detecting inhibitory ADAMTS13 antibodies using the Bethesda assay. METHODS: A method comparison study was performed on 69 stored samples: 11 acute TTPs, 38 TTP follow-ups, 5 TTP relapses, 1 congenital TTP, 10 HUS, 4 suspected TTPs. We retrieved the results of tests previously run in ELISA for both activity and autoantibodies. At the same time, we reran new tests including ELISA and CliA activity, ELISA autoantibodies, and ELISA and CliA Bethesda assays on thawed frozen samples. RESULTS: Very good correlation was observed between ELISA and CliA activity assay results (r = 0.96) and between archived ELISA and CliA activity results (r = 0.93). Agreement between the anti-ADAMTS13 assays ranged from good (k = 0.63) to very good (k = 0.92). CONCLUSIONS: CliA and ELISA Bethesda assays showed very good agreement with samples run at the same time using ELISA ADAMTS13-autoantibody assay. Albeit more expensive, the CliA Bethesda assay identified inhibitory anti-ADAMTS13 within almost the same TAT as ELISA, but with better automation and limited operator involvement.

Efficacy of a strict surveillance policy towards inappropriateness of plasma transfusion.

BACKGROUND: Plasma transfusion is not without risks. Despite a limited spectrum of indications, plasma is frequently used as prophylaxis in non-bleeding patients, to correct altered coagulation tests. A high rate of inappropriate use of plasma transfusion is frequently reported, as well as underdosage. STUDY DESIGN AND METHODS: Since 2010 we started an education program that occurred in several phases to disseminate the knowledge of plasma transfusion guidelines. Since 2014 a 'zero tolerance' policy was applied: except for massive bleedings, plasma requests were prospectively evaluated, rejecting those without an appropriate indication. When indicated, at least 10 mL/Kg b.w.were issued. The previous five year period (2005-2009) served as control. RESULTS: The number of patients transfused/year decreased by 67.6% vs the control period (149 vs 460), and the liters of plasma issued/year decreased by 70.4% (233 vs 795). The deepest fall was observed in acute care wards (-70.8%). The mean volume transfused per episode raised from 731 mL ±â€¯70 to 879 mL ±â€¯154. The Prothrombin Time ratio at the moment of transfusion request increased from a mean of 1.35 (Interquartile range 1.20-2.64) in the control period to 1.62 (Interquartile range 1.43-1.98) in the last period (p < 0.001). CONCLUSION: With a proactive educational approach a remarkable reduction of plasma order and administration has been obtained, without any consequence on morbidity and mortality and with an estimated saving since 2014 of 750,000 €. A 'zero tolerance' policy can be effectively implemented only with a thorough workup with the local physicians, including repeated rounds of information and refreshing of the updated transfusion practice and knowledge of the established guidelines over the time.

Treatment and outcomes of arthrogryposis in the upper extremity.

Upper extremity involvement in patients with arthrogryposis multiplex congentia is quite frequent. Treatment initially consists of stretching and splinting as significant gains can be seen in the first years of life. The goal of any surgical procedure is to improve upper extremity function and performance of daily living activities, yet it is important to treat each patient individually and understand that areas do not always need to be addressed surgically. Despite overall lower functioning scores in this patient population, quality of life scores are comparable to the general aged adjusted population. This article will discuss the clinical presentation, treatment procedures and outcomes when addressing the upper extremities of patients presenting with arthrogryposis.

A collaborative study by the Working Group on Hemostasis and Thrombosis of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) on the interference of haemolysis on five routine blood coagulation tests by evaluation of 269 paired haemolysed/non-haemolysed samples.

INTRODUCTION: Haemolysis is the leading cause of sample rejection in laboratory haemostasis. Most studies focused on artificially haemolysed samples. The aim of this study was a prospective assessment of spontaneous haemolysis on haemostasis tests, by comparing results of haemolysed (H) versus new, non-haemolysed (NH) specimens, collected within 4hrs. As new coagulometers can identify interfering substances, visual assessment of haemolysis was also compared with instrumental haemolysis index and stratified in subclasses. MATERIALS AND METHODS: Two hundred and sixty nine paired samples were collected and analysed using ACL TOP750-CTS (Instrumentation Laboratory, Bedford, USA), for prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer (DD), fibrinogen (Fib) and antithrombin (AT). Bias between H and NH was calculated and compared with the respective critical difference (CD). RESULTS: Mean bias was - 0.1 s for PT (P = 0.057), - 1.1 s for aPTT (P < 0.001), 1025 ng/mL for DD (P < 0.001), - 0.04 g/L for Fib (P = 0.258) and 1.4% for AT (P = 0.013). Bias exceeding the CD varied according to the method, with larger differences for aPTT (36.1%) and DD (17.1%) and < 8% for PT, Fib and AT. No correlation emerged between free haemoglobin values and difference in haemostasis tests in H and NH samples for any tests. Moderate/severe haemolysis involved > 95% of samples. The agreement between visual assessment and instrumental evaluation of haemolysis was 0.62. CONCLUSION: Spurious haemolysis deeply influences aPTT and DD, and to a lesser extent AT and Fib. Prothrombin time seems only slightly influenced, suggesting that PT can be accepted also in haemolysed samples. Although a good inter-observer correlation of haemolysis evaluation was found, the instrumental assessment of haemolysis seems recommendable.

Treatment of the Upper Extremity Contracture/Deformities.

Patients with arthrogryposis multiplex congenita have a characteristic upper extremity resting posture consisting of internal rotation of the shoulders, elbow extension, flexed wrists, thumb-in palm deformities, and variable degrees of finger contractures. Treatment of these patients is aimed at improving independence and performance of activities of daily living. Although each area needs to be assessed independently for the most appropriate surgical procedure, often multiple areas can be addressed at the same operative setting. This limits the number of anesthetic exposures and cast immobilization time. The following is a synopsis of treatment strategies presented at the second international symposium on Arthrogryposis which took place in St Petersburg in September 2014.

Clinical usefulness of oral supplementation with alpha-lipoic Acid, curcumin phytosome, and B-group vitamins in patients with carpal tunnel syndrome undergoing surgical treatment.

We investigated the clinical usefulness of oral supplementation with a combination product containing alpha-lipoic acid, curcumin phytosome, and B-group vitamins in 180 patients with carpal tunnel syndrome (CTS), scheduled to undergo surgical decompression of the median nerve. Patients in Group A (n = 60) served as controls and did not receive any treatment either before or after surgery. Patients in Group B (n = 60) received oral supplementation twice a day for 3 months both before and after surgery (totaling 6 months of supplementation). Patients in Group C (n = 60) received oral supplementation twice a day for 3 months before surgery only. Patients in Group B showed significantly lower nocturnal symptoms scores compared with Group A subjects at both 40 days and 3 months after surgery (both P values <0.05). Moreover, patients in Group B had a significantly lower number of positive Phalen's tests at 3 months compared with the other study groups (P < 0.05). We conclude that oral supplementation with alpha-lipoic acid, curcumin phytosome, and B-group vitamins twice a day both before and after surgery is safe and effective in CTS patients scheduled to undergo surgical decompression of the median nerve.