The upper extremity regional anaesthesia trifecta: three upper extremity nerve blocks for awake upper-limb surgery in a patient with a history of contralateral pneumonectomy.

While regional anaesthesia plays a pivotal role in the perioperative management of patients undergoing upper extremity surgery, its utility can be limited by the risk of hemi-diaphragmatic paresis. Furthermore, each approach to blocking the brachial plexus has associated limitations that may result in incomplete upper extremity anaesthesia. We describe the combination of three upper extremity nerve blocks to achieve surgical anaesthesia of the whole arm for a patient who had previously undergone a contralateral pneumonectomy. On this occasion, she required upper arm lipectomy and arteriovenous fistula formation. Adequate blockade was achieved with no significant perioperative complications. This case demonstrates the potential of this approach for patients with respiratory compromise undergoing upper limb procedures.

Prognostic factors for surgical outcomes among patients with multilevel cervical spondylotic myelopathy.

OBJECTIVE: Many clinical and imaging characteristics can influence the prognosis of multilevel cervical spondylotic myelopathy (M-CSM). This study investigated the factors that influence surgical outcomes among patients with M-CSM. PATIENTS AND METHODS: This prospective study included 30 patients who underwent surgical treatment for M-CSM from June 2019 to June 2021. RESULTS: The average age was 62.29 years, and the average follow-up time was 13.13 months. Preoperative, postoperative, and follow-up Modified Japanese Orthopaedic Association (mJOA) scores were 10.17, 13.53, and 16.17, respectively. The average postoperative and follow-up recovery rates were 45.46% and 76.69%, respectively. Patients older than 60 years (p = 0.04), male patients (p = 0.023), and smokers (p = 0.027) had lower preoperative mJOA scores than other groups. Patients with symptoms duration longer than 6 months had lower recovery rates (p = 0.021) than those with shorter symptom duration. Patients with intramedullary hyperintensity in ≤ 2 vertebra (p = 0.041) or anterior surgery (p = 0.022) had better postoperative recovery rates than their counterparts. A shorter period of hyperintensity in the intramedullary region on sagittal T2-weighted magnetic resonance imaging (T2W MRI) was significantly associated with faster discharge (p = 0.044). Patients with type 3 (discrete focal) hyperintensity in the intramedullary region on axial T2W MRI had a 6.75-fold increase in experiencing less than 50% postoperative recovery compared with other groups (odds ratio: 6.75, 95% confidence interval: 2.73-16.67). CONCLUSIONS: Good prognostic factors for a shorter recovery included hyperintensity in the intramedullary region for ≤ 2 levels, shorter period of hyperintensity in the intramedullary region on sagittal T2W MRI, and an anterior surgical approach. A duration of symptoms longer than 6 months and discrete hyperintensity in the intramedullary region on axial T2W MRI were poor prognostic indicators associated with a longer recovery period.

Examining the link between thoracic rotation and scapular dyskinesis and shoulder pain amongst college swimmers.

OBJECTIVES: In National Collegiate Athletic Association Division I swimmers, we examined the differences in thoracic spine rotation in swimmers with and without scapular dyskinesis and the relationship between thoracic spine rotation and shoulder pain/dysfunction according to the Kerlan-Jobe Orthopaedic Clinic (KJOC) score. DESIGN: Cross-sectional. SETTING: Laboratory-based. PARTICIPANTS: 34 NCAA Division I swimmers (13 males, 21 females). MAIN OUTCOME MEASURES: Self-reported upper extremity function and pain assessed with the KJOC questionnaire, thoracic spine range of motion, presence of scapular dyskinesis. RESULTS: Dyskinesis was present in 15 of 34 (44%) subjects. Thoracic rotation averaged 136.7° and KJOC averaged 87.7 with no differences between swimmers with or without dyskinesis. We observed no correlation between KJOC-identified shoulder pain/dysfunction and thoracic rotation. CONCLUSIONS: In our cohort of NCAA Division 1 swimmers, no differences were found between swimmers with or without scapular dyskinesis and extent of thoracic rotation. We found no correlation between thoracic rotation and the amount of self-reported pain and dysfunction experienced in the upper extremity. The presence of scapular dyskinesis in nearly half of our subjects indicates that swimmers need to be assessed for this abnormality. If observed, rehabilitation should address the dyskinesis and improve thoracic rotation in an attempt to alleviate further upper extremity pain and dysfunction.

Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis.

BACKGROUND: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease. OBJECTIVE: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC). METHODS: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3. RESULTS: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm-2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells. CONCLUSIONS: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy.

Recent advances on lactose intolerance: Tolerance thresholds and currently available answers.

The genetically programmed reduction in lactase activity during adulthood affects 70% of the world adult population and can cause severe digestive disorders, which are the sign of lactose intolerance. Lactose intolerance symptoms vary depending on the residual lactase activity, the small bowel transit time, and especially the amount of ingested lactose. To formulate dairy products suitable for the vast majority of lactose intolerants, it is essential to define lactose intolerance threshold. A recent meta-analysis permitted to show that almost all lactose intolerants tolerate 12 g of lactose in one intake and approximately 18 g of lactose spread over the day. The prevalence and severity of lactose intolerance are probably overestimated by the general public. This misconception usually leads to an unnecessary reduction of dairy foodstuff consumption. Nevertheless, dairy products are essential for health mainly due to their calcium content and the positive influence of probiotic bacteria. The formulation of dairy products suitable for most intolerant and suspicious subjects seems necessary. The use of exogenous enzyme preparations, as well as the consumption of lactose-free products or products rich in probiotic bacteria are proposed as symptom-reducing strategies.

ZnO nanowires-C microfiber hybrid nanosensor for liquefied petroleum gas detection.

Zinc oxide nanowires are integrated onto carbon microfibers using a two-step approach which includes electrochemical deposition of zinc and its thermal oxidation. Such nano-on-micro hybrid architecture is then used as resistive gas sensor. Some properties like mechanical flexibility, low cost and large-area fabrication make this design appealing for different applications. The huge surface-to-volume ratio of such structure comes from being structured at both microscale and nanoscale (ZnO nanowires and C microfiber) and leads to a strong and rapid response/recovery times when it is used as a gas sensor. The fabrication process of the ZnO-microC device is very simple and doesn't involve any expensive lithographic step. The sensors show excellent liquefied petroleum gas sensing properties, with very fast response on gas exposure (about 3 s) and very good reversibility (less than 2%). In addition, the carbon microfiber substrate allows the use of the ZnO-microC sensor also in applications where flexibility is required (for example integrated in fabric).

Decrease in the plasma von Willebrand factor concentration following glucose ingestion: the role of insulin sensitivity.

Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age +/- SD, 40 +/- 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI(0,120)). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r =.43, P =.005). There were time effects for all variables of interest. While vWF antigen (P =.044), epinephrine (P =.003), and diastolic BP (P =.001) decreased after glucose challenge, norepinephrine (P =.009), systolic BP (P =.022), and heart rate (P <.001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r =.46, P =.004) and with screening systolic BP (r =.45, P =.004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI(0,120.) The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance.

Identification of anti-thrombin antibodies in the antiphospholipid syndrome that interfere with the inactivation of thrombin by antithrombin.

The combined presence of anti-phospholipid (PL) Ab, including lupus anticoagulants (LAC) and/or anticardiolipin Ab (aCL), and thrombosis is recognized as the antiphospholipid syndrome (APS). LAC are detected as an inhibitory effect on PL-restricted in vitro blood coagulation tests, and are comprised mainly of Ab against beta(2) glycoprotein I and prothrombin (PT). Recently, anti-PT Ab (aPT) were found to be associated with thrombosis by some investigators, although this is not confirmed by others. Considering that aPT are heterogeneous in patients and that PT is converted into thrombin, we hypothesize that certain aPT in patients may bind to thrombin, and that some of such anti-thrombin Ab may interfere with thrombin-antithrombin (AT) interaction and thus reduce the AT inactivation of thrombin. To test this hypothesis, we searched for anti-thrombin Ab in APS patients and then studied those found for their effects on the AT inactivation of thrombin. The results revealed that most, but not all, aPT-positive patient plasma samples contained anti-thrombin Ab. To study the functional significance of these Ab, we identified six patient-derived mAb that bound to both PT and thrombin. Of these mAb, three could reduce the AT inactivation of thrombin, whereas others had minimal effect. These findings indicate that some aPT in patients react with thrombin, and that some of such anti-thrombin Ab could inhibit feedback regulation of thrombin. Because the latter anti-thrombin Ab are likely to promote clotting, it will be important to develop specific assays for such Ab and study their roles in thrombosis in APS patients.

Severe alveolar proteinosis following chemotherapy for acute myeloid leukemia in a lung allograft recipient.

A 64-year-old man was diagnosed with acute myeloid leukemia (AML) 5 years following single lung transplantation performed for severe pulmonary hypertension from scleroderma. Chemotherapy for treatment of AML with fludarabine, cytosine arabinoside, G-CSF (FLAG) regimen was initiated. Despite intensive antibiotic treatment for a presumptive diagnosis of bacterial pneumonia, the patient developed acute respiratory failure and died before a complete cycle of chemotherapy could be administered. At autopsy, both native and allograft lungs showed widespread alveolar proteinosis that was determined as the main cause of acute respiratory failure. Alveolar proteinosis, a potentially treatable disease, should be considered in the radiologic differential diagnosis of diffuse lung disease in this clinical setting.

The hypercoagulable state in sleep apnea is related to comorbid hypertension.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with increased prevalence of atherosclerotic disease. A hypercoagulable state thought to underly atherosclerosis has been described in both OSA and systemic hypertension. We wondered about the respective contribution of apnea and hypertension to a hypercoagulable state. DESIGN: Eighty-seven subjects with symptoms suggestive of OSA, mean age 47 years (range 32-64 years), underwent polysomnography and blood pressure (BP) screening. OSA was diagnosed when respiratory disturbance index (RDI) > or = 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP (DBP) > 90 mmHg were classified as having hypertension. Three hypercoagulability markers were measured: thrombin/antithrombin III complex (TAT), fibrin D-dimer (DD), and von Willebrand factor antigen (vWF:ag). RESULTS: Analysis of variance and multiple linear regression were performed on the following four subject groups: (1) normotensive non-apneics (n = 19), (2) normotensive apneics (n = 38), (3) hypertensive non-apneics (n = 11), and (4) hypertensive apneics (n = 19). OSA (groups 2 and 4) had no significant main effect on hemostasis. Hypertensives (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range, 148/59-188 versus 77/53-108 pmol/l; P = 0.009) and of DD (376/265-721 versus 303/190-490 ng/ml; P = 0.040) than normotensives (groups 1 and 2). Across all subjects, SBP was the only significant predictor of TAT (P = 0.001) and of DD (P = 0.004), whereas DBP was the only significant predictor of vWF:ag (P = 0.029). These findings persisted even after controlling for gender, age, body mass index, RDI, mean SaO2, and hematocrit. CONCLUSION: Hypercoagulability in OSA is mediated by comorbid hypertension and might account for high cardiovascular morbidity in OSA in general.

Quantitative effects of nefiracetam on spatial learning of rats after cerebral embolism.

UNLABELLED: Recent studies have shown that nefiracetam ameliorates cognitive dysfunction because of ischemia when behavioral testing occurs during treatment. We sought to determine if there was a persistent effect after treatment, by testing spatial learning of embolized rats after nefiracetam therapy. METHODS: Male Sprague Dawley rats (250 to 300 g) were divided into 3 categories. The control group (n = 5) underwent no surgery or cerebral embolism. The vehicle group (n = 12) was anesthetized with halothane, underwent surgery, injected with intracarotid microspheres, and given orally 5 mL/kg of the vehicle (0.5% aqueous sodium carboxymethyl cellulose) for 21 days. The nefiracetam group (n = 12) was embolized and treated orally with 30 mg/kg nefiracetam (6 mg/mL in vehicle) for 21 days. Outcome was determined with visual spatial learning after the end of treatment. RESULTS: Embolization caused a significant impairment in visual spatial learning, which nefiracetam completely ameliorated (group main effect, F(2,444) = 6.4, P = .002). Mean latency to the escape was 35 +/- 6 seconds for the vehicle group versus 18 +/- 4 seconds for the nefiracetam group, after 4 days of testing. This effect persisted after a further interval of 10 days (retention test). A reversal test (to assess working memory for new information) yielded mean latencies of 26 +/- 6 seconds for the control group, 49 +/- 5 seconds for vehicle, and 25 +/- 4 seconds for nefiracetam (group main effect, F(2,109) = 8.0, P = .0005, Newman-Keuls, P < .05), showing that both the control and nefiracetam groups were different from the vehicle group. CONCLUSION: Nefiracetam therapy improves the learning behavior of embolized rats. The results are not caused by an activating effect of the drug because the animals are tested after the treatment period is over and because the beneficial effect is seen using the delayed retention test. Finally, working memory is markedly preserved by nefiracetam, an effect observed several weeks after treatment.

A novel clotting assay for quantitation of plasma prothrombin (factor II) using Echis multisquamatus venom.

Measuring plasma prothrombin activity seems useful for evaluating thrombotic risk and managing oral anticoagulant therapy as an adjunct to the international normalized ratio. Therefore, we designed a new plasma prothrombin assay based on the ability of Echis multisquamatus venom to activate prothrombin with only calcium as a cofactor. In this assay, 1 part of undiluted citrated plasma is added to 5 parts of a venom reagent and the clotting time is measured. The assay's advantages are that dilution of the test plasma is required only when prothrombin activity exceeds 100%, a single standard curve can be used over months for a given batch of stock reagent, and barium-adsorbed plasma is used for dilution of test plasma and construction of the standard curve, thus eliminating the need for prothrombin-deficient plasma. However, one should be aware of the following: (1) test samples must contain at least 200 mg/dL fibrinogen; and (2) when prothrombin concentrations were below 50%, the venom-based assay often gave values up to 10% higher than the thromboplastin-based assay. Values obtained in 262 plasma samples tested with the venom-based assay and with a thromboplastin-based prothrombin assay correlated well (r2 = 0.93).

An IgG antiprothrombin antibody enhances prothrombin binding to damaged endothelial cells and shortens plasma coagulation times.

OBJECTIVE: To test the hypothesis that some lupus anticoagulants are antiprothrombin antibodies, and that such antibodies enhance prothrombin binding to endothelial cells (EC) and thus promote clotting on the cell surface. METHODS: We generated a monoclonal antiprothrombin antibody (designated IS6) from a patient with primary antiphospholipid syndrome (APS). The antibody was analyzed for its binding properties, lupus anticoagulant activity, and pathophysiologic activity, using an EC-based plasma coagulation assay. RESULTS: IS6 is the first patient-derived monoclonal IgG antiprothrombin antibody. It bound to prothrombin with low affinity, reacted with 3 phospholipids (cardiolipin, phosphatidylethanolamine, and phosphatidylserine), and showed lupus anticoagulant activity. Moreover, IS6 enhanced the binding of prothrombin to damaged EC and shortened the EC-based plasma coagulation times. CONCLUSION: These findings suggest that IS6 may promote coagulation in areas of damaged EC in the host, and thus contribute to thrombosis in patients with APS.

Characterization of IgG monoclonal anti-cardiolipin/anti-beta2GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies.

Antiphospholipid antibodies (aPL), including antibodies detected in anti-cardiolipin (aCL) enzyme-linked immunosorbent assays and in lupus anticoagulant (LA) tests, are strongly associated with recurrent thrombosis and recurrent fetal loss, i.e. the antiphospholipid syndrome (APS). Although recent studies suggest that most APS-associated aCL are directed against the phospholipid (PL)-binding plasma protein beta2-glycoprotein 1 (beta2GP1), the precise nature of aCL binding specificities remains controversial. To address the issue of aCL specificity we generated five new monoclonal IgG aCL from two patients with APS. Characterization of these five aCL, as well as two previously published IgG aCL, revealed three patterns of reactivity: (1) four antibodies reacted strongly with human beta2GP1-cardiolipin (CL) complexes and weakly with human beta2GP1 alone; (2) two antibodies recognized bovine beta2GP1, but not human beta2GP1; (3) one antibody reacted with complexes of human beta2GP1 and CL, but not with human beta2GP1 alone. Only one monoclonal displayed weak LA activity. These patient-derived IgG monoclonal antibodies, and additional ones to be generated, may help define varying species of antibodies detected in aCL assays and identify the specific antibodies that may be pathogenic.

Hemostatic factors in rabbit limb lymph: relationship to mechanisms regulating extravascular coagulation.

Mechanisms regulating extravascular coagulation in interstitial fluids of peripheral tissues are poorly understood, since measurements of hemostatic factors in these fluids are unavailable. Because lymph from a body region reflects the composition of its interstitial fluid, we measured hemostatic factors in limb lymph of rabbits both as activity and as antigen. Mean lymph-to-plasma activity ratios were the following: fibrinogen, 0.28; prothrombin, 0.26; factor X, 0.27; factor VII, 0.17; and factors V and VIII, 0.08. All lymph fibrinogen was clottable; fibrin degradation products were absent. Lymph von Willebrand factor antigen was < 10% of plasma antigen and consisted primarily of lower molecular weight multimers. Mean lymph-to-plasma activity ratio for antithrombin was 0.38 and for tissue factor pathway inhibitor the ratio was 0.40. Low levels of antithrombin-factor Xa were measurable in lymph. The data are compatible with a basal factor VIIa-tissue factor-catalyzed extravascular activation of factor X that is prevented from progressing to generation of fibrin in limb interstitial fluid and lymph by low levels of factor VIII and factor V and by the inhibitory activity of antithrombin and tissue factor pathway inhibitor.

A Protac-based screening test for activated protein C-resistant factor Va and other defects of the protein C anticoagulant pathway.

We have standardized a simple screening test for abnormalities of the protein C anticoagulant system. The test is basically a modified prothrombin time in which one aliquot of a test plasma is incubated for 3 min at 37 degrees C with Protac and another is incubated with buffer. During the incubation the Protac activates both protein C and factor V. The plasmas are then clotted with thromboplastin plus Ca2+, and the clotting time difference reflects the ability of the activated protein C (APC) to inactivate factor Va. With the use of Thromboplastin C Plus as the activator, clotting time differences found in 31 normal subjects (10.4 +/- 3.5 s, mean +/- 2SD) were distinct from clotting time differences found in 57 of 58 subjects with established APC-resistant factor Va (3.6 +/- 3.0 s). In addition, the Protac-based test detected six of seven patients with isolated protein C deficiency and 20 of 28 patients with isolated protein S deficiency. Because of the reported high prevalence of heterozygous APC-resistant factor Va in Caucasian populations, it should be particularly useful in determining whether this genetic risk is present in individuals who have experienced or are at increased environmental risk of venous thrombosis.

Correction of excessive anticoagulation with low-dose oral vitamin K1.

BACKGROUND: Despite earlier acceptance of oral vitamin K1 (phytonadione) for the treatment of excessive anticoagulation, some recent guidelines do not recommend its use. OBJECTIVE: To reevaluate the efficacy of oral vitamin K1 in correcting excessive anticoagulation. DESIGN: Case series. SETTING: Anticoagulation clinics at two university medical centers. PATIENTS: 81 outpatients who had an international normalized ratio (INR) greater than 5.0 but did not have significant bleeding. INTERVENTIONS: Withholding 1 or 2 doses of warfarin, administering 2.5 mg of oral vitamin K1, measuring the INR after 24 to 48 hours, and adjusting the warfarin dose. MEASUREMENTS: INRs were obtained from a portable capillary fingerstick monitor or from an automated photooptical coagulometer. RESULTS: In 68 of 71 patients (96%), oral vitamin K1 lowered the INR from between 5.0 and 10.0 to less than 5.0 without inducing resistance to further anticoagulation. CONCLUSIONS: Withholding 1 or 2 doses of warfarin and administering 2.5 mg of oral vitamin K1 is a reliable, safe, and inexpensive way to rapidly correct excessive anticoagulation (INR > 5.0) in patients who do not have serious bleeding episodes and have an INR of less than 10.0.

Reliability of a modified tissue factor-dependent factor V assay for activated protein C resistant factor Va using a calcium-containing thromboplastin.

The original tissue factor-dependent factor V assay for activated protein C resistant factor Va (Blood 1995; 85: 1704-1711) has been modified to use a calcium containing thromboplastin and to express results as an observed to expected ratio (Obs/Exp.). The latter permits establishing a normal range independent of variations due to differences in reagents. Comparing Obs/Exp ratios with DNA analysis in 72 persons revealed that an Obs/Exp ratio of 0.6 distinguished without overlap normals from heterozygotes for FV R506Q. Three homozygotes had a ratio of < 0.1. Application of this Obs/Exp cut-off ratio of 0.6 to a total of 226 plasma samples tested to date discriminated without overlap between normals and heterozygotes. We conclude that this assay-readily adaptable to any dedicated coagulation laboratory and capable of yielding reliable results in all clinical circumstances in which testing is indicated-can distinguish between normals and heterozygotes for the FV R506Q mutation without the need for confirmatory DNA analysis.