Redox potential in human semen: Validation and qualification of the MiOXsys assay

Seminal oxidative stress (OS) is a major contributing factor to male infertility. Semen analysis cannot identify reactive oxygen species (ROS), which can be measured using a chemiluminescence assay. Measurement of redox potential provides a more comprehensive assessment of OS, although the test has yet to be fully validated. This study aimed to validate the MiOX^sys analyser for measuring static oxidation–reduction potential (sORP). Results demonstrated that duplicate measurements must be taken, sensors must be batch tested, and sockets should be regularly changed to avoid inconsistency in measurement. Measurement of sORP using MiOX^sys exhibited good reproducibility across different operators (p = 0.469), analysers (p = 0.963) and days (p = 0.942). It is not affected by mechanical agitation (p = 0.522) or snap freezing and thawing (p = 0.823). The stability of sORP over time requires further verification, particularly in samples with high initial sORP. Measurement is temperature sensitive between 2 and 37°C, significantly increasing with increasing temperature (p = 0.0004). MiOX^sys is a more stable assay for assessing OS than chemiluminescence methods and permits greater flexibility for sample handling. MiOX^sys could be implemented to complement semen analysis as part of routine diagnostic testing for male infertility and may be useful in identifying contributing factors to idiopathic infertility.     

Severity of Megakaryocyte-Driven Osteosclerosis in Mpig6b-Deficient Mice Is Sex-Linked

Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of myelofibrosis is linked to aberrant megakaryocyte development and function. Null and loss-of-function mutations in MPIG6B, which codes for the inhibitory heparan sulfate receptor G6b-B, result in severe macrothrombocytopenia, large megakaryocyte clusters, and focal primary myelofibrosis in mice and humans. We investigated the development of osteosclerosis in Mpig6b null (Mpig6b^−/−) mice. Although male and female Mpig6b^−/− mice presented with elevated bone marrow megakaryocyte number and macrothrombocytopenia, female Mpig6b^−/− mice developed progressive splenomegaly starting at 8 weeks of age. Micro–computed tomography (μCT) of femurs showed that female Mpig6b^−/− mice had increased cortical thickness and reduced bone marrow area starting at 8 weeks of age and developed occlusion of the medullary cavity by trabeculae by 16 weeks of age. In contrast, male Mpig6b^−/− mice developed only a small number of trabeculae in the medullary cavity at the proximal diaphysis and demonstrated a temporary decrease in bone volume fraction and trabecular thickness at 16 weeks. Ovariectomy of 10-week-old female Mpig6b^−/− mice prevented the development of medullary cavity osteosclerosis, whereas orchiectomy of male Mpig6b^−/− mice did not exacerbate their disease. Importantly, ovariectomized female Mpig6b^−/− mice also demonstrated improvement in spleen weight compared to sham-operated Mpig6b^−/− mice, establishing estrogen as a contributing factor to the severity of the megakaryocyte-driven osteosclerosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

A simple scoring system to estimate perioperative mortality following liver resection for primary liver malignancy—the Hepatectomy Risk Score (HeRS)

BackgroundSelection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections.MethodsThe 2005–2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7–10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1–4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values.ResultsA total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16–8.99), P=0.025; HeRS =3: OR =6.54 (2.39–17.90), P<0.001; HeRS =4: OR =13.69 (4.90–38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model.ConclusionsThe HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.     

Results of combined therapy of irradiation and intra-arterial one-shot injection of cisplatin for head and neck cancers

Thirty-six previously untreated cases of head and neck cancer were given a combined therapy of irradiation and intra-arterial, one-shot injection of Cisplatin. As a result, the primary lesions in 35 cases were seen to achieve a 66% complete remission (CR) and a 100% overall response (OR). The lymph metastases in twenty-one cases with positive node achieved a 62% CR and a 100% OR. Good, local control of supraglottic and hypopharyngeal cancers were found to be an advantageous factor considered from the standpoint of the "quality of life". The cumulative survival rate, using Kaplan-Meier's method, was 82% for the first year, and 62% for the second year. No severe side effects were observed.     

Quantitative description of the far-lateral transcondylar transtubercular approach to the foramen magnum and clivus

OBJECT: The purpose of this study was to evaluate the far-lateral transcondylar transtubercular approach (complete FLA) based on quantitative measurements of the exposure of the foramen magnum and petroclival area obtained after each successive step of this approach. METHODS: The complete FLA was reproduced in eight specially prepared cadaveric heads (a total of 15 sides). The approach was divided into six steps: 1) C-1 hemilaminectomy and suboccipital craniectomy with unroofing of the sigmoid sinus (basic FLA); 2) partial resection of the occipital condyle (up to the hypoglossal canal); 3) removal of the jugular tuberculum; 4) mastoidectomy (limited to the labyrinth and the fallopian canal) and retraction of the sigmoid sinus; 5) resection of the lateral mass of C-1 with mobilization of the vertebral artery; and 6) resection of the remaining portion of the occipital condyle. After each successive step, a standard set of measurements was obtained using a frameless stereotactic device. The measurements were used to estimate two parameters: the size of the exposed petroclival area and the size of a spatial cone directed toward the anterior rim of the foramen magnum, which depicts the amount of surgical freedom available for manipulation of instruments. The initial basic FLA provided exposure of only 21 +/- 6% of the petroclival area that was exposed with the full, six-step maximally aggressive (complete) FLA. Likewise, only 18 +/- 9% of the final surgical freedom was obtained after the basic FLA was performed. Each subsequent step of the approach increased both petroclival exposure and surgical freedom. The most dramatic increase in petroclival exposure was noted after removal of the jugular tuberculum (71 +/- 12% of final exposure), whereas the least improvement in exposure occurred after the final step, which consisted of total condyle resection. CONCLUSIONS: The complete FLA provides wide and sufficient exposure of the foramen magnum and lower to middle clivus. The complete FLA consists of several steps, each of which contributes to increasing petroclival exposure and surgical freedom. However, the FLA may be limited to the less aggressive steps, while still achieving significant exposure and surgical freedom. The choice of complete or basic FLA thus depends on the underlying pathological condition and the degree of exposure required for effective surgical treatment.