Plasma exchange and intravenous immunoglobulin for the peri-operative management of type 2 heparin-induced thrombocytopaenia in a patient requiring urgent surgery for critical limb ischaemia.

We report the case of a 61-year-old female who developed heparin-induced thrombocytopaenia following treatment of a submassive pulmonary embolism, and who then required an above knee amputation for critical limb ischaemia. Heparin-induced thrombocytopaenia is a rare, immune-mediated complication associated with an in-hospital mortality rate of 10%. It is more common in surgical patients, with patients undergoing orthopaedic surgery more likely to develop it than patients undergoing cardiac surgery, but heparin-dependent immunoglobulin G antibodies are more likely to be formed in the latter. Peri-operative management remains a challenge. Ideally, it is preferable to wait for the platelet count to improve; but in certain cases, surgery cannot be delayed. Heparin-induced thrombocytopaenia is usually managed with direct thrombin inhibitors, such as argatroban and bivalirudin. Newer therapeutic modalities, such as plasmapheresis and intravenous immunoglobulin, as used in this case, can rapidly remove antibodies, but the certainty of evidence is low. Our case adds to the literature regarding the use of these modalities and highlights the multidisciplinary team approach required to manage such complex cases.

A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

OBJECTIVE: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. PATIENTS & METHODS: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. RESULTS: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. CONCLUSIONS: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults.

Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×10(9) (n=12), or 2×10(10) (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.

Test simultaneo de function ventricular y perfusion miocardica durante el ejercicio mediante un nuevo agente marcado con Tc99m / Simultaneous test of ventricular function and myocardial perfusion during exercise with a anew agent labelled with Tc99m

Utilizar un radiocompuesto con Tc99m para estudiar la perfusión miocárdica, permite determinar la función ventricular en la misma inyección, mediante la técnica de primer pasaje. Fueron estudiados 4 voluntarios normales, 14 pacientes con angina de esfuerzo y 2 portadores de miocardiopatía con coronarias normales. Todos fueron inyectados con 8-10mci de Tc99 carbometoxi-isopropil isonitrilo (CPI-Tc99m), o con 20mci de Tc99m-Nen-30, en el pico del ejercicio ergométrico y luego en reposo. Fue registrado el primer pasage del bolo radioactivo en imágenes de 30ms/frame. Se adquirieron luego a los 60 min las imágenes de perfusión correspondientes al esfuerzo, en las proyecriones anterior, OAI 45- y OAI 70-. Todos los pacietnes tenían realizado un estudio de perfusión de ejercicio con Talio 201 con similares niveles de esfuerzo. la fracción de eyección (FE) de ejercicio incrementó 69-76% en los normales; la perfusión miocárdica (PM) fue normal en todos ellos. En losportadores de miocardiopatía con coronarias normales, se observó disminución de la FE y la perfusión miocárdica con CPI-Tc99m. En los pacientes isquémicos la perfusión fue anormal en los 14 pacientes y la correlación con el Talio 201 fue excelente. Durante el ejercicio la FE incrementó en 4/14, disminuyó en 6/14 y permaneció sin cambios en 4/14. Estos resultados sugieren la posibilidad de utilizar el test simultáneo de perfusión y función ventricular con un solo ejercicio y radiocompuesto. La información de estos dos estudios mejoraría considerablemente la eficiencia del método, el cual podría convertirse en el test-radioisotópico estándar en el futuro

Inotropic contractile reserve: a useful predictor of increased 5 year survival and improved postoperative left ventricular function in patients with coronary artery disease and reduced ejection fraction.

The increase in left ventricular ejection fraction produced by postextrasystolic potentiation or epinephrine infusion has been used to demonstrate inotropic contractile reserve in patients with coronary artery disease and a depressed ejection fraction (less than 0.50). Prior studies have shown that a change in ejection fraction of 0.10 or more after postextrasystolic potentiation or epinephrine infusion is helpful in discriminating those patients with a better short-term (1 year) prognosis whether treated medically or surgically. This study related inotropic contractile reserve to 5 year prognosis in 54 patients receiving postextrasystolic potentiation or epinephrine infusion between 1971 and 1974. Current left ventricular function in surviving patients was assessed with radionuclide ventriculograms whenever possible. Five year survival was significantly better in patients with an initial change in ejection fraction greater than 0.10 in both the surgically treated group (16 of 20 versus 5 of 15, p less than 0.01) and the medically treated group (6 of 8 versus 1 of 11, p less than 0.01). Furthermore, among the surviving patients in the surgical group, current ejection fraction in the radionuclide ventriculogram was significantly greater in patients who demonstrated inotropic contractile reserve in their 1971 to 1974 contrast left ventriculogram. These findings support the concept that coronary revascularization enhances function of ischemic but viable myocardium.

Does phospholipase C stimulate thymide kinase activity of rat liver extracts prepared after partial hepatectomy.

Our purpose was to determine whether phospholipase C stimulated thymidine kinase activity of regenerating rat liver. We determined effects of phospholipase C upon TMP formation by rat liver extracts prepared at 0, 12, 24, 36 and 48 hr following partial hepatectomy. Data were obtained which supported these conclusions: (a) Commercial preparations of phospholipase C contained nucleoside phosphotransferase activity; (b) phospholipase C exerted no appreciable stimulatory influence upon thymidine kinase activity of regenerating rat liver; and (c), apparent stimulation of thymidine kinase was associated with linked activities of two enzymes, viz., liver extract-ATPase activity and nucleoside phosphotransferase activity.