Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status.

BACKGROUND & AIMS: Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We summarize the efficacy and safety data of tofacitinib 5 or 10 mg twice daily in the UC clinical program, stratified by prior tumor necrosis factor inhibitor (TNFi) failure status. METHODS: Efficacy was assessed in the pooled phase 3 OCTAVE Induction 1 and 2 studies (N = 1139), the phase 3 OCTAVE Sustain maintenance study (N = 593), and the dose-escalation subpopulation of the open-label, long-term extension OCTAVE Open study (N = 59). Safety was assessed in OCTAVE Sustain, the dose-escalation subpopulation, and the Overall Cohort, which included patients from OCTAVE Induction 1 and 2, OCTAVE Sustain, and OCTAVE Open (N = 1124; no prior TNFi failure N = 541; prior TNFi failure N = 583; phase 2 data were excluded when stratified by prior TNFi failure status). The dose-escalation subpopulation received tofacitinib 10 mg twice daily in OCTAVE Induction 1 and 2, tofacitinib 5 mg twice daily in OCTAVE Sustain, and tofacitinib 10 mg twice daily in OCTAVE Open. RESULTS: Tofacitinib had greater efficacy than placebo, regardless of prior TNFi failure status. In OCTAVE Sustain and the Overall Cohort, herpes zoster [HZ] (nonserious and serious) rates were numerically higher in tofacitinib-treated patients with vs without prior TNFi failure. Dose escalation to tofacitinib 10 mg twice daily generally recaptured clinical response for most patients. HZ (nonserious and serious) rates were numerically higher in the dose-escalation subpopulation vs the Overall Cohort. CONCLUSIONS: Tofacitinib was efficacious in patients with UC regardless of prior TNFi failure status. HZ (nonserious and serious) rates were numerically higher in patients who had previously failed TNFi. ClinicalTrials.gov: A3921063 (NCT00787202); OCTAVE Induction 1 (NCT01465763); OCTAVE Induction 2 (NCT01458951); OCTAVE Sustain (NCT01458574); and OCTAVE Open (NCT01470612).

Transsternal repair of Morgagni hernia in a patient with coexistent ventricular septal defect and Down syndrome.

BACKGROUND: Morgagni hernia is a rare diaphragmatic hernia occurring secondary to potential anterior medial defects in the diaphragm. The association of the defect with congenital cardiac pathologies and Down syndrome has already been reported. The defect is repaired usually by transabdominal or transthoracic approaches. Transsternal repair of the hernia is preferred in patients undergoing concomitant open heart surgery. CASE: An eight-month old child with Down syndrome and congenital hypothyroidism underwent concomitant repair of Morgagni hernia and closure of his ventricular septal defect under cardiopulmonary bypass. The hernia was repaired by the sternotomy approach, without opening the hernia content, before the correction of the cardiac pathology. COMMENT: As Morgagni hernia can accompany some congenital cardiac anomalies, cardiac surgeons should be familiar with the transsternal approach to the defect which is as effective as other surgical approaches.

Sialic acid is an indicator of inflammation due to cardiopulmonary bypass but not myocardial damage.

BACKGROUND: The aim of the present study was to investigate whether serum sialic acid is associated with the inflammatory response of cardiopulmonary bypass (CPB) or not, since cardiopulmonary bypass is known to produce a systemic inflammatory syndrome. METHODS: In 20 patients in whom elective coronary bypass grafting was done, arterial and coronary sinus blood sampling was done simultaneously. The timing of samplings was 8-10 min after the institution of CPB, just before the application of aortic clamping (T1) and 2 min after cross clamp removal (T2), when there was coronary circulation, but no myocardial activation. RESULTS: Sialic acid, CK-MB, lactate levels were significantly higher at T2 than those at T1 for both arterial and coronary sinus samples. Increase at T2 time point for SA, CK-MB and lactic acid at coronary sinus were closely correlated with the systemic increase of these substances also. Actually, increase of systemic and coronary sinus CK-MB levels was also correlated with the duration of aortic cross-clamping and cardiopulmonary bypass. Probably due to consumption, a negative correlation with the decrease of fibrinogen at coronary sinus was found with the duration of aortic cross-clamping. CONCLUSIONS: Our study showed a strong and consistent association between serum SA concentration and the inflammatory process. There are previous reports that show sialic acid levels associated with ischemic insult to myocardium. We are able to show that serum TSA correlates well with some of the acute phase proteins but this was not true with ischemic markers after cardioplegic arrest.

Bilateral chylothorax caused by pleuropulmonary lymphangiomyomatosis: a challenging problem in thoracic surgery.

Massive left-sided pleural effusion in a 35-year-old man was initially diagnosed as idiopathic spontaneous chylothorax and treated with serial thoracenteses and left thoracotomy. Six weeks later, a right thoracotomy was performed for contralateral chylothorax, and histologic examination revealed lymphangiomyomatosis. The patient survived this rare and potentially fatal disease. We have found no previously published case of bilateral lymphangiomyomatosis treated with separate thoracotomies because of bilateral chylothorax.