Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial.

BACKGROUND: This study investigated the efficacy of chemoradiotherapy (CRT) followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer. PATIENTS AND METHODS: The PANDORA trial is a prospective, phase II, open-label, single-arm, multicenter study aimed at evaluating the efficacy and safety of preoperative treatment with durvalumab (1500 mg every 4 weeks for three administrations) following long-course radiotherapy (RT) plus concomitant capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine administered at 825 mg/m2 twice daily). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the proportion of clinical complete remissions and safety. The sample size was estimated assuming a null pCR proportion of 0.15 and an alternative pCR proportion of 0.30 (α = 0.05, power = 0.80). The proposed treatment could be considered promising if ≥13 pCRs were observed in 55 patients (EudraCT: 2018-004758-39; NCT04083365). RESULTS: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were assessable for the study's objectives. Two patients experienced disease progression during treatment. Nineteen out of 55 eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation). CONCLUSION: This study met its primary endpoint showing that CRT followed by durvalumab could increase pCR with a safe toxicity profile. This combination is a promising, feasible strategy worthy of further investigation.

Emergency contraception: a review.

Emergency contraceptives (EC) are forms of contraception that women can use after intercourse to prevent pregnancy. EC use is safe for women of all ages, and there are no medical contraindications to its use. There are two types of emergency contraceptive pills currently available: ulipristal acetate (UPA) and levonorgestrel. UPA is the most effective oral option for EC. In the United States, levonorgestrel containing ECPs are available without prescription to women and men without age restrictions. However, the more effective UPA pills require a prescription. ECPs do not cause abortion or harm an established pregnancy. Placement of a copper intrauterine device (IUD) is more effective EC than either UPA or levonorgestrel, and requires a timely visit with a trained clinician. EC pills are less effective for women who are overweight or obese, therefore such women should be offered a copper IUD or ulipristal rather than levonorgestrel pills. Any woman requesting EC after unprotected intercourse should be offered treatment within 120 hours of intercourse, as should all women who are victims of sexual assault. Women requesting EC should be offered information and services for ongoing contraception. Although levonorgestrel EC is now available over-the-counter, ongoing need exists to educate women about emergency contraception to encourage prompt use of EC when it is needed.

Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer.

BACKGROUND: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model. METHODS: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models. RESULTS: The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215-0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370-0.891), progression-free survival after first-line CT ≥ 6 months (P=0.027; HR, 0.633; 95% CI 0.422-0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392-0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001). CONCLUSIONS: Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design.

[Atrial defibrillators or implantable atrioverters. Initial results]. / Défibrillateur auriculaire ou atrioverteur implantable. Premiers résultats.

The atrial defibrillator is a new non-pharmacological treatment of atrial fibrillation (AF) for restoration of sinus rhythm. This device has two programmable modes: automatic or activated by the physician or patient. In the automatic mode, the device delivers a shock synchronous with the R wave to restore sinus rhythm when AF is detected. Two patients with paroxysmal AF resistant to pharmacological therapy were included in a study to assess the efficacy and safety of the atrial defibrillator in the mode activated by the physician. The device implanted in the pectoral region is connected to 3 electrodes, two for atrial defibrillation and sensing positioned in the coronary sinus and right atrium respectively and a sensing and pacing electrode in the right ventricle. The right ventricle is paced if a post-shock pause is detected. It is possible to interrogate the device with a programmer using its Holter function and so determine the number of episodes of AF sensed and treated. The number, intensity and energy of the shocks and the parameters of ventricular stimulation are programmable. In these two patients, the atrial defibrillator effectively reduced prolonged episodes of AF with a follow-up of 12 and 7 months. No pro-arrhythmic effects were observed. Further clinical evaluation is under way to assess this new mode of treatment, including the mode activated by the patient, safety and tolerance of the shocks. In our two patients, the treatment of prolonged episodes of AF was followed by reduction of many short or asymptomatic episodes.

Compliant vs non-compliant balloons. A prospective randomized study.

In this prospective randomized trial we explored the possibility of different procedural outcomes with regard to compliant (polyolefin copolymer (POC)), and non-compliant (polyethylene terapthelate (PET)) balloon materials commonly used during percutaneous transluminal coronary angioplasty (PTCA). For this purpose, 51 female and 149 male (total 200) patients were randomized to 100 compliant and 100 non-compliant balloons. Only single lesions were included in the study and patients who had PTCA for more than one lesion in different segments at different sessions were each entered separately (there were actually 49 female and 143 male patients). PTCA procedures were performed in conjunction with quantitative coronary angiographic techniques and the films were reviewed by two investigators in a blinded fashion. Statistical analysis for various procedural end-points were performed by non-paired Student t test with statistical significance being p < 0.05. There were no differences in demographic and clinical characteristics between groups. Lesion characteristics of both groups were exactly matching for vessel size, balloon size, balloon vessel ratio, minimal luminal diameter and percent stenosis of the index lesion. Similarly, minimal residual diameter, percent residual stenosis, net gain, densitometric net area gain, and maximum pressure (2.2 +/- 5 mm vs 2.1 +/- 0.6 mm, 18 +/- 17% vs 23 +/- 15%, 0.8 +/- 0.5 mm vs 0.8 +/- 0.6 mm, 48 +/- 25% vs 48 +/- 26%, 7.3 +/- 2 atm. vs 6.8 +/- 3 atm., respectively) values were not statistically different between compliant and non-compliant balloon groups. Major in-hospital complications, dissections caused by the study balloon (mostly type A and B), crossover and bail-out procedures (5 vs 3, 34 vs 32, 4 vs 3, 13 vs 14, respectively) were similar for both compliant and non-compliant balloon groups. Study balloon success rate (defined as < 50% residual stenosis or > 20% net gain in the absence of major in-hospital complications, crossovers and bail-outs) and overall procedural success rate (80% vs 74%, 90% vs 85%) were not statistically different for compliant and non-compliant balloons. In conclusion, we did not observe any statistically significant difference between compliant and non-compliant balloons in terms of immediate procedural results.

Directional coronary atherectomy versus coronary angioplasty in vessels larger than 3 mm in diameter.

It has been proposed that directional coronary atherectomy (DCA) should be an intervention of choice in larger vessels as one can achieve a greater minimal luminal diameter with DCA than with percutaneous transluminal coronary angioplasty (PTCA). This in turn should translate into a higher success rate and may even reduce the restenosis rate. The aim of this study was to compare DCA versus PTCA in vessels > 3 mm in diameter. One hundred fifty consecutive patients who met the inclusion criteria and had DCA were compared to 150 similarly selected PTCA patients. PTCA patients were selected from the era immediately preceding the advent of DCA so that selections bias could be excluded. All patients with ostial lesions, restenosis, vessels < 3 mm in diameter, and vessels with more than two significant lesions were excluded. Distal segments and circumflex cases were excluded as they formed a small subsegment. Both groups were similar in terms of demographic, clinical and angiographic variables. Quantitative analysis showed that the initial net gain was significantly greater in the DCA group than in the PTCA group (2.36 +/- 0.8 mm vs. 1.78 +/- 0.7 mm; p < 0.05). Residual stenosis was 11% with DCA compared to 33% with PTCA (p < 0.05). Despite these improved anatomical results the procedural success rates were similar (91.5% vs 84%). Major in hospital complications (death, acute occlusion, MI, emergency CABG, re-do) were higher in the DCA group than in the PTCA group (12% vs 6%). Clinical follow-up on 276 patients (150 DCA vs 126 PTCA) showed a 6 month clinical restenosis rate of 18% vs 28%, respectively. The incidence of re-do in 24 hours for acute occlusion was 6% for DCA and 1% for PTCA. In large-sized vessels DCA results in a lower restenosis rate. However, despite a lower incidence of residual stenosis, the complication rate tends to be higher with DCA (p < 0.05).

A new method for evaluating the effect of antiarrhythmic drugs on atrioventricular nodal conduction.

Electrophysiological variables were studied in 19 patients before and after one of three commonly used antiarrhythmic agents. The pacing rate at which alternating Wenckebach periods appeared in eight patients was significantly reduced by intravenous digoxin (0.01 mg/kg body weight). The atrioventricular nodal conduction time (A-H interval) and Wenckebach point were not significantly altered by digoxin. Intravenous propranolol (0.1 mg/kg body weight) in four patients did not affect the A-H interval, but it reduced the pacing rates at which the Wenckebach point and alternating Wenckebach periods occurred. Intravenous disopyramide (2 mg/kg body weight) significantly increased the pacing rate required to produce alternating Wenckebach periods but did not significantly alter the other indicators of atrioventricular conduction in seven patients. It is concluded that the pacing rate required to produce alternating Wenckebach periodicity may be a useful and sensitive variable in the evaluation of the effect of antiarrhythmic agents on atrioventricular nodal conduction.

Percutaneous transluminal coronary angioplasty after previous coronary artery bypass surgery.

To improve symptomatic status and avoid repeat coronary artery bypass graft surgery (CABG), 115 lesions were approached for transluminal coronary angioplasty (PTCA) in 94 patients (82 men, 12 women) with angina pectoris and prior CABG at a mean of 60 months (range 4 to 192) after CABG. Fifteen patients were in Canadian Cardiovascular Society functional class I, 32 were in class II, 31 were in class III, and 16 were in class IV. Patients were 37 to 76 years old (mean 57). PTCA was successful (at least a 40% reduction in stenosis diameter and improvement in symptomatic status) in 83 patients (88%) and 103 (90%) lesions. Mean stenosis was reduced from 80 +/- 14% to 20 +/- 16% (mean +/- standard deviation) and mean pressure gradient from 41 +/- 7 mm Hg to 14 +/- 6 mm Hg. Seven patients had lesions that could not be crossed for technical reasons and these patients underwent non-emergency CABG. Four patients required emergency CABG after PTCA; 1 patient subsequently died and 2 survived acute myocardial infarction. One patient had a femoral artery laceration, which required surgical repair. At a mean follow-up of 8 +/- 4 months, 63 patients (76%) with initially successful results were free of angina or in improved condition. Of the remaining 20 patients, 18 consented to repeat coronary angiography. Four patients did not have restenosis. Of the 14 patients with documented restenosis, 5 underwent successful repeat PTCA, 5 had repeat CABG, and 4 were treated medically. Thus, when coronary anatomy is suitable, PTCA is an effective alternative to reoperation in symptomatic patients with prior CABG.

Retrograde (ventriculoatrial) conduction.

Interest in retrograde VA conduction has been renewed with the advent of tachycardias induced by physiologic pacemakers with atrial sensing capabilities. Accurate representation of ventriculoatrial conduction requires detailed electrophysiologic analysis during sinus rhythm, during tachycardias whether or not associated with accessory pathways, and during ventricular pacing studies. Retrograde conduction should be assessed in patients considered for implantation of atrial sensing and tracking pacemakers (VAT, VDD, DDD), until technologic advances overcome the problems of endless loop tachycardias.