Minimally invasive surgical management of primary venous ulcers vs. compression treatment: a randomized clinical trial

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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 (a = 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

Tumor infiltrating lymphocytes in triple negative breast cancer and correlations with prognosis

Following the development of drugs reactivating the immune system, the need to identify immunological markers that can provide prognostic and predictive information is rapidly increasing. This is mainly relevant in triple negative breast cancers, due to their immunogenic potential. Tumor infiltrating lymphocytes (TILs) have been claimed as possible biomarkers of such immune activation, and we investigated their correlation with prognosis

G6PD Ferrara I has the same two mutations as G6PD A(-) but a distinct biochemical phenotype

The cloning and sequencing of the normal glucose-6-phosphate dehydrogenase (G6PD) gene has led to the study of the molecular defects that determine enzymatic variants. In this paper, we describe the mutations responsible for the Ferrara I variant in an Italian man with a family history of favism, from the Po delta. Nucleotide sequencing of this variant showed a G\u2192A mutation at nucleotide 202 in exon IV causing a Val\u2192Met amino acid exchange, and a second A\u2192G mutation at nucleotide 376 in exon V causing an Asn\u2192Asp amino acid substitution. Although on the basis of its biochemical properties this variant was classified as G6PD Ferrara I, it has the same two mutations as G6PD A(-), which is common in American and African blacks, and as the sporadic Italian G6PD Matera. The mutation at nucleotide 202 was confirmed by NlaIII digestion of a polymerase chain reaction amplified DNA fragment spanning 109 bp of exon IV. The 109-bp mutated amplified sequence is not distinguishable from the normal sequence in single strand conformation polymorphism analysis

Therapeutic concentrations of mitotane (o,p'-DDD) inhibit thyrotroph cell viability and TSH expression and secretion in a mouse cell line model.

Mitotane therapy is associated with many side effects, including thyroid function perturbations mimicking central hypothyroidism, possibly due to laboratory test interference or pituitary direct effects of mitotane. We investigated whether increasing concentrations of mitotane in the therapeutic range might interfere with thyroid hormone assays and evaluated the effects of mitotane on a mouse TSH-producing pituitary cell line. TSH, free T(4), and free T(3) levels do not significantly change in sera from hypo-, hyper-, or euthyroid patients after addition of mitotane at concentrations in the therapeutic window. In the mouse TalphaT1 cell line, mitotane inhibits both TSH expression and secretion, blocks TSH response to TRH, and reduces cell viability, inducing apoptosis at concentrations in the therapeutic window. TRH is not capable of rescuing TalphaT1 cells from the inhibitory effects of mitotane on TSH expression and secretion, which appear after short time treatment and persist over time. Our results demonstrate that mitotane does not interfere with thyroid hormone laboratory tests but directly reduces both secretory activity and cell viability on pituitary TSH-secreting mouse cells. These data represent a possible explanation of the biochemical picture consistent with central hypothyroidism in patients undergoing mitotane therapy and open new perspectives on the direct pituitary effects of this drug

Haemodynamic CHIVA correction surgery versus compression for primary venous ulcers: first year results

Objective: To compare two different treatments for primary venous ulcers: a minimally invasive surgical technique for the haemodynamic correction of reflux, versus a traditional compression treatment. Method: From a cohort of 87 lower extremities affected by the first episode of venous ulcers, 45 mobile patients affected by primary chronic venous insufficiency were randomized to receive either the haemodynamic correction procedure (CHIVA) or compression treatment. Results: Mean follow up lasted one year. The rate of healing in the surgical group was 100% in a mean time of 29 days with a velocity of 2.86 mm2/day,and in the conservative group the rate was 96% in 61 days, with a velocity of 1.66 mm2/day (P<0.02). All air plethysmographic parameters, with the exception of ejection fraction, significantly improved at six months in the surgical group. Finally, quality of life significantly improved in both groups, but in the surgical group the following domains were significantly different compared with the compression group: RP, role limitations due to physical problems; VT, energy/vitality; SF, social functioning; RE, role limitations due to emotional problems; and MH, mental health. Conclusions: Surgical haemodynamic correction of reflux has been demonstrated to improve venous function, time to ulcer healing and quality of life when compared with compression treatment