Exploring long-term responses to immune checkpoint inhibitors in recurrent and metastatic head and neck squamous cell carcinoma.

OBJECTIVES: Immune checkpoint inhibitors (ICI) have introduced a new era in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Optimal duration for ICI therapy is still unclear and the long-term outcomes and toxicity in patients responding to these therapies warrant further exploration. This study attempts to identify the clinical and biological determinants of a durable response and evaluate outcomes following ICI treatment discontinuation. MATERIALS AND METHODS: A retrospective review of 181 patients treated with ICI for R/M HNSCC was conducted. Long-term responders were defined as patients who sustained disease control at least two years after initiating ICI therapy. We compared clinical and biological characteristics associated with these long-term responders against the broader treatment population. RESULTS: 10 % of R/M HNSCC patients treated with ICIs demonstrated a durable long-term response. Only three relapses (16 %) occurred after discontinuing ICI treatment in this subset, with a median follow-up of 52 months. Upon retreatment with ICI, two attained a documented response. Extended ICI response was observed even with < 2 years of treatment. 74 % of long-term responders experienced immune-related adverse events (irAEs), 37 % of which severe irAEs. Hypothyroidism was the most frequently reported irAEs. The predictive potential of systemic inflammation indices for clinical response appears to be limited. CONCLUSIONS: ICI present an optimistic avenue for HNSCC patients, offering substantial long-term responses. The study suggests that a two-year treatment could be optimal and irAEs, although common, are typically mild.

Can surgically assisted rapid palatal expansion (SARPE) be recommended over orthodontic rapid palatal expansion (ORPE) for girls above the age of 14? : A cone-beam CT study on midpalatal suture maturation.

BACKGROUND: For patients with a maxillary transversal deficiency (MTD), various treatment options are available, partly based on the practitioner's experience. This study aimed to determine a cut-off age for decision making between surgically assisted rapid palatal expansion (SARPE) over orthodontic rapid palatal expansion (ORPE) based on skeletal maturation in a female population. METHODS: A total of 100 cone beam computed tomography (CBCT) images of young females were analyzed on maturation of the pterygomaxillary (PMS), zygomaticomaxillary (ZMS), transpalatal (TPS), and midpalatal (MPS) sutures. Based on the maturation of these four junctions, four independent observers had to determine whether they would prefer ORPE or SARPE to widen the maxilla. RESULTS: For the PMS, the results show a closure of 83-100% from 13 to 17 years. As for the TPS, a closure of 78-85% was observed from 15 years of age. For the 15- to 17-year-old females, a closed ZMS was present in 32-47%. Regarding MPS, closed sutures presented in 61% (stages D and E) of the 15-year-old females. The cut-off age at which SARPE was recommended was 15.1 years for the orthodontist observers and 14.8 years for the maxillofacial surgeon observers. CONCLUSIONS: Significant maturation of MPS was reached at the age of 15 in a female population. The PMS, TPS, MPS, and ZMS closed sequentially. A comprehensive diagnostic approach is necessary for choosing the appropriate treatment. When in doubt, age could assist decision making in a female population, with a cut-off age of 15 years in favor of SARPE based on this study.

Risk of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents - A retrospective study of 240 patients.

This study investigated the incidence, risk factors, and outcome of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents for osteoporosis or bone metastases. 240 patients with a median drug exposure of 43 months were retrospectively studied. The incidence of MRONJ after dental extraction in the osteoporosis cohort was 2.7 % per person-year (95 % CI 1.6-4.6 %) (n = 13/126), and for the bone metastases cohort 26.4 % per person-year (95 % CI 20.4-34.2 %) (n = 58/114). 92 % of MRONJ cases were stage 1. Dental infection as the reason for extraction increased the osteonecrosis risk in the osteoporosis (OR 22.77; 95 % CI 2.85-181.62; p = 0.003) and bone metastases cohorts (OR 2.72; 95 % CI 1.28-5.81; p = 0.010). Using leukocyte and platelet-rich fibrin reduced this risk by 84 % (p = 0.003), as did antibiotics use by 86-93 % (p = 0.013). Within the bone metastases cohort, an interval since last administration of at least 3 months reduced risk of MRONJ (OR 0.83; 95 % CI 0.72-0.97; p = 0.018). Mucosal healing occurred in 11/13 patients (84.6 %; 95 % CI 54.5-98.1 %) with osteoporosis and 31/58 patients (53.4 %; 95 % CI 40.0-66.7 %) with bone metastases. In conclusion, though the MRONJ risk in this selected population taking antiresorptive agents and presenting to the Oral Maxillofacial Surgery clinic for a dental extraction is considerable and higher in those with dental infections, preventive measures such as antibiotics and use of LRPF membranes may significantly reduce that risk.

Tranexamic acid for the prevention and treatment of bleeding in surgery, trauma and bleeding disorders: a narrative review.

OBJECTIVES: We review the evidence for tranexamic acid (TXA) for the treatment and prevention of bleeding caused by surgery, trauma and bleeding disorders. We highlight therapeutic areas where evidence is lacking and discuss safety issues, particularly the concern regarding thrombotic complications. METHODS: An electronic search was performed in PubMed and the Cochrane Library to identify clinical trials, safety reports and review articles. FINDINGS: TXA reduces bleeding in patients with menorrhagia, and in patients undergoing caesarian section, myomectomy, hysterectomy, orthopedic surgery, cardiac surgery, orthognathic surgery, rhinoplasty, and prostate surgery. For dental extractions in patients with bleeding disorders or taking antithrombotic drugs, as well as in cases of idiopathic epistaxis, tonsillectomy, liver transplantation and resection, nephrolithotomy, skin cancer surgery, burn wounds and skin grafting, there is moderate evidence that TXA is effective for reducing bleeding. TXA was not effective in reducing bleeding in traumatic brain injury and upper and lower gastrointestinal bleeding. TXA reduces mortality in patients suffering from trauma and postpartum hemorrhage. For many of these indications, there is no consensus about the optimal TXA dose. With certain dosages and with certain indications TXA can cause harm, such as an increased risk of seizures after high TXA doses with brain injury and cardiac surgery, and an increased mortality after delayed administration of TXA for trauma events or postpartum hemorrhage. Whereas most trials did not signal an increased risk for thrombotic events, some trials reported an increased rate of thrombotic complications with the use of TXA for gastro-intestinal bleeding and trauma. CONCLUSIONS: TXA has well-documented beneficial effects in many clinical indications. Identifying these indications and the optimal dose and timing to minimize risk of seizures or thromboembolic events is work in progress.

The Effect of Smoking on the Postoperative Course After Head and Neck Reconstruction With a Vascularized Free Flap: A Retrospective Study.

OBJECTIVES: The objective of the present study is to determine the impact of smoking on hospital and intensive care unit stay, need for surgical reintervention, Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and morbidity, and surgical complications after head and neck reconstructions. METHODS: All 153 patients who underwent head and neck reconstructions with free tissue transfer at the department of oral and maxillofacial surgery at the University Hospitals of Leuven between January 1, 2015 and December 31, 2018 were enrolled in this retrospective cohort study. Data from medical charts were extracted. Univariate and multiple regression analyses were performed. A level of significance of P < 0.05 (α = 0.05) was used. RESULTS: Smoking was not associated with Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and morbidity, hospital or ICU stay, the incidence of postoperative complications in both flap and donor site, or surgical reintervention. CONCLUSIONS: Regarding the outcomes included in this study, smoking status should not be considered as a critical factor in patient selection for head and neck reconstructions with a vascularized free flap.