Mucormycosis after CD19 chimeric antigen receptor T-cell therapy: results of a US Food and Drug Administration adverse events reporting system analysis and a review of the literature.

Chimeric antigen receptor (CAR) T-cell therapy leads to durable remissions in relapsed B-cell cancers, but treatment-associated immunocompromise leads to a substantial morbidity and mortality risk from atypical infection. Mucormycosis is an aggressive and invasive fungal infection with a mortality risk of 40-80% in patients with haematological malignancies. In this Grand Round, we report a case of mucormycosis in a 54-year-old patient undergoing CAR T-cell therapy who reached complete clinical control of Mucorales with combined aggressive surgical debridement, antifungal pharmacotherapy, and reversal of underlying risk factors, but with substantial morbidity from extensive oro-facial surgery affecting the patient's speech and swallowing. For broader context, we present our case alongside an US Food and Drugs Administration adverse events reporting database analysis and a review of the literature to fully evaluate the clinical burden of mucormycosis in patients treated with CAR T-cell therapy. We discuss epidemiology, clinical features, diagnostic tools, and current frameworks for treatment and prophylaxis. We did this analysis to promote increased vigilance for mucormycosis among physicians specialising in CAR T-cell therapy and microbiologists and to illustrate the importance of early initiation of therapy to effectively manage this condition. Mucormycosis prevention and early diagnosis, through targeted surveillance and mould prevention in patients at highest risk and Mucorales-specific screening assays, is likely to be key to improving outcomes in patients treated with CAR T-cell therapy.

Incidental Thyroid Tissue in Sentinel Nodes From Oral Squamous Cell Carcinoma.

OBJECTIVE: Sentinel node biopsy (SNB) is a surgical staging test in which sentinel nodes (SNs) undergo intensive histological analysis. SNB diagnoses early cancer spread, but can also reveal unexpected findings within the SNs. We review cases of incidental thyroid cells (TC) found in SNs from patients with oral squamous cell carcinoma (OSCC) to assess the prevalence of TC, and the clinical significance of these. METHODS: Multicenter retrospective review of SNB performed for cT1-T2N0 OSCC. Incidental TC were identified by TTF-1 or thyroglobulin positivity. Anatomical location of nodes containing TC, TC morphology, and ongoing management/follow up of this incidental finding was recorded. Neck dissections performed during the same period were reviewed to establish the expected incidence of TC in neck nodes without serial sectioning analysis. RESULTS: 278 SNB cases were reviewed. Ten procedures detected TC in nine patients (10/278, 3.6%). During the same time period 725 neck dissections were performed, six containing TCs (6/725, 0.8%). One patient underwent SNB twice with TC identified on both occasions. Three patients had both OSCC metastasis and thyroid cells. All SNB patients with TC identified underwent thyroid USS with no primary tumours identified. Three patients underwent thyroidectomy, in all cases no primary thyroid tumour was found. CONCLUSION: Prevalence of incidental TC in SNs appears to be higher than that reported in neck dissections, these are not likely to be clinically relevant and can be managed on a conservative basis in the absence of clear metastatic features. LEVEL OF EVIDENCE: Multicentre retrospective cohort study, 3 Laryngoscope, 134:1278-1281, 2024.

An Unusual Case of Ludwig's Angina Following Mandibular Fracture.

The mandible is the most commonly fractured bone in the maxillofacial region following trauma. Severe infections are rare, and so we highlight an unusual presentation of Ludwig's angina following a late presentation of a mandibular fracture in a 68-year-old gentleman with significant medical co-morbidities. The recovery process was prolonged and involved multi-disciplinary input. This case makes a recommendation for early recognition of mandibular fractures, antibiotic therapy where appropriate, and hypervigilance when caring for patients with systemic illnesses.

Transient femoral neuropathy after harvest of bone from the iliac crest.

A 31-year-old woman had bone harvested from the left anterior iliac crest as a graft for an augmentation genioplasty. For postoperative analgesia, she was given a bupivacaine infusion into the iliac wound. She developed a temporary left femoral mononeuropathy from which she recovered completely.

Influence of close resection margins on local recurrence and disease-specific survival in oral and oropharyngeal carcinoma.

There is a lack of consistency among published reports in the definition of what constitutes close resection margins (1-5mm) in the surgical treatment of oral and oropharyngeal squamous cell carcinoma (SCC). Our aim was to define what would constitute close resection margins in predicting local recurrence and disease-specific survival. The study comprised 192 previously untreated patients with oral and oropharyngeal SCC who were recruited at the Southern General Hospital, Glasgow, from 2001 to 2007 with a minimum follow-up of 2 years. Resection was the primary treatment and the surgical margins were recorded for all patients. Statistical analyses were aided by the Statistical Package for the Social Sciences, version 15.0, and MedCalc software. The status of the surgical margins was evaluated using a receiver operating characteristic (ROC) curve to define the cut-off point. Cox's proportional hazard model was used to establish predictive factors for local recurrence and disease-specific survival. Of 192 patients, 23 (12%) had involved margins (<1.0mm), 107 (56%) had close margins (1.0-2.0mm (16.1%); 2.1-3.0mm (12%); 3.1-4.0mm (10.4%); 4.1-5.0mm (17.2%), and 62 (32.3%) had clear margins (>5mm). No predictive cut-off point was found that related close surgical margins to local recurrence. However, there was a significant adverse association between surgical margins ≤1.6mm and disease-specific survival. In recommending postoperative adjuvant treatment for oral and oropharyngeal SCC, we suggest that surgical margins within 2mm should be considered as the cut-off. However, other clinical and pathological prognostic factors should also be taken into consideration when recommending further treatment.

Use of Lugol's iodine in the resection of oral and oropharyngeal squamous cell carcinoma.

We evaluated the use of Lugol's iodine in achieving surgical margins free from dysplasia, carcinoma in situ, and invasive carcinoma by an observational study of two series of 50 consecutive patients having resection of oral and oropharyngeal squamous cell carcinoma (SCC) between November 2004 and March 2007. The standard group had resection of the primary tumour with a macroscopic 1cm margin and removal of adjacent visibly abnormal mucosa. The Lugol's iodine group had identical treatment with resection of any adjacent mucosa that did not stain after the application of Lugol's iodine (where this was feasible). In the standard group 16 patients (32%) had dysplasia, carcinoma in situ, or invasive SCC at a surgical margin. In the Lugol's iodine group two patients (4%) had dysplasia or carcinoma in situ; none had invasive SCC. Lugol's iodine is a simple, inexpensive, and apparently effective means of reducing the likelihood of unsatisfactory surgical margins in the resection of oral and oropharyngeal SCC.