Clinical Experience With Gene Therapy in Older Patients With Spinal Muscular Atrophy.

BACKGROUND: Onasemnogene abeparvovec was recently approved for the treatment of spinal muscular atrophy (SMA) in children younger than two years; however, clinical trials were primarily completed in children younger than seven months, so practical experience dosing older children began in summer 2019. Here, we look at the safety and efficacy of onasemnogene in seven infants older than seven months who were treated at our center. METHODS: Seven patients were included. RESULTS: Acute viral symptoms with emesis and/or fever were seen in six of seven patients two to three days after the infusion. Thrombocytopenia occurred in four of seven patients, and six of seven patients had prolonged steroid courses due to persistently elevated liver enzymes, one of whom required escalation to intravenous steroids. All patients demonstrated motor improvements, which were apparent by three months, although with continued progress in those patients followed for longer periods of time. CONCLUSIONS: Overall, onasemnogene appears to be efficacious in children older than seven months and well tolerated. Side effects were similar to those previously reported, although more common and in some cases more severe and more prolonged than seen in the original trials. The impact of age, weight, and other confounding factors on development of side effects still needs to be elucidated.

Fine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital.

We present our experience of fine-needle aspiration (FNA) cytology of the thyroid in a community hospital setting and discuss the cancer probability of the indeterminate FNA results. There were 1,621 FNAs, 401 of which have follow-up thyroidectomies during a 10-yr period. The initial FNA diagnoses of these 401 cases were benign non-neoplastic (BNN) 159, malignant 34, atypical 33, suspicious 19, follicular neoplasm (FN) 88, follicular lesion (FL) 51, and inadequate 17. There were no false-positive cases. Cancer was found in 11 cases diagnosed as BNN (7%), 6 cases were due to sampling errors (incidental microcarcinomas), and 5 cases were due to failure to identify focal atypia in the smears of a follicular variant of papillary carcinoma. The false-negative rate was 3%, with the exclusion of cases of incidental microcarcinomas. Among the indeterminate FNA results, the follow-up operations revealed malignant tumors in 16 of 33 (48%) cases of atypical, 13 of 19 (68%) cases of suspicious, 29 of 88 (33%) cases of FN, and 7 of 51 (14%) cases of FL. Malignant tumors were also found in 2 of 17 (12%) of inadequate specimens with follow-up. When compared to the cancer rate (3%) for FNA diagnosis of BNN, the likelihood of finding cancer in the thyroidectomy is 5 times more for a FL, 11 times more for a FN, 16 times more for atypical, and 23 times more for suspicious. The sensitivity and specificity are 87 and 100%, respectively.

Sensitive cytologic criteria for the identification of follicular variant of papillary thyroid carcinoma in fine-needle aspiration biopsy.

The cytologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) can be extremely challenging and may be associated with false negative diagnoses. The purpose of this study was to determine the minimal cytologic criteria needed to identify FVPTC. We examined sixty-nine fine-needle aspiration (FNA) cases, processed with Diff-Quik and Papanicolaou stains, that were either diagnostic or suspicious of FVPTC. All cases had histologic confirmation. These cases included 29 FVPTC, 18 classic papillary thyroid carcinoma (PTC), 17 follicular neoplasm (6 adenomas, 10 carcinomas, 1 neoplasm NOS), 2 lymphocytic thyroiditis and 3 nodular goiter. Seven of the most commonly cited cytomorphologic features, including flat syncytial sheets, nuclear enlargement, fine chromatin, nuclear grooves, nuclear pseudoinclusions, and amount of colloid and cytoplasm, were evaluated. A diffuse distribution of fine chromatin, nuclear grooves, and colloid was seen more often in FVPTC than in follicular neoplasm (p<0.01). The combination of flat/syncytial sheets, nuclear enlargement, and fine chromatin was observed in all our cases of FVPTC, and is therefore considered a sensitive marker in detecting FVPTC. Logistic regression analysis revealed colloid to be the only positive predictor in favor of FVPTC over classic PTC.