Rejected

Tegaserod (Zelnorm®) is a 5-hydroxytryptamine (serotonin) type 4 receptor agonist for the treatment of hypomotility disorders of the lower gastrointestinal tract associated with the irritable bowel syndrome with constipation (IBS-C).

Pudendal neuralgia is a painful neuropathic condition involving the pudendal nerve dermatome. Tarlov cysts have been reported in the literature as another potential cause of chronic lumbosacral and pelvic pain. Notably, they are often located in the distribution of the pudendal nerve origin at the S2, S3, and S4 sacral nerve roots and it has been postulated that they may cause similar symptoms to pudendal neuralgia. Literature has been inconsistent on the clinical relevance of the cysts and if they are responsible for symptoms.

To study the presentation, management strategies and long-term natural history of children with pancreatic trauma.

Background and Purpose- Studies on the prevalence and risk factors of white matter lesions (WMLs) in Tibetans living at high altitudes are scarce. We conducted this study to determine the prevalence and risks of WMLs in Tibetan patients without or with nonacute stroke. Methods- We undertook a retrospective analysis of medical records of patients treated at the People's Hospital of Tibetan Autonomous Region and identified a total of 301 Tibetan patients without acute stroke. WML severity was graded by the Fazekas Scale. We assessed the overall and age-specific prevalence of WMLs and analyzed associations between WMLs and related factors with univariate and multivariate methods. Results- Of the 301 patients, 87 (28.9%) had peripheral vertigo, 83 (27.3%) had primary headache, 52 (17.3%) had a history of stroke, 36 (12.0%) had an anxiety disorder, 29 (9.6%) had epilepsy, 12 (4.0%) had infections of the central nervous system, and 3 (1.0%) had undetermined diseases. WMLs were present in 245 (81.4%) patients, and 54 (17.9%) were younger than 40 years. Univariate analysis showed that age, history of cerebral infarction, hypertension, the thickness of the common carotid artery intima, and plaque within the intracarotid artery were related risks for WMLs. Ordered logistic analysis showed that age, history of cerebral ischemic stroke, hypertension, male sex, and atrial fibrillation were associated with WML severity. Conclusions- Risk factors for WMLs appear similar for Tibetans residing at high altitudes and individuals living in the plains. Further investigations are needed to determine whether Tibetans residing at high altitudes have a higher burden of WMLs than inhabitants of the plains.

Silent thyrotropin pituitary adenomas (TSHomas) are defined by absence of hyperthyroidism despite TSH immunopositivity. Data pertaining to clinical and surgical characteristics of silent TSHomas remains limited. We aim to describe the clinical presentation, pathological characteristics, and outcomes in silent TSHoma patients treated at a tertiary pituitary center. We retrospectively identified patients with histologically-proven silent TSHoma who underwent transsphenoidal resection at our center between 2000 and 2016 (n = 1244 total patients). Patients with preoperative hyperthyroidism or thyroidectomy were excluded. Twenty patients with silent TSHomas were included (1.6% of surgically treated PAs), of which 35% were reoperations. Presenting symptoms included vision loss (45%) and headache (40%). Preoperative pituitary dysfunction included hypothyroidism (40%), hypogonadotropic hypogonadism (30%), and panhypopituitarism (15%). Nineteen patients (95%) had macroadenomas (mean diameter 29.9 mm). Extrasellar growth was identified in 17 patients (85%) and 65% had cavernous sinus invasion. Immunostaining for alpha-subunit was positive in 19 patients (95%), and 75% of tumors expressed immunopositivity for hormones other than TSH. Gross total tumor resection was achieved in 9 patients (45%) on follow-up MRI. Major postoperative complications included hydrocephalus (1 patient) and cerebrospinal fluid leak with meningitis (1 patient). Tumor progression and recurrence occurred in 1 patient each (10% total) over the follow-up period (median 18.5 months). Silent TSHomas tend to be large, invasive tumors. In addition to TSH, a majority express immunopositivity for alpha-subunit and gonadotropins, thereby potentially supporting a primitive adenoma lineage and subtype. Despite reoperation in several patients, good overall outcomes with low complication rates were achieved.

CD19-targeted chimeric antigen receptor modified T-cell immunotherapy (CAR-T cell therapy) is a novel treatment with promising results in patients with relapsed/refractory lymphoid malignancies. CAR-T cell therapy has known early toxicities of cytokine release syndrome (CRS) and neurotoxicity, but little is known about long-term neuropsychiatric adverse effects. We have utilized patient-reported outcomes (PROs), including PROMIS® measures, to assess neuropsychiatric and other patient-reported outcomes of 40 patients with relapse/refractory chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL), one to five years after treatment with CD19-targeted CAR-T cells. Mean T scores of PROMIS domains of Global Mental health, Global Physical Health, Social Function, anxiety, depression, fatigue, pain and sleep disturbance were not clinically meaningfully different from the mean in the general US population. However, 19 patients (47.5%) reported at least one cognitive difficulty and/or clinically meaningful depression and/or anxiety, and 7 patients (17.5%) scored ≤ 40 in Global Mental Health, indicating at least one standard deviation worse than the general population mean. Younger age was associated with worse long-term Global Mental Health (p=0.02), anxiety (p=0.001) and depression (p=0.01). Anxiety prior to CAR-T cell therapy was associated with increased likelihood of anxiety after CAR-T cell therapy (p=0.001). 15 patients (37.5%) reported cognitive difficulties post CAR-T cell therapy. Depression prior to CAR-T cell therapy was statistically significantly associated with higher likelihood of self-reported post CAR-T cognitive difficulties (p=0.02) and there was a trend for association between acute neurotoxicity and self-reported post-CAR-T cognitive difficulties (p=0.08). Having more post-CAR-T cognitive difficulties was associated with worse Global Mental Health and Global Physical Health. Our study demonstrates overall good neuropsychiatric outcomes in 40 long-term survivors after CAR-T cell therapy. However, nearly 50% of patients in the cohort reported at least one clinically meaningful negative neuropsychiatric outcome (anxiety, depression or cognitive difficulty), indicating that there is a significant number of patients who would likely benefit from mental health services following CAR-T cell therapy. Younger age, pre-CAR-T anxiety or depression, and acute neurotoxicity may be risk factors for long-term neuropsychiatric problems in this patient population. Larger studies are needed to confirm these findings.