A Case of Wernicke's Encephalopathy Due to Idiopathic Gastroparesis: A Rare Cause of Encephalopathy in a Young Woman.

Wernicke's encephalopathy (WE) is a rare, life-threatening neurological disease due to thiamine deficiency. It is most commonly associated with chronic alcoholism but is also associated with disorders of malabsorption and malnutrition. We present a case of a young female with idiopathic gastroparesis who developed Wernicke's encephalopathy due to poor oral intake and malnutrition as a result of gastroparesis. This case exemplifies that Wernicke's encephalopathy should be on the differential in patients who present with encephalopathy with a history of gastroparesis.

Factors Related to Small- and Mid-Capitalization Pharmaceutical Company Success Using Stock Performance as a Surrogate.

Background Developing novel pharmaceuticals demands substantial investment despite high uncertainty of success and ultimate market value. While many established drug companies are highly profitable and have large portfolios of diversified assets, much of new drug innovation, a very high-risk, high-reward gambit, stems from smaller companies striving to bring their first products to market. While drug costs, and thus pharmaceutical company profits, can be controversial, it is unquestionable that the products from these companies provide great benefit to humanity. Hence, the ongoing success of the industry as a whole is quite relevant from a public health perspective. Methodology We sought to investigate factors influencing pharmaceutical company success using company stock performance on major US indices as a surrogate. As the profitability of large-capitalization (cap) pharmaceutical companies is well established, we focused on small- and mid-cap companies in this analysis. Small- and mid-cap pharmaceutical companies (both currently active and now defunct) and historical share prices were captured, including company details and the nature of drug pipelines. Funding by US academia was acquired via CMS.gov Open Payments and categorized into contributions < or ≥$100,000. Stock performance was considered good (+ ≥25%), mediocre (±25%), or poor (- ≥25%). Univariate and multivariate associations were assessed. Results Of the 420 companies included in the analysis, 101 (24%) had good, 76 (18%) mediocre, and 243 (58%) poor performance. The following were associated with performance in univariate analysis: initial public offering (IPO) price (P < 0.001), time from IPO (P < 0.001), number of drug programs (P = 0.019), and academic funding (P = 0.00013), with trend for diverse pipelines (both oncology and nononcology programs under development) (P = 0.069). On multivariate analysis, IPO price was inversely associated (P < 0.0001), while academic funding (P < 0.0001) and more drug programs (P = 0.0025) were positively associated with performance. Analysis of pharmaceutical IPOs since 2000 suggests a 20% rate of outright company failure. Conclusions The majority of included companies had lackluster stock performance, suggestive of low potential for drug development success and high probability of financial disaster. Robust drug pipelines and academic collaboration seem to be strongly related to company success.

Successful stereotactic radiotherapy of meningiomas in a patient with Cowden syndrome: a case report.

Cowden's Syndrome (CS) is a rare disease with increased risk for several carcinomas. Experimental studies and limited case reports have described the negative effects of radiotherapy. A 35-yearold woman presented with newly diagnosed CS and multiple meningiomas. She underwent subtotal resection of a right petroclival meningioma to relieve brainstem compression and received adjuvant fractionated stereotactic radiotherapy 50 Gy in 25 fractions with minimal side effects. Twenty months post-operatively the patient presented with neurological deficits from progression of additional meningiomas. Craniotomy was performed and gross total resection was achieved for all sites of disease. Imaging five months after surgery demonstrated progressive left tentorial meningioma. She underwent definitive stereotactic radiosurgery to 15 Gy and tolerated treatment well. At 32 and 7 months post-RT, the patient has reported no side effects or toxicity as a result of RT, demonstrating for the first time in the literature, to the best of our knowledge, the use of intracranial RT without significant toxicity in CS.

Risk factors for unplanned readmission in total laryngectomy patients.

OBJECTIVE: To determine which patient or surgical factors affect the likelihood of unplanned readmission (within 30 days) after total laryngectomy (TL). METHODS: Retrospective chart review of all patients who underwent TL at a single institution from April 2007 through August 2016. Primary outcome was unplanned readmission to the hospital within 30 days of discharge. Univariable and multivariable logistic regression were performed to identify risk factors for unplanned readmission. RESULTS: Two hundred seventy-eight patients met inclusion criteria. Twenty-nine patients (10.4%) had unplanned readmissions within 30 days. The most common reasons for readmission were pharyngocutaneous fistula (n = 15), neck abscess (n = 3), and wound breakdown (n = 4). Average time to unplanned readmission was 11.2 days (range 0-27 days). Fistula (OR 30.259; 95% CI, 9.186, 118.147; P ≤ .001), postoperative pneumonia (OR 9.491; 95% CI, 1.783, 53.015; P = .008), and history of cardiac disease (OR 7.074; 95% CI, 2.324, 25.088, P = .001) were independently associated with an increased risk of 30-day unplanned readmission on multivariate analysis. However, return to OR on initial admission was associated with a lower risk of unplanned readmission (OR 0.075; 95% CI, 0.009, 0.402; P = .007). Unplanned readmission was associated with a delay in initiation of adjuvant radiation (OR 1.494; 95% CI, 1.397, 1.599; P < .001). CONCLUSION: Unplanned readmission occurs in a small but significant number of TL patients. Patients who have a 30-day unplanned readmission may be at risk for a delay in initiation of adjuvant therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1725-1732, 2020.

Cesium-131 Interstitial Brachytherapy for Recurrent Malignancies of Skull Base.

Background Recurrent malignancy of the skull base poses a treatment challenge due to a lack of treatment options and potential for damage to surrounding structures. Methods Case report of two patients with recurrent nasopharyngeal carcinoma (NPC) of skull base previously treated with adjuvant chemoradiotherapy using intensity-modulated radiation therapy (IMRT). Results In both cases, the recurrent tumor was treated with endoscopic surgical resection and intraoperative cesium-131 (Cs-131) interstitial brachytherapy (IBT). Total dose delivered to tumor bed was 57 and 60 Gy, respectively. With a half- life of 9 days, the majority of the radiation dose had been delivered within the first 40 days following implant and there have been no treatment-related complications reported. Conclusion Intraoperative Cs-131 IBT is a feasible adjuvant treatment option for patients with recurrent malignancies of the skull base. These are the first known cases of Cs-131 IBT used for recurrent NPC.

Association of Positive Initial Margins With Survival Among Patients With Squamous Cell Carcinoma Treated With Total Laryngectomy.

Importance: Frozen-section analysis of margin status is routinely performed during total laryngectomy for squamous cell carcinoma; in the case of positive initial frozen margins, re-resection to negative margins can often be accomplished. Some evidence suggests that positive initial margins may be associated with worse survival among patients with head and neck cancer even when final margins are negative, but the significance of positive initial frozen margins in total laryngectomy is poorly understood. Objective: To determine the association between disease-free survival and positive initial margins among patients treated with total laryngectomy for squamous cell carcinoma. Design, Setting, and Participants: In this retrospective cohort study conducted at a tertiary care center, records of 237 consecutive patients treated with total laryngectomy for squamous cell carcinoma from February 2008 to July 2016 were reviewed for demographic characteristics, disease staging, pathologic markers, and outcomes. Margins were considered to be positive if they contained invasive carcinoma, carcinoma in situ, or severe dysplasia. Data analysis was performed from March to June 2018. Interventions: All patients had undergone total laryngectomy for squamous cell carcinoma. Main Outcomes and Measures: Variables associated with disease-free survival were analyzed using a univariable and multivariable Cox proportional hazards model. Results: Among all 225 patients (184 [92%] male; mean age, 63.9 years; range, 30-92 years) who underwent total laryngectomy and had negative final margins, 127 patients underwent primary total laryngectomy and 98 underwent salvage total laryngectomy, with mean (SEM) follow-up of 29.3 (1.8) months. Initial frozen margins were positive in 40 of 225 patients (18%); positive initial margins occurred in 21 of 127 patients who underwent primary total laryngectomy (17%) and in 19 of 98 patients who underwent salvage total laryngectomy (19%). On multivariable analysis, only salvage laryngectomy was associated with significantly worse disease-free survival (hazard ratio [HR], 3.35; 95% CI, 1.76-6.36). Among 98 patients who underwent salvage total laryngectomy, positive lymph nodes, lymphovascular invasion, extracapsular nodal extension, and adjuvant therapy were associated with worse disease-free survival on univariable analysis, but no factors remained significant on multivariable analysis. Among 127 patients who underwent primary total laryngectomy, positive nodes, lymphovascular invasion, extracapsular nodal extension, and positive initial margins were associated with worse disease-free survival; however, only positive initial margins were associated with significantly worse disease-free survival on multivariable analysis (HR, 5.01; 95% CI, 1.55-16.2). Conclusions and Relevance: In this study, positive initial margins were associated with worse disease-free survival among patients who underwent primary total laryngectomy despite negative margins on final pathologic examination. This finding may indicate aggressive tumor behavior in the context of primary laryngeal squamous cell carcinoma.