Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn’s disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as “failing” standard dosing at 42 weeks who were not dose escalated. Results: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 ( p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL ( p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. Conclusion: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

Patients with cardiac disease frequently develop pleural effusions; the incidence is approximately 500,000 cases per year in the United States. These effusions often represent important clinical events for patients, indicating that either there has been an acute change in the patient's clinical status or the patient's chronic management program needs review. These effusions usually develop in both the right and left hemithorax but can be unilateral. The pathogenesis involves increased fluid transfer from parietal pleural capillaries into the pleural space and possibly decreased pleural fluid uptake into parietal pleural lymphatic structures. The increased fluid transfer develops due to increased capillary pressure secondary to elevated venous outflow pressure and secondary to decreased lymphatic flow into central vessels secondary to heart failure. Most pleural effusions associated with heart failure are transudates, but 20% to 25% have increased protein and lactate dehydrogenase levels suggesting an exudative process. Additional testing can clarify the situation and requires calculation of the serum albumin to pleural fluid albumin gradient or measurement of N-terminal pro-brain natriuretic peptide in the pleural fluid. An albumin gradient of greater than 1.2 g/dL suggests that the fluid is a transudate. The presence of a pleural effusion in a hospitalized patient at discharge is associated with an increased likelihood of rehospitalization and mortality within the next year. Patients with large symptomatic pleural effusions may require therapeutic thoracentesis. Recurrence of symptomatic effusions presents a management dilemma that might require repeated thoracenteses, indwelling intrapleural catheter placement, or other management steps used in advanced chronic heart failure.

Background Studies evaluating the role of midodrine as an adjunctive therapy to liberate patients with shock from intravenous (IV) vasopressors have yielded mixed results. The aim of our study was to evaluate the efficacy and safety of midodrine as an adjunctive therapy to liberate patients with shock from IV vasopressors. Methods Electronic searches of the MEDLINE, EMBASE, and Cochrane databases through April 2022 for randomized controlled trials (RCTs) that evaluated the use of midodrine versus control in patients with shock and a low dose of IV vasopressors. The primary outcome was total IV vasopressor time, while the secondary outcomes included time-to-IV vasopressor discontinuation, IV vasopressor restart, intensive care unit (ICU) length of stay (LOS), hospital LOS, and incidence of bradycardia. Results The final analysis included four RCTs with a total of 314 patients: 158 in the midodrine group and 156 in the control group, with a weighted mean age of 64 years (54.2% men). There was no significant difference in the total IV vasopressor time between the midodrine and control groups (standardized mean difference [SMD] − 0.53; 95% confidence interval [CI] − 1.38 to 0.32, p = 0.22; I 2 = 92%). Also, there were no significant differences between the two groups in the time-to-IV vasopressor discontinuation (SMD − 0.05; 95% CI − 0.57 to 0.47, p = 0.09), IV vasopressor restart (19.3 vs. 28.3%; risk ratio [RR] 0.74; 95% 0.25–2.20, p = 0.59), ICU LOS (SMD − 0.49; 95% CI − 1.30 to 0.33, p = 0.24), and hospital LOS (SMD 0.01; 95% CI − 0.27 to 0.29, p = 0.92). However, compared with the control group, the midodrine group had a higher risk of bradycardia (15.3 vs. 2.1% RR 5.56; 95% CI 1.54–20.05, p = 0.01). Conclusions Among patients with vasopressor-dependent shock, midodrine was not associated with early liberation of vasopressor support or shorter ICU or hospital length of stay. Adding midodrine increased the risk of bradycardia. Further large RCTs are needed to better evaluate the efficacy and safety of midodrine in liberating patients from IV vasopressors. Supplementary Information The online version contains supplementary material available at 10.1007/s40119-023-00301-0.

Sarcomatoid carcinomas, also known as spindle cell carcinomas (SPCCs), are rare carcinomas, predominantly developing in the lung. They have lots of features of sarcoma in their histological features. The standard laryngeal carcinoma classification is based on tumor size, lymph node affection, and metastasis (TNM), it is the classification scheme of the American Joint Committee on Cancer Staging (AJCC), and it is used in the same way for stage spindle cell carcinoma (SPCC). We present a case report of a young female along with a literature review of sarcomatoid carcinoma of the larynx.

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Background Ustekinumab, a monoclonal antibody of interleukin-12 and interleukin-23, was approved for the treatment of moderate to severe Crohn’s disease (CD) in 2016. Ustekinumab is approved in CD for a weight-based IV induction dose followed by every 8 weeks of subcutaneous dosing. Response rates by 6 weeks range from 34% (anti-TNF failures) to 56% in bio-naïve patients. The remainder includes patients who partially-respond (PR) or do not respond (NR). Response by week 16 is 55% (anti-TNF failures) and 73% in bio-naïve patients suggestive of a ‘delayed response’ in some. Experience with anti-TNF drugs demonstrates that a subset of patients respond to dose escalation, which prompts the notion of a potential delayed response phenomenon with Ustekinumab. Aim Determine the efficacy of dose escalation from standard Q8 dosing to Q4 dosing of Ustekinumab in CD patients, who had PR or NR to standard Q8 dosing. Methods A Retrospective observation study of 143 adult patients with CD, on Ustekinumab standard Q8 dosing over a 2 year and 9-month period was conducted. Data was extracted pertaining to demographics, disease, and treatment-related variables (biomarkers, steroid use, interval surgery, ER visits). Patients were further subcategorized as responders, partial responders(PR), and non-responders(NR), based on changes in fecal calprotectin, albumin, CRP, and Physician Global Assessment Disease Severity (1=mild, 2=moderate, 3=severe). Q8 non-responders (NR) and partial responders (PR) were dose-escalated to Q4, and outcome variables were collected. Biomarkers, steroid utilization, interval surgery, and ER visits, and PGA were compared in Q8 partial responder(PR) and non-responders (NR) from the date of starting Ustekinmuab on Q8 dosing to the date of escalation to Q4 dosing, versus the date of escalation Q4 dosing to the end of patient follow up. Results 30% (n=8) of patients were Q8NR, and 70% (n=19) were Q8PR). In the PR group, biomarkers decreased by up to 21% when these patients were switched to Q4 dosing. 100% of patients saw clinical improvement or remained at mild disease on Q4 dosing. In the NR group, biomarkers decreased by up to 91%. 100% of patients saw clinical improvement or remained at mild disease while on Q4 dosing. In both groups, 50% of patients taking steroids on Q8 dosing were no longer taking steroids or were at a reduced dose at the end of Q4 dosing follow-up. 40% of patients on immunomodulators on Q8 dosing were no longer taking immunomodulators at the end of Q4 dosing follow-up. Conclusions

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