TNF-Alpha Inhibitors and Ustekinumab for the Treatment of Psoriasis: Therapeutic Utility in the Era of IL-17 and IL-23 Inhibitors

Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and comorbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

Hematologic manifestations of SARS-CoV-2 infection and MIS-C in hospitalized children. Results of the PICNIC registry.

Introduction: Hematologic complications of SARS-CoV-2 infection are well described in hospitalized adults with correlation to adverse outcomes. Information published in children has been limited. Methods: An international multi-centered retrospective registry was established to collect data on the clinical manifestations of SARS-CoV-2 or multisystem inflammatory syndrome (MIS-C) in hospitalized children between February 1, 2020 – May 31, 2021. This sub-study focused on hematologic manifestations. Study variables included patient demographics, comorbidities, clinical presentation, course, laboratory parameters, management, and outcomes. Results: Nine hundred and eighty-five children were enrolled and 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection upon admission, 288 had MIS-C (31.4%) and 242 (26.4%) had alternate diagnosis with SARS-CoV-2 identified incidentally. During hospitalization, 10 children (1%) experienced a thrombotic event, 16 (1.7%) had hemorrhage and 2 (0.2%) had both thrombotic and hemorrhagic episodes. Significant prothrombotic comorbidities included congenital heart disease (p-value = 0.007), central venous catheter (p = 0.04) in children with primary SARS-CoV-2 infection; and obesity (p-value= 0.002), cytokine storm (p= 0.012) in those with MIS-C. Significant pro- hemorrhagic conditions included age > 10 years (p = 0.04), CVC (p= 0.03) in children with primary SARS-CoV-2infection; and thrombocytopenia (0.001), cytokine storm (0.02) in those with MIS-C. Eleven patients died (1.2 %) with no deaths attributed to thrombosis or hemorrhage Conclusion: Thrombotic and hemorrhagic complications are uncommon in children with SARS-CoV-2 infection and observed with underlying co-morbid conditions. Understanding the complete spectrum of hematologic complications in children with SARS-CoV-2 infection or MIS-C requires ongoing multi-center studies.

On the receiving end: have patient perceptions of the side-effects of cancer chemotherapy changed since the twentieth century?

Background Studies in 1983 and 1993 identified and ranked symptoms experienced by cancer patients receiving chemotherapy. We repeated the studies to obtain updated information on patient perceptions of chemotherapy-associated symptoms. Patients and methods A cross-sectional interview and patient-reported outcome questionnaires were administered to out-patients receiving chemotherapy. Patients selected from 124 cards to identify and rank the severity of physical and non-physical symptoms they had experienced and attributed to chemotherapy (primary endpoint). The patient’s medical oncologist and primary chemotherapy nurse were invited to rank the five symptoms they believed the patient would rank as their most severe. We analysed the association of symptoms and their severity with patient demographics, chemotherapy regimen, and patient-reported outcomes. Results were compared to the earlier studies. Results Overall, 302 patients completed the interview: median age 58 years (range 17–85); 56% female; main tumour types colorectal 81 (27%), breast 67 (22%), lung 49 (16%); 45% treated with curative intent. Most common symptoms (reported by >50%) were: alopecia, general weakness, effects on family/partner, loss of taste, nausea, fatigue, difficulty sleeping, effects on work/home duties, and having to put life on hold. The most severe symptoms (ranked by >15% in top five) were: concern about effects on family/partner, nausea, fear of the future, fatigue, not knowing what will happen, putting my life on hold, and general weakness. Perceptions of doctors and nurses of patients’ symptom severity closely matched patients’ rankings. Conclusions Compared to earlier studies, there was an increase in non-physical concerns such as effects on family and future, and a decrease in physical symptoms, particularly vomiting, but nausea, fatigue and general weakness remained bothersome. Highlights • Symptoms related to chemotherapy have changed over time, likely due to less toxic regimens and improvements in supportive care. • Effects on family/partner, fear of the future, not knowing what will happen, and “life on hold” were major issues for patients. • Vomiting has decreased but nausea, fatigue and general weakness remain common symptoms for chemotherapy patients.

Nasobiliary drainage: an effective treatment for pruritus in cholestatic liver disease

IntroductionNasobiliary drains (NBDs) have been successfully used to manage intrahepatic cholestasis, bile leaks and obstructive cholangitis. It allows external drainage of bile, bypassing the ileum where bile salts are reabsorbed. We assessed the utility of placement with effect on markers of cholestasis and patient symptoms.MethodsConsecutive patients undergoing NBD over 12 years for the management of pruritus were retrospectively analysed. Recorded variables included patient demographics, procedural characteristics and response to therapy.ResultsTwenty-three patients (14, 61% male) underwent 30 episodes of NBD. The median age was 26 years old (range 2–67 years old). A single procedure was carried out in 20. One patient each had two, three and five episodes of NBD. The most common aetiologies were hereditary cholestatic disease (n=17, 74%) and drug-induced cholestasis (n=5, 22%),NBD remained in situ for a median of 8 days (range 1–45 days). Significant improvement in bilirubin was seen at 7 days post-NBD (p=0.0324), maintained at day 30 (335 μmol/L vs 302 µmol/L vs 167 µmol/L). There was symptomatic improvement in pruritus in 20 (67%, p=0.0494) episodes. One patient underwent NBD during the first trimester of pregnancy after medical therapy failure with a good symptomatic response. The catheters were well tolerated in 27 (90%) of cases. Mild pancreatitis occurred in 4 (13%) cases.ConclusionNBD can be used to provide symptomatic improvement to patients with pruritus associated with cholestasis. It is well tolerated by patients. They can be used in pregnancy where medical management has failed.

Age Demographics of Subjects Enrolled in Global, Interventional Phase 3 Melanoma Clinical Trials

Background Melanoma is a skin cancer with a rising worldwide incidence of just over 280,000 individuals with the greatest burden of illness in European, New Zealander, and Australian populations. Patients are diagnosed with melanoma with the mean and median ages being 65 and 59 years old, respectively. Phase 3 trials not only provide a wide representation of the target population but also study the efficacy for a certain intervention. Objective The objective of this literature review is to analyze patient demographics of phase 3 trials for melanoma and identify if there is a true disparity between the clinical trial age demographics and the natural epidemiological age demographics. Data Sources The authors conducted a search on clinicaltrials.gov, a publicly available resource that lists clinical trials and their data. The reported mean and median ages for each trial were extracted after determining if each trial meets our inclusion criteria. Weighted mean and median ages were calculated using an online calculator. Data Summary Data from 35 trials were evaluated with 30 trials reporting a weighted mean age of 55.85 years and 5 trials reporting a weighted median age of 55.14 years. Conclusion Based on the results, melanoma clinical trials enroll patients who are younger than the epidemiological mean and median ages. Due to this underrepresentation of the elderly patients with melanoma, clinical trials may provide limited application for the use of their results.

Management and Outcomes of Bilateral Acetabular Fractures: A Critical Review of the Literature

Background Bilateral acetabular fractures constitute a rare entity, and their optimal management is unknown. Materials and Methods A systematic literature search was conducted in PubMed, Embase and Cochrane Library between 1995 and 2020. Inclusion criteria were studies presenting cases of bilateral acetabular fractures and reporting outcomes. Extracted data included patient demographics, injury mechanism, fracture classification, associated injuries, management and outcomes. Results Thirty-seven studies (47 cases; 35 males vs 12 females) were included. Mean age was 46 years old (range 13–84) and mean follow-up was 19.8 months (range 1.5–56). High-energy injuries (49%) and seizures (45%) were the most common injury mechanisms. Fracture type distribution differed according to injury mechanism. Treatment was surgical in 70% of cases (75% open reduction and internal fixation vs 25% acute total hip arthroplasty). Outcomes were excellent/good in 58% of patients. Complications included heterotopic ossification (11%), nerve injury (11%), degenerative arthritis (6%), DVT (6%), and infection (3%). Conclusions Bilateral acetabular fractures most commonly occur either after trauma or seizures and are commonly managed operatively. They are not devoid of complications, however, more than half (58%) achieve complete functional recovery.

The Impact of Clinical Practice Guidelines on Preoperative Antibiotic Administration for Carpal Tunnel Release

Background: In 2015, the American Association of Plastic Surgeons (AAPS) published a consensus statement against the routine use of preoperative antibiotic prophylaxis to prevent surgical site infection in clean hand surgery. The American Academy of Orthopaedic Surgeons (AAOS) similarly cited “insufficient evidence” in its Appropriate Use Criteria guidelines to support the use of antibiotics in carpal tunnel surgery. Nonetheless, its administration remains a common practice during clean hand surgery. We sought to evaluate the impact of the above guidelines on preoperative antibiotic administration. Methods: An institutional review board–approved retrospective chart review of consecutive patients with carpal tunnel syndrome treated with open carpal tunnel release (CTR) at our institution was performed in the 2 years before and after publication of AAPS/AAOS guidelines. Patient demographics and surgical outcomes were reviewed. Incidence of antibiotic administration, patient demographics, and surgeon factors were collected. Results: A total of 770 primary open CTR procedures were performed in the studied years. In 2013 and 2014, 83.9% of patients received preoperative antibiotics. In 2017 and 2018, 48.2% of patients received preoperative antibiotics. Of the variables analyzed, immunosuppression, history of diabetes, and poorly controlled diabetes (A1c > 7) were found to be statistically significant in its positive correlation to prophylactic preoperative antibiotic use. Diabetes was not associated with surgical site infections. Conclusion: Patients were more likely to receive preoperative antibiotics before the publication of the AAPS/AAOS clinical practice guidelines. Patients with diabetes regardless of their glycemic control are more likely to receive preoperative antibiotics.

An ACS-NSQIP Analysis of Unicompartmental Knee Arthroplasty Trends from 2013 to 2018

Unicompartmental knee arthroplasty (UKA) volume has increased with advances in implant design, perioperative protocols, and patient selection. This study analyzed national trends of UKA from 2013 to 2018 and the relationship between patient demographics and postoperative outcomes. Data on UKA (CPT 27446) from 2013 to 2018 was collected from the National Surgical Quality Improvement Program (NSQIP). Variables collected included patient demographics, American Society of Anesthesiology classification, functional status, NSQIP morbidity probability, operative time, length of stay, 30-day reoperation, and readmission rates. There was an increase in outpatient UKAs performed (920 in 2013; 11,080 in 2018) (p < 0.0001). Analysis of variance from 2013 to 2018 revealed significant decrease in patient body mass index (BMI) (32.5 in 2013; 31.5 in 2018) (p < 0.01) and NSQIP morbidity probability (0.014 in 2013; 0.011 in 2018) (p < 0.0001). Operative time increased (79.1 minutes in 2013; 84.4 minutes in 2018) (p < 0.01), but length of stay decreased (0.9 days in 2013; 0.5 days in 2018) (p < 0.0001). The number of all-cause and related readmissions decreased significantly (p < 0.045; p < 0.01). Age, male gender, BMI >40 and chronic obstructive pulmonary disease (COPD) were significant predictors for 30-day readmission. BMI >40 was a significant predictor for discharge destination. UKA has seen a rise in incidence from 2013 to 2018 with an increasing number of outpatient UKAs. Operative times and 30-day readmissions have both decreased in this time. BMI > 40 is predictive for discharge destination after UKA, while age, male gender, BMI >40, and COPD are independent risk factors for 30-day readmission.