Health-related quality of life in patients with Waldenström macroglobulinemia: results from the ASPEN trial.

Aim ASPEN is a randomized, open-label, Phase III study comparing zanubrutinib and ibrutinib in patients with Waldenström macroglobulinemia (WM). Materials & methods: Patient-reported outcomes were exploratory end points assessed using the EORTC QLQ-C30 and EQ-5D-5L VAS scores. Results: Overall, 201 patients (102 zanubrutinib; 99 ibrutinib) were enrolled. Clinically meaningful differences were observed in diarrhea and nausea/vomiting in both the intent-to-treat population and in patients attaining very good partial response (VGPR) in earlier cycles of treatment, as well as in long-term physical functioning and fatigue in patients achieving VGPR. Conclusion: Treatment with zanubrutinib was associated with greater improvements in health-related quality of life compared with ibrutinib in patients with WM and MYD88 mutations.Clinical Trial Registration: NCT03053440 (ClinicalTrials.gov).

Patient quality of life is importantWhat is this article about? This article talks about a study called the ASPEN trial, which compares two medicines used for treating a rare blood cancer that doctors call Waldenström macroglobulinemia. The medicines are called zanubrutinib (ZAN) and ibrutinib (IBR). They work in the same way, by blocking a protein called Bruton tyrosine kinase. When patients take medicines for an illness, it is important to learn about their physical, social, emotional and mental well-being (quality of life). In this study, we asked patients to fill out questionnaires about their well-being before starting the study treatment for their blood cancer, and again a few times while taking the medication, to see if there were any changes.What were the results of the study? There were two groups of patients. One group took ZAN and the other took IBR. The patients could not choose which medicine they were going to take. Results from both groups of patients were compared. Patients taking ZAN did not feel worse or better about their diarrhea and sickness, but those taking IBR said these symptoms had become worse. Both medicines improved how patients were feeling. However, improvement in tiredness and physical ability was larger in patients taking ZAN than those on IBR, especially for the patients whose cancer was getting better.What do the results mean? For patients with a rare blood cancer in this study, those taking ZAN had a better quality of life than those taking IBR.

Characteristics of ocular injuries associated with mortality in patients admitted with major trauma.

BACKGROUND: Few ocular trauma studies have addressed mortality outcomes. We sought to determine characteristics of mortality-related ocular trauma admissions and compared them with non-fatal injuries. METHODS: A retrospective study was conducted using de-identified data of patients admitted with major trauma from the National Trauma Data Bank (2008-2014). Patients with ocular injury were identified using ICD- 9CM codes. Demographics, intention and mechanism, types of ocular and head injuries, and injury severity were documented. Mortality was determined using post-admission disposition. Statistical analysis using student t-test, chi-square, and odds ratios (OR) calculations were performed with STATA-17 software. Significance was set at P < 0.05. RESULTS: Of 316,485 patients admitted with ocular trauma, 12,233 (3.86%) were mortality related. Expired patients were older than survivors: mean (SD) of 50.1(25.5) vs. 41.5(22.8) years. White (OR = 1.32; P < 0.001), ≥ 65years old (OR = 2.25; P < 0.001), and male (OR = 1.05; P = 0.029) patients were most likely to expire than their counterparts. Common mechanisms of injury in survivors were falls (25.3%), motor vehicle traffic-occupant, MVTO (21.8%) and struck by/against (18.1%) and for fatal injuries, falls (29.7%), MVTO (21.9%) and firearms (11.5%). Traumatic brain injury (TBI) was documented in 88.2% of mortality-related admissions. Very severe injury severity scores (ISS > 24) (OR = 19.19; P < 0.001) and severe Glasgow Coma Score (GCS < 8) (OR = 19.22; P < 0.001) were most associated with mortality than survival. Firearms were most associated with very severe ISS (OR = 3.73; P < 0.001), severe GCS (OR = 4.68; P < 0.001) and mortality (OR = 5.21; P < 0.001) than other mechanisms. Patients with cut/pierce injuries had the greatest odds of survival (OR = 13.48; P < 0.001). Optic nerve/visual pathways injuries (3.1%) had the highest association with very severe ISS (OR = 2.51; P < 0.001), severe GCS (OR = 3.64; P < 0.001) and mortality (OR = 2.58; P < 0.001) than other ocular injuries. Black patients with very severe ISS (OR = 32.14; P < 0.001) and severe GCS (OR = 31.89; P < 0.001) were more likely to expire than other race/ethnicities with similar injury severity. CONCLUSIONS: Mortality-related admissions were older, male, and mostly of White race than ocular trauma admissions of survivors. Firearms were the deadliest mechanism. TBI was commonly associated and patients with optic nerve/pathway injuries, very severe ISS and severe GCS had higher mortality rates. Characteristics and demographic variations identified in this study may be useful in developing focused measures aimed at preventing trauma-related deaths.

Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study.

The phase III ASPEN study demonstrated the comparable efficacy and improved safety of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia (WM). Here, we report long-term follow-up outcomes from ASPEN. The primary end point was the sum of very good partial response (VGPR) + complete response (CR) rates; secondary and exploratory end points were also reported. Cohort 1 comprised 201 patients (myeloid differentiation primary response 88-mutant WM: 102 receiving zanubrutinib; 99 receiving ibrutinib); cohort 2 comprised 28 patients (myeloid differentiation primary response 88 wild-type WM: 28 zanubrutinib; 26 efficacy evaluable). At 44.4-month median follow-up, VGPR + CR rates were 36.3% with zanubrutinib versus 25.3% with ibrutinib in cohort 1 and 30.8% with one CR in cohort 2. In patients with CXC motif chemokine receptor 4 mutation, VGPR + CR rates were 21.2% with zanubrutinib versus 10.0% with ibrutinib (cohort 1). Median progression-free survival and overall survival were not reached. Any-grade adverse events (AEs) of diarrhea (34.7% v 22.8%), muscle spasms (28.6% v 11.9%), hypertension (25.5% v 14.9%), atrial fibrillation/flutter (23.5% v 7.9%), and pneumonia (18.4% v 5.0%) were more common with ibrutinib versus zanubrutinib; neutropenia (20.4% v 34.7%) was less common with ibrutinib versus zanubrutinib (cohort 1). Zanubrutinib was associated with lower risk of AE-related treatment discontinuation. Overall, these findings confirm the long-term response quality and tolerability associated with zanubrutinib.

Osteocyte-Derived CaMKK2 Regulates Osteoclasts and Bone Mass in a Sex-Dependent Manner through Secreted Calpastatin.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

How Ophthalmologists Can Decarbonize Eye Care: A Review of Existing Sustainability Strategies and Steps Ophthalmologists Can Take.

TOPIC: Understanding approaches to sustainability in cataract surgery and their risks and benefits. CLINICAL RELEVANCE: In the United States, health care is responsible for approximately 8.5% of greenhouse gas (GHG), and cataract surgery is one of the most commonly performed surgical procedures. Ophthalmologists can contribute to reducing GHG emissions, which lead to a steadily increasing list of health concerns ranging from trauma to food instability. METHODS: We conducted a literature review to identify the benefits and risks of sustainability interventions. We then organized these interventions into a decision tree for use by individual surgeons. RESULTS: Identified sustainability interventions fall into the domains of advocacy and education, pharmaceuticals, process, and supplies and waste. Existing literature shows certain interventions may be safe, cost-effective, and environmentally friendly. These include dispensing medications at home to patients after surgery, multi-dosing appropriate medications, training staff to properly sort medical waste, reducing the number of supplies used during surgery, and implementing immediate sequential bilateral cataract surgery where clinically appropriate. The literature was lacking on the benefits or risks for some interventions, such as switching specific single-use supplies to reusables or implementing a hub-and-spoke-style operating room setup. Many of the advocacy and education interventions have inadequate literature specific to ophthalmology but are likely to have minimal risks. CONCLUSIONS: Ophthalmologists can engage in a variety of safe and effective approaches to reduce or eliminate dangerous GHG emissions associated with cataract surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Infectious Proctitis due to Human Mpox.

We describe 2 cases of infectious proctitis secondary to human monkeypox in patients presenting with rectal pain. These cases highlight the importance of multidisciplinary management of monkeypox and in expanding case definitions and enabling clinical recognition in patients presenting without skin rash.

Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.

BACKGROUND: Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. METHODS: In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. FINDINGS: Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. INTERPRETATION: Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. FUNDING: None.

Evidence-based Potential Therapeutic Applications of Cannabinoids in Wound Management.

BACKGROUND: Although wound management is a major component of all domains of healthcare, conventional therapeutics have numerous limitations. The endocannabinoid system of the skin, one of the major endogenous systems, has recently been connected to wound healing. Cannabinoids and their interactions with the endogenous chemical signaling system may be a promising therapeutic option because they address some of the fundamental pathways for physiologic derangement that underpin chronic integumentary wounds. RECENT ADVANCES: The therapeutic applications of cannabinoids are increasing because of their legalization and resulting market expansion. Recently, their immunosuppressive and anti-inflammatory properties have been explored for the treatment of wounds that are not effectively managed by conventional medicines. CRITICAL ISSUES: Failure to manage wounds effectively is associated with reduced quality of life, disability, mortality, and increased healthcare expenditures. Therapeutic options that can manage wounds effectively and efficiently are needed. In this review, the authors summarize recent advances on the use of cannabinoids to treat skin disorders with an emphasis on wound management. FUTURE DIRECTIONS: Effective wound management requires medicines with good therapeutic outcomes and minimal adverse effects. Despite the promising results of cannabinoids in wound management, further controlled clinical studies are required to establish the definitive role of these compounds in the pathophysiology of wounds and their usefulness in the clinical setting.

The success of HIV combination prevention: The Dean Street model.

The 56 Dean Street combination prevention model, a strong engagement with the LGBTQI community and flexible services adapted to users' changing needs led to an 80% drop in HIV diagnoses in gay, bisexual and other men who have sex with men (GBMSM) from 2015 to 2017. We describe the service changes at 56 Dean Street since 2012 which resulted in an increase in the frequency of HIV testing, the introduction of pre-exposure prophylaxis, earlier HIV diagnosis and a shorter time to viral suppression in those living with HIV. This model could be adapted to deliver similar results in those settings of high HIV prevalence among GBMSM and where access to technological innovation in healthcare and engagement with the community can be achieved.

Effects of the hangover secret on mitigating hangover symptoms: A pilot study.

BACKGROUND: Due to the popularity of excessive alcohol consumption, there is an increasing need for hangover symptom remedies. Most commercially available hangover treatment products have not been tested for efficacy through clinical study. AIMS: The purpose of this pilot study was to characterize the activity of a commercially available hangover product, The Hangover Secret (THS). METHODS: This was a randomized, double-blinded, placebo-controlled, crossover pilot study. Healthy volunteers of 21- to 40-years-old were eligible for participation, and received either THS or placebo on two different occasions. Participants were given 43 mL of whiskey every twenty minutes for up to 3 hours to achieve a blood alcohol concentration (BrAC) ≥ 0.12%. Hangover severity was assessed using the Acute Hangover Scale (AHS) and Acute Hangover Severity Scale (AHSS) validated tools. RESULTS: Nine participants completed the study. AHS scores increased from baseline to 7 am by 4.11 ± 3.17 and 1.26 ± 2.29 for the placebo and active arms respectively (P = .16). AHS headache scores increased from baseline to 7 am by 2.44 ± 1.67 and 1.11 ± 1.17 for the placebo and active arms respectively (P = .06). AHSS scores increased from baseline to 7 am by 1.0 ± 1.05 and 0.41 ± 1.08, for the placebo and active arms respectively (P = .30). There was no significant difference between average BrAC at 7 am between the placebo and active arms. CONCLUSION: THS showed positive signals in the prevention of alcohol-induced hangover, especially headaches. The improvements with THS surpassed the minimum clinically important difference in overall AHS score and three individual AHS symptoms scores (hangover, headache, and thirsty). THS's reduction in AHS or AHSS scores did not reach statistical significance likely due to the small sample size. Larger studies with appropriate sample sizes are needed in light of these promising findings.

Building Your Brand: Analysis of Successful Oculoplastic Surgeons on Social Media.

PURPOSE: To determine the impact of social media content from oculoplastic surgeon-held accounts on public engagement. METHODS: This study analyzed successful Instagram accounts (defined by >500 followers as of May 2019) held by American Society of Ophthalmic Plastic Reconstruction Surgery members. Each account's 20 most and 20 least successful posts (based on number of likes) were characterized by the post's subject, location, media type, and tag usage. Posts were then analyzed using a web-based application that calculates the engagement level of Instagram users with the selected post. RESULTS: A total of 4,812 posts were analyzed from 37 Instagram accounts. Of these American Society of Ophthalmic Plastic Reconstruction Surgery members, the majority were men (67.6%, n = 25) in private practice solely (70.3%, n = 26). Numerous post characteristics, like content and media type, impacted success in a statistically significant manner; for example, public engagement rose when featuring the posting doctor, especially when smiling and wearing a white coat. Meanwhile, posts featuring an office procedure had a negative effect. Formatting was also found to contribute to success. For example, photographs were preferred over videos, while multiple images were best presented sequentially as a carousel (with the viewer swiping through the series) rather than in a large collage. Use of tags (hashtags, accounts, and locations) were associated with increased engagement. CONCLUSIONS: Social media is an important communication and marketing tool, especially in esthetic fields like oculoplastics. Guidelines for success are presented in this study; content, location, subject, media type, and tags statistically significantly impact public engagement.The influence of social media is rapidly growing and can be strategically harnessed by oculoplastic surgeons to educate both patients and healthcare providers, collaborate with colleagues, and for referrals and marketing.Supplemental Digital Content is available in the text.

The influence of social media is rapidly growing and can be strategically harnessed by oculoplastic surgeons to educate both patients and healthcare providers, collaborate with colleagues, and for referrals and marketing. Supplemental Digital Content is available in the text.

A Case of Docetaxel-Induced Rhabdomyolysis.

Docetaxel is an antimicrotubule agent with activity in a variety of cancers. Its toxicity profile includes myelosuppression, fluid retention/edema, and peripheral neuropathy. It is also associated with myalgias but the frequency and extent of this toxicity are not well described. Here, we present a case of a 48-year-old female with breast cancer who developed bilateral proximal leg pain and inability to walk two weeks after the third cycle of docetaxel and cyclophosphamide. Initial workup showed elevated creatinine kinase (CK) levels which trended up to 9000 U/L suggesting rhabdomyolysis. She was treated with IV isotonic fluids without renal complications. Her CK was 1800 U/L at discharge and normalized two weeks post-discharge. To our knowledge, this is one of the few reports of docetaxel-induced rhabdomyolysis. The purpose of this report is to alert physicians of this rare but morbid complication.

A human cadaveric model for effective instruction of lateral canthotomy and cantholysis.

Purpose: To evaluate a human cadaveric model in improving knowledge and comfort of ophthalmology residents performing a lateral canthotomy/cantholysis.Methods: A prospective study was conducted in ophthalmology residents, who participated in a workshop including an interactive lecture followed by hands-on training on a human cadaver. The lecture consisted of the indications and techniques of lateral canthotomy/cantholysis, along with video-demonstration of proper technique. Residents practiced the procedure on cadavers under faculty supervision. Knowledge and comfort level of conducting the procedure was assessed pre- and post-workshop.Results: Post-workshop, the residents showed a significant improvement in general knowledge regarding the technique of the procedure. Pre-workshop, the average knowledge score was 9 points out of 18 and this improved post-workshop to 12 points out of 18 (p < 0.0001). Residents showed a significant improvement in comfort levels performing the procedure. Using a Likert scale, the average comfort level of performing the procedure rose from 2.5 (Fair) prior to the workshop to 4 (Very Good) post-workshop (p = <0.01). All participants reported an average score of 4.91 (1 = Strongly Disagree, 5 = Strongly Agree) that the human model workshop was clinically applicable to their training and would impact the quality and safety of patient care.Conclusion: The study demonstrated an increase in knowledge and comfort in performing lateral canthotomy and cantholysis using a cadaver model. With the time-sensitive nature of orbital compartment syndrome, it is imperative that physicians are comfortable in performing this procedure to prevent permanent vision loss.

Interventions for orbital lymphangioma.

BACKGROUND: Orbital lymphangiomas are a subset of localized vascular and lymphatic malformations, which most commonly occur in the head and neck region. Orbital lymphangiomas typically present in the first decade of life with signs of ptosis, proptosis, restriction of ocular motility, compressive optic neuropathy, and disfigurement. Therefore, early and effective treatment is crucial to preserving vision. Due to proximity to vital structures, such as the globe, optic nerve, and extraocular muscles, treatment for these lesions is complicated and includes a large array of approaches including observation, sclerotherapy, systemic therapy, and surgical excision. Of these options, there is no clear gold standard of treatment. OBJECTIVES: To assess the evidence supporting medical and surgical interventions for the reduction/treatment of orbital lymphangiomas in children and young adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 5); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 22 May 2018. SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) comparing at least two of the following interventions with each other for the treatment of orbital lymphangiomas: observation; sildenafil therapy; sirolimus therapy; sclerotherapy; surgery (partial or complete resection). We planned to include trials that enrolled children and adults up to 32 years of age, based on a prior clinical trial protocol. There were no restrictions regarding location or demographic factors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles, abstracts, and full articles to assess their suitability for inclusion in this review. No risk of bias or data extraction was performed because we did not find any trials for inclusion. If there had been RCTs, two authors would have assessed the risk of bias and abstracted data independently with discrepancies being settled by consensus or consultation with a third review author. MAIN RESULTS: There were no RCTs that compared any two of the mentioned interventions (medical or surgical) for treating orbital lymphangiomas in children and young adults. AUTHORS' CONCLUSIONS: Currently, there are no published RCTs of orbital lymphangioma treatments. Without these types of studies, conclusions cannot be drawn regarding the effectiveness of the medical and surgical treatment options for patients with orbital lymphangiomas. The presence of only case reports and case series on orbital lymphangiomas makes it clear that RCTs are needed to address the differences between these options and help guide treatment plans. Such trials would ideally compare outcomes between individuals randomized to one of the following treatment options: observation, sclerotherapy, systemic sirolimus therapy, systemic sildenafil therapy, and surgical excision.