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Abstract Background Amyloidosis is defined by abnormal protein folding and subsequent deposition in tissues. Cardiac involvement is usually related to misfolded monoclonal immunoglobulin light chains or misfolded transthyretin; however, apolipoprotein A-1–associated amyloidosis is a hereditary form of amyloidosis resulting from mutations in the AAPOA1 gene that can also result in cardiac amyloidosis. Although there have been advancements in noninvasive algorithms for the diagnosis of cardiac amyloidosis, endomyocardial biopsy (EMB) may still be warranted. All individuals undergoing EMB are susceptible to complications, including tricuspid valve injury resulting in severe tricuspid valve regurgitation. Case summary Our patient is a 70-year-old white man presented with symptoms of dyspnoea on exertion and decreased functional capacity, diagnosed previously with apolipoprotein A-I cardiac amyloidosis, confirmed by EMB. He developed progressive right-sided heart failure secondary to iatrogenic flail tricuspid leaflet related to the diagnostic EMB. He underwent a successful transcatheter tricuspid valve edge-to-edge repair with 4D intracardiac echocardiographic guidance. At the recent follow-up, the patient showed improved symptoms, with increased stamina, and transoesophageal echocardiography revealed a 65% ejection fraction and mild tricuspid regurgitation (TR). Discussion Tricuspid valve injury is one of the complications associated with EMB, which can result in severe TR. Transcatheter tricuspid valve edge-to-edge repair can be a useful option for patients considered too high risk for surgical intervention, such as those with advanced cardiac amyloidosis.

Abstract The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

Abstract Objectives Healthcare institutions implement antimicrobial stewardship (AMS) programmes to optimize the use of antibiotics. The focus is often on inpatient rather than outpatient settings. We aimed to explore perceptions of AMS stakeholders on effective interventions for appropriate antibiotic use in outpatient settings, and the role of clinical pharmacists in the AMS multidisciplinary team. Methods A qualitative semi-structured interview study using thematic analysis by two researchers independently. Participants that practice AMS programmes were recruited from healthcare facilities in the United Arab Emirates (UAE). Interviews were conducted face to face or online and transcribed verbatim. Results Four themes emerged: (i) Perceived factors leading to unnecessary or inappropriate antibiotic prescribing and their impact on patients and the community; (ii) current outpatient AMS activities and perceived barriers and facilitators for their sustainability; (iii) suggested outpatient AMS strategies to be implemented in outpatient settings; and (iv) perceived future AMS implementation barriers and suggested mitigation strategies. Conclusions Several AMS interventions, together with the presence of a clinical pharmacist, may be effective in improving antibiotic use in UAE outpatient settings. Future research should investigate the most appropriate AMS strategy considering barriers and possible mitigation strategies to ensure sustainability.

ImportanceLip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.ObjectiveTo analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence ReviewThe incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.FindingsIn 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and RelevanceIn this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Introduction: There is an increasing interest in cold snare endoscopic mucosal resection (CS-EMR), and studies have shown its safety and efficacy for colonic polyps. This meta-analysis aims to assess the safety and efficacy of CS-EMR for the removal of duodenal adenomas. Methods: We conducted a comprehensive literature search of several databases, from inception through February 2023, for studies that addressed outcomes of CS-EMR for nonampullary duodenal adenomas. We used the random-effects model for the statistical analysis. The weighted pooled rates were used to summarize the technical success, polyp recurrence, bleeding, and perforation events. Cochran Q test and I 2 statistics adjudicated heterogeneity. Results: Six studies were included in the analysis. In all, 178 duodenal polyps were resected using CS-EMR. The pooled rates were 95.8% (95% CI 89.1–98.5%, I 2=21.5%) for technical success and 21.2% (95% CI 8.5–43.6%, I 2=78%) for polyp recurrence. With regards to CS-EMR safety, the pooled rates were 4.2% (95% CI 1.6–10.5%, I 2=12%) for immediate bleeding, 3.4% (95% CI 1.5–7.6%, I 2=0%) for delayed bleeding, 2.8% (95% CI 1.1–6.7%, I 2=0%) for perforation, and 2% (95% CL 0.5–7.5%, I 2=0%) for post-polypectomy syndrome. Rates were not significantly different for large adenomas. Three studies reported data on CS-EMR and conventional EMR. Compared with conventional EMR, CS-EMR had lower odds of delayed bleeding, OR 0.11 (CI 0.02–0.62, P value 0.012, I 2=0%). Conclusion: Our findings suggest that CS-EMR is a safe and effective strategy for the resection of nonampullary duodenal adenomas, with an acceptable recurrence rate. Data from larger randomized controlled studies are needed to validate our findings.

Background Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR. Methods We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. I2 statistics were used to evaluate heterogeneity. Results 4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %–17.4 %, I2 = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %–35.7 %, I2 = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %–46.7 %, I2 = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %–9.9 %, I2 = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %–4.5 %, I2 = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %–2.7 %, I2 = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %–1.3 %, I2 = 0 %) and 0.6 % (95 %CI 0.3 %–1.4 %, I2 = 0 %), respectively. Conclusion CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.

Background The analgesic effectiveness of contemporary motor-sparing nerve blocks used in combination for analgesia in total knee arthroplasty is unclear. This network meta-analysis was conducted to evaluate the analgesic effectiveness of adding single-injection or continuous adductor canal block (ACB) with or without infiltration of the interspace between the popliteal artery and the capsule of the posterior knee (iPACK) to intraoperative local infiltration analgesia (LIA), compared to LIA alone, after total knee arthroplasty. Methods Randomized trials examining the addition of single-injection or continuous ACB with or without single-injection block at the iPACK to LIA for total knee arthroplasty were considered. The two primary outcomes were area-under-the-curve pain scores over 24 to 48 h and postoperative function at greater than 24 h. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 h; opioid consumption (from 0 to 24 h and from 25 to 48 h); and incidence of nausea/vomiting. Network meta-analysis was conducted using a frequentist approach. Results A total of 27 studies (2,317 patients) investigating the addition of (1) single-injection ACB, (2) continuous ACB, (3) single-injection ACB and single-injection block at the iPACK, and (4) continuous ACB and single-injection block at the iPACK to LIA, as compared to LIA alone, were included. For area-under-the-curve 24- to 48-h pain, the addition of continuous ACB with single-injection block at the iPACK displayed the highest P -score probability (89%) of being most effective for pain control. The addition of continuous ACB without single-injection block at the iPACK displayed the highest P -score probability (87%) of being most effective for postoperative function. Conclusions The results suggest that continuous ACB, but not single-injection ACB and/or single-injection block at the iPACK, provides statistically superior analgesia when added to LIA for total knee arthroplasty compared to LIA alone. However, the magnitude of these additional analgesic benefits is clinically questionable. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Introduction: Post-transcatheter aortic valve replacement (TAVR) outcome of patients is an important research topic. To accurately assess post-TAVR mortality, we examined a family of new echo-parameters (augmented systolic blood pressure (AugSBP) and arterial mean pressure parameters (AugMAP)) derived from blood pressure and aortic valve gradient ( Figure 1 ). Methods: Patients in the Mayo Clinic National Cardiovascular Diseases Registry-TAVR database who underwent TAVR between January 1, 2012, and June 30, 2017, were identified to retrieve baseline clinical, echocardiographic, and mortality data. The median of AugSBP and AugMAP were used to stratify patients in Kaplan-Meier analysis. Results: The final cohort contained 974 patients with a mean age of 81.4±8.3 years old, and 56.6% were male. The mean Society of Thoracic Surgeons risk score was 8.2±5.2. The median follow-up duration was 354 days, and the one-year all-cause mortality rate was 14.2%. Detailed characteristics are summarized in Table 1. AugMAP1 < 102.5 mmHg (median) was associated with a 3-fold risk of all-cause mortality post-TAVR at 1 year (hazard ratio 3.0, 95%confidence interval 2.0-4.5, p<0.0001)( Figure 1 ). Conclusions: Augmented mean arterial pressure provides clinicians with a simple but effective approach to quickly identify patients at risk and potentially improve post-TAVR prognosis.

Despite advances in treatment, outcomes remain poor for patients with penta-relapsed refractory multiple myeloma (RRMM). In this retrospective analysis, we evaluated the survival outcomes of penta-RRMM patients treated with (BCMA)- directed therapy (BDT). We identified 78 patients with penta-RRMM. Median age was 65 years, 29 (37%) had R-ISS stage III disease, 63 (81%) had high-risk cytogenetics, and 45 (58%) had extra-medullary disease. Median LOT prior to penta-refractory state was 5 (3–12). Amongst penta-RRMM, 43 (55%) were treated with BDT, 35 (45%) were not treated with BDT. Type of BDT received included belantamab mafadotin 15 (35%), Chimeric Antigen Receptor T-cell therapy 9 (21%), BCMA monoclonal antibody 6 (14%), and Bispecific T-cell engager 2 (5%). Eleven (25%) patients received more than one BDT. No significant differences were identified between baseline characteristics for the two groups. Patients treated with a BDT had better median overall survival, 17 vs. 6 months, HR 0.3 p-value < 0.001. Poor performance status, white race, and high-risk cytogenetics were associated with worse outcomes, whereas using a BDT was associated with better outcomes. Patients with penta-refractory MM have poor outcomes. Our retrospective analysis showed a significant survival benefit using BDT when compared to non-BDT for patients with penta-RRMM.

Abstract The Omicron variant was first detected in October 2021, which evolved from the original SARS‐CoV‐2 strain and was found to possess many mutations. Immune evasion was one of the notable consequences of these mutations. Despite Omicron exhibiting increased transmissibility, the rates of hospitalizations and deaths among patients infected with this variant were substantially lower when compared to other strains. However, concluding that the Omicron variant is less severe than other variants of SARS‐CoV‐2 requires consideration of multiple factors, including the vaccination status of infected patients as well as any previous infections with other variants. This review compiled data about any reported indicators of severity in Omicron‐infected patients, including studies comparing Omicron with other variants while adjusting for confounders. A comprehensive search was conducted using different databases to target any studies about Omicron. In total, 62 studies met our inclusion criteria and were included in this study. Many studies reported a significantly reduced risk of hospitalization, ICU admission, need for oxygenation/ventilation, and death in Omicron‐infected patients compared to patients infected with other variants, such as Delta. Some studies, however, reported comparable severity in Omicron infected patients as to other variants emphasizing a substantial risk for severe illness. Furthermore, the COVID‐19 vaccines were less effective against Omicron relative to previous lineages, except after receiving the booster dose. One study recommended vaccination during pregnancy, which may help prevent future cases of severe SARS‐CoV‐2 pneumonia in neonates and young infants due to the transfer of humoral response from the mother.