Thursday, January 19, 2023

Risk of Myocardial Infarction, Ischemic Stroke, and Mortality in Patients Who Undergo Gastric Bypass for Obesity Compared With Nonoperated Obese Patients and Population Controls

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imageObjective: The aim of this study was to estimate risks of myocardial infarction, ischemic stroke, and cardiovascular-related and all-cause mortality after Roux-en-Y gastric bypass (RYGB) for obesity compared with nonop-erated obese patients and matched nonobese population controls. Background: Few studies have assessed the influence of RYGB on fatal and non-fatal myocardial infarction and ischemic stroke, and the results vary between studies. Method: All patients aged 20 to 65 years with obesity diagnosis in the nationwide Swedish Patient Registry in 2001 to 2013 were included. These participants were divided into those who underwent RYGB within 2 years of obesity diagnosis (n = 28,204) and nonoperated (n = 40,827), and were matched for age, sex, and region with 2 nonobese population controls. Participants were followed until onset of outcome disease, death, or end of follow-up. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI). Results: Compared with nonoperated patients with obesity, RYGB patients had a reduced risk of myocardial infarction [HR = 0.44 (95% CI 0.28-0.63)], similar risk of ischemic stroke [HR = 0.79 (95% CI 0.54–1.14)], and decreased risks of cardiovascular-related [HR = 0.47 (95% CI 0.35–0.65)] and all-cause mortality [HR = 0.66 (95% CI 0.54–0.81)] within the first 3 years of follow-up, but not later. Compared with nonobese population controls, RYGB patients had excess risks of ischemic stroke [HR = 1.57 (95% CI 1.08–2.29)], cardiovascular-related mortality [HR = 1.82 (95% CI 1.29–2.60)], and all-cause mortality [HR = 1.42 (95% CI 1.16–1.74)], but not of myocardial infarction [HR = 1.02 (95% CI 0.72–1.46)]. Conclusion: RYGB for obesity might not decrease the risk of ischemic stroke, but seems to decrease the risk of myocardial infarction back to population levels.
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Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology, quality of life, and radiographic response

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Abstract

Background

Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel–Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM.

Procedure

A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed.

Results

Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus.

Conclusion

Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.

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Monkeypox virus, herpes simplex virus and cytomegalovirus skin coinfections

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Abstract

We read with interest the recent article entitled "Concomitant diagnosis of sexually transmitted infections and human monkeypox in patients attending a sexual health clinic in Milan, Italy" by Rizzo et al

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Inhibition of influenza A virus replication by a marine derived quinolone alkaloid targeting virus nucleoprotein

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Abstract

Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, a novel quinolone alkaloid (QLA) derived from marine fungus was discovered with broad-spectrum anti-IAV activities with low toxicity. Distinct from current anti-IAV drugs, QLA may block virus replication and viral RNA (vRNA) export from the nucleus by targeting virus nucleoprotein (NP). QLA can block the binding of chromosome region maintenance 1 (CRM1) to nuclear export signal 3 (NES3) of NP to inhibit the nuclear export of NP and vRNP. QLA may also affect vRNP assembly by interfering with the binding of NP to RNA rather than NP oligomerization. Arg305 and Phe488-Gly490 may be required for the interaction between QLA and NP, and the binding pocket around these amino acids may be a promising target for anti-IAV drugs. Importantly, oral administration of QLA can protect the mice against IAV-induced d eath and weight loss, superior to the effects of the clinical drug oseltamivir. In summary, the marine derived compound QLA has the potential to be developed into a novel anti-IAV agent targeting virus NP protein in the future.

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Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction

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Osseointegration and Bone Resorption of Scapula Tip Free Flaps in Mandibular Reconstruction

Few studies have shown significant bone resorption over time in scapula free flaps for mandibulectomy defects. Our series show high rates of osseous union and limited bone resorption that is equivalent to other vascularized osseous flaps.


Objectives

Bone resorption of more conventional vascularized bone grafts have been well described showing minimal resorption over time. Few studies have evaluated osseous union and bone resorption in scapula tip free flaps (STFF) in the reconstruction of mandibulectomy defects. We aimed to describe our series on STFF with respect to osseous union and bone resorption over time.

Methods

Retrospective chart review of patients receiving STFF from January 2014–January 2017 (n = 25). A neuroradiologist analyzed follow-up CT scans to assess (1) STFF complete, partial, or no osseous union with native mandible and (2) STFF volume change over time in a subset with multiple follow-up scans (n = 18).

Results

Twenty-three of 25 patients (92%) showed complete or partial STFF osseous union with native mandible either distally or proximally. STFF volume change ranged from +4.8 to −54% (median −0.5%) over median follow-up interval of 23 months. History of chemoradiation therapy, bisphophonate use, sex, age, or smoking history did not correlate with bone resorption.

Conclusions

STFFs shows high rates of osseous union and limited bone resorption that is equivalent to, or less than, vascularized fibular and iliac crest flaps. Clinically, this translates into both optimal healing and functional and cosmetic outcomes, especially in the setting of prior therapies.

Level of Evidence

4 Laryngoscope, 2023

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The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis

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The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis

A systematic review and meta-analysis was done to characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP). The addition of HPV vaccination was associated with an increase in time between surgeries, and reduced the number of surgical procedures required for patients with RRP. HPV vaccination may be a beneficial adjuvant treatment for RRP.


Objective

To characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP).

Data Sources

PubMed, Embase, Cochrane, Google Scholar, ClinicalTrials.gov, and Web of Science databases were queried for articles published before April 2021.

Review Methods

All retrieved studies (n = 870) were independently analyzed by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement using predefined inclusion and exclusion criteria. 13 studies met inclusion criteria. A random-effects meta-analysis was performed to study intersurgical interval (ISI) and number of surgical procedures per year before and after vaccination.

Results

The systematic review included 13 studies, comprising 243 patients. All studies utilized the Gardasil® quadrivalent vaccine, and one study (Yiu et al. 2019) utilized both the quadrivalent and Gardasil® 9-valent vaccines. Our meta-analysis included 62 patients with ISI data across 4 studies, and 111 patients with data on the number of surgical procedures per month across 7 studies. The mean number of surgical procedures decreased by 4.43 per year after vaccination (95% CI, −7.48 to −1.37). Mean ISI increased after vaccination, with a mean difference of 15.73 months (95% CI, 1.46–29.99). Two studies reported on HPV sero-conversion, with HPV seropositivity of 100% prior to vaccination and 25.93% after vaccination.

Conclusion

The addition of HPV vaccination was associated with an increase in time between surgeries and reduction in the number of surgical procedures required. HPV vaccination may be a beneficial adjuvant treatment for RRP.

Level of Evidence

N/A Laryngoscope, 2023

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Carolyn's Window Approach to Unilateral Frontal Sinus Surgery

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Carolyn's Window Approach to Unilateral Frontal Sinus Surgery

Carolyn's window approach aims to remove the limitation created by the anterior-posterior depth to make a Draft 2a frontal sinusotomy easier for the surgeon. The approach is a 0° endoscope technique and provides an excellent view of the frontal sinus and recess.


Objectives

Due to the complexity and variety of the frontal recess and sinus anatomy, traditional Draf 2a frontal sinus surgery is challenging. The thickness of the nasofrontal beak and anterior–posterior dimensions of the frontal recess contribute to this complexity. Carolyn's window technique eliminates the limitation of anterior–posterior depth to facilitate a Draf 2a frontal sinusotomy. The approach is a 0° endoscope technique and provides an excellent view of the frontal sinus and recess. We describe Carolyn's window approach to frontal sinus surgery and the perioperative outcomes.

Methods

Consecutive adult patients in whom Carolyn's window technique was applied for frontal sinus dissection as part of the endoscopic management of both inflammatory and neoplastic disease were assessed. The primary outcome was frontal sinus patency. Secondary outcomes were surgical morbidity, defined as early (<90 days) or late (>90 days).

Results

Forty-five patients (49.1 ± 17.9 years, 48.9% Female) were assessed. All patients had successful frontal sinus patency (100% [95CI: 92.1%–100%]). Morbidities were adhesion (4.8%), crusting (2.4%), pain (1.2%), and bleeding (1.2%) in the early postoperative period. There were no other morbidities in the early and late postoperative periods.

Conclusion

Carolyn's window approach to frontal sinusotomy is a technique that evolves from previously described approaches. Successful frontal sinus patency with very low morbidities is achieved while still working with a 0° endoscope. The "axillectomy" performed simplifies frontal recess surgery by removing the anteroposterior diameter limitation and the dexterity required in angled endoscopy and instrumentation. The inferior-based lateral wall mucosal flap and free mucosal grafting expedite the mucosal healing process. Laryngoscope, 2023

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Practitioner Review: It's time to bridge the gap – understanding the unmet needs of consumers with attention‐deficit/hyperactivity disorder – a systematic review and recommendations

alexandrossfakianakis shared this article with you from Inoreader

Objective

Understanding the unmet needs of healthcare consumers with attention-deficit/hyperactivity disorder (ADHD) (individuals with ADHD and their caregivers) provides critical insight into gaps in services, education and research that require focus and funding to improve outcomes. This review examines the unmet needs of ADHD consumers from a consumer perspective.

Methods

A standardised search protocol identified peer-reviewed studies published between December 2011 and December 2021 focusing on consumer-identified needs relating to ADHD clinical care or research priorities.

Results

1,624 articles were screened with 23 studies that reviewed examining the needs of ADHD consumers from Europe, the U.K., Hong Kong, Iran, Australia, the U.S.A. and Canada. Consumer-identified needs related to: treatment that goes beyond medication (12 studies); improved ADHD-related education/training (17 studies); improved access to clinical services, carer support and financial assistance (14 studies); school accommodations/support (6 studies); and ongoing treatment efficacy research (1 study).

Conclusion

ADHD consumers have substantial unmet needs in clinical, psychosocial and research contexts. Recommendations to address these needs include: improving access to and quality of multimodal care provision; incorporating recovery principles into care provision; fostering ADHD health literacy; and increasing consumer participation in research, service development and ADHD-related training/education.

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Role of Angiotensin Receptor Blockers in the context of Alzheimer’s Disease

alexandrossfakianakis shared this article with you from Inoreader

Abstract

As the world's population ages, the prevalence of age-related neurological disorders such as Alzheimer's disease (AD) is increasing. There is currently no treatment for Alzheimer's disease, and the few approved medications have a low success rate in lowering symptoms. As a result, several attempts are underway worldwide to identify new targets for the therapy of Alzheimer's disease. In pre-clinical studies of Alzheimer's disease, it was recently found that inhibition of angiotensin-converting enzyme (ACE) and blocking of the angiotensin II receptors reduce symptoms of neurodegeneration, Aβ plaque development, and tau hyperphosphorylation. Angiotensin II type I (AT1) blockers, such as telmisartan, candesartan, valsartan, and others, have a wide safety margin and are commonly used to treat hypertension. Renal and cardiovascular failure are reduced due to their vascular protective actions. Inhibition of AT1 receptors in the brain has a neuroprotective impact in humans, reducing the risk of stroke, increasing cognition, and slowing the progression of Alzheimer's disease. The review focuses on the mechanisms via which AT1 blockers may act beneficially in Alzheimer's disease. Although their effect is evident in pre-clinical studies, clinical trials, on the other hand, are in short supply to validate the strategy. More dose-response experiments with possible AT1 blockers and brain-targeted administration will be needed in the future.

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Comparative effectiveness of different primary vaccination courses on mRNA-based booster vaccines against SARs-COV-2 infections: a time-varying cohort analysis using trial emulation in the Virus Watch community cohort

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
The Omicron B.1.1.529 variant increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in doubly vaccinated individuals, particularly in the Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1) recipients. To tackle infections, the UK's booster vaccination programmes used messenger ribonucleic acid (mRNA) vaccines irrespective of an individual's primary course vaccine type, and prioritized the clinically vulnerable. These mRNA vaccines included the Pfizer–BioNTech COVID-19 vaccine (BNT162b2) the Moderna COVID-19 vaccine (mRNA-1273). There is limited understanding of the effectiveness of different primary vaccination courses on mRNA booster vaccines against SARs-COV-2 infections and how time-varying confounders affect these evaluations.
Methods
Trial emulation was applied to a prospective community observational cohort in England and Wales to reduce time-varying confounding-by-indication driv en by prioritizing vaccination based upon age, vulnerability and exposure. Trial emulation was conducted by meta-analysing eight adult cohort results whose booster vaccinations were staggered between 16 September 2021 and 05 January 2022 and followed until 23 January 2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end of study was modelled using Cox proportional hazard models and adjusted for age, sex, minority ethnic status, clinically vulnerability and deprivation.
Results
A total of 19 159 participants were analysed, with 11 709 ChAdOx1 primary courses and 7450 BNT162b2 primary courses. Median age, clinical vulnerability status and infection rates fluctuate through time. In mRNA-boosted adults, 7.4% (n = 863) of boosted adults with a ChAdOx1 primary course experienced a SARS-CoV-2 infection compared with 7.7% (n = 571) of those who had BNT162b2 as a primary course. The pooled adjusted hazard ratio (aHR) was 1.01 with a 95% confidence interval (CI) of: 0.90 to 1.13.
Conclusion
After an mRNA booster dose, we found no difference in protection comparing those with a primary course of BNT162b2 with those with a ChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection.
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