Amyloid Transthyretin Cardiomyopathy in Elderly Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Background The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to determine the prevalence of ATTR-CM in patients with severe aortic stenosis and evaluate differences in presentations and outcomes of patients with concomitant ATTR-CM undergoing transcatheter aortic valve implantation. Methods and Results Prospective screening for ATTR-CM with Technetium99-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy was performed in 315 patients referred with severe aortic stenosis between August 2019 and August 2021. Myocardial Technetium99-3,3-diphosphono-1,2-propanodicarboxylic acid tracer uptake was detected in 34 patients (10.8%), leading to a diagnosis of ATTR-CM in 30 patients (Perugini ≥2: 9.5%). Age (85.7±4.9 versus 82.8±4.5; P=0.001), male sex (82.4% versus 57.7%; P=0.005), and prior carpal tunnel surgery (17.6% versus 4.3%; P=0.007) were associated with coexisting ATTR-CM, as were ECG (discordant QRS voltage to left ventricular wall thickness [42% versus 12%; P<0.001]), echocardiographic (left ventricular ejection fraction 48.8±12.8 versus 58.4±10.8; P<0.001; left ventricular mass index, 144.4±45.8 versus 117.2±34.4g/m2; P<0.001), and hemodynamic parameters (mean aortic valve gradient, 23.4±12.6 versus 35.5±16.6; P<0.001; mean pulmonary artery pressure, 29.5±9.7 versus 25.8±9.5; P=0.037). Periprocedural (cardiovascular death: hazard ratio [HR], 0.71 [95% CI, 0.04-12.53]; stroke: HR, 0.46 [95% CI, 0.03-7.77]; pacemaker implantation: HR, 1.54 [95% CI, 0.69-3.43]) and 1-year clinical outcomes (cardiovascular death: HR, 1.04 [95% CI, 0.37-2.96]; stroke: HR, 0.34 [95% CI, 0.02-5.63]; pacemaker implantation: HR, 1.50 [95% CI, 0.67-3.34]) were similar between groups. Conclusions Coexisting ATTR-CM was observed in every 10th elderly patient with severe aortic stenosis referred for therapy. While patients with coexisting pathologies differ in clinical presentation and echocardiographic and hemodynamic parameters, peri-interventional risk and early clinical outcomes were comparable up to 1 year after transcatheter aortic valve implantation. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT04061213.

Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial.

Importance: Left ventricular remodeling following acute myocardial infarction results in progressive myocardial dysfunction and adversely affects prognosis. Objective: To investigate the efficacy of paroxetine-mediated G-protein-coupled receptor kinase 2 inhibition to mitigate adverse left ventricular remodeling in patients presenting with acute myocardial infarction. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial was conducted at Bern University Hospital, Bern, Switzerland. Patients with acute anterior ST-segment elevation myocardial infarction with left ventricular ejection fraction (LVEF) of 45% or less were randomly allocated to 2 study arms between October 26, 2017, and September 21, 2020. Interventions: Patients in the experimental arm received 20 mg of paroxetine daily; patients in the control group received a placebo daily. Both treatments were provided for 12 weeks. Main Outcomes and Measures: The primary end point was the difference in patient-level improvement of LVEF between baseline and 12 weeks as assessed by cardiac magnetic resonance tomography. Secondary end points were changes in left ventricular dimensions and late gadolinium enhancement between baseline and follow-up. Results: Fifty patients (mean [SD] age, 62 [13] years; 41 men [82%]) with acute anterior myocardial infarction were randomly allocated to paroxetine or placebo, of whom 38 patients underwent cardiac magnetic resonance imaging both at baseline and 12 weeks. There was no difference in recovery of LVEF between the experimental group (mean [SD] change, 4.0% [7.0%]) and the control group (mean [SD] change, 6.3% [6.3%]; mean difference, -2.4% [95% CI, -6.8% to 2.1%]; P = .29) or changes in left ventricular end-diastolic volume (mean difference, 13.4 [95% CI, -12.3 to 39.0] mL; P = .30) and end-systolic volume (mean difference, 11.4 [95% CI, -3.6 to 26.4] mL; P = .13). Late gadolinium enhancement as a percentage of the total left ventricular mass decreased to a larger extent in the experimental group (mean [SD], -13.6% [12.9%]) compared with the control group (mean [SD], -4.5% [9.5%]; mean difference, -9.1% [95% CI, -16.6% to -1.6%]; P = .02). Conclusions and Relevance: In this trial, treatment with paroxetine did not improve LVEF after myocardial infarction compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03274752.

Post-tonsillectomy hemorrhage rates in children compared by surgical technique.

Despite the sheer number of pediatric tonsillectomies performed in the United States annually, there is no clear consensus as to which surgical technique is superior. One way to compare surgical techniques is to study the morbidity associated with each. We report postoperative hemorrhage rates, one of the frequently encountered major adverse events, as part of a retrospective chart review across four different surgical techniques. These surgeries involved either (1) Coblation, (2) Co-blation with partial suture closure of the tonsillar fossa, (3) diathermy, or (4) partial intracapsular tonsillectomy (PIT). Of the 7,024 children we evaluated, 99 (1.4%) experienced a postoperative hemorrhage that required a second surgery; hemorrhage occurred after 33 of the 3,177 Coblation-alone procedures (1.04%), 28 of the 1,633 Coblation with partial suture closure procedures (1.71%), 29 of the 1,850 diathermies (1.57%), and 9 of the 364 PIT procedures (2.47%). Statistical analysis of hemorrhage rates with each surgical technique yielded p values >0.05 in each case (Coblation alone and Coblation with partial suture closure: p = 0.29; diathermy: p = 0.47; PIT, p = 0.20). Based on these data, we conclude that none of these techniques is significantly superior in terms of decreasing the risk of post-tonsillectomy hemorrhage in children. Therefore, surgeons should continue to use the surgical procedure they are most familiar with to optimize recovery in the postoperative period.

HPV Carcinomas in Immunocompromised Patients.

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient.

Zosteriform metastasis of rectal adenocarcinoma: a case report.

Cutaneous metastases manifesting as zosteriform eruptions are uncommon. To our knowledge, we report the second case of zosteriform cutaneous metastasis arising from a rectal carcinoma in a 58-year-old man who presented with a painless popular eruption in the T12 dermatomal distribution nine months after his primary diagnosis of rectal carcinoma was made. Furthermore, we discuss a review of the literature regarding zosteriform cutaneous metastases and the possible pathogenesis of these lesions.

Pediatric recurrent laryngeal nerve reinnervation: A case series and analysis of post-operative outcomes.

OBJECTIVE: To provide detailed information about recurrent laryngeal nerve (RLN) reinnervation outcomes in children using objective measures. METHODS: The records of three pediatric patients with unilateral vocal cord paralysis that underwent RLN reinnervation were retrospectively reviewed. Fundamental frequency (F0), jitter, shimmer, noise-to-harmonic ratio (NHR), and voice phonation (sustained /s/, /z/, /a/) were measured preoperatively and post-operatively at 13, 9, and 33 months (each time period corresponding to one of the three patients). RESULTS: Mean preoperative and post-operative variables were as follows: shimmer, 9.65±1.02% vs. 4.46±0.71% (p=0.01); NHR, 0.296±0.063 vs. 0.127±0.011 (p=0.04); jitter, 3.57±0.89% vs. 1.46±0.54% (p=0.08); F0, 274.6±35.4Hz vs. 282.2±70.6Hz (p=0.44); maximum phonation time, 7.46±1.40s vs. 9.79±1.84s (p=0.22); /s:z/ ratio, 1.28±0.22 vs.1.07±0.09 (p=0.26). CONCLUSIONS: There was statistically significant improvement in shimmer and NHR. Jitter improvement approached statistical significance. All other variables failed to show significant improvement among this small sample size. RLN reinnervation for pediatric patients is an option for the treatment of vocal cord paralysis. Further studies with larger cohorts are needed to show the full benefits.

Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer.

PURPOSE: Bisphosphonates have been shown to inhibit and deplete macrophages. The effects of bisphosphonates on other cell types in the tumor microenvironment have been insufficiently studied. Here, we sought to determine the effects of bisphosphonates on ovarian cancer angiogenesis and growth via their effect on the microenvironment, including macrophage, endothelial and tumor cell populations. EXPERIMENTAL DESIGN: Using in vitro and in vivo models, we examined the effects of clodronate on angiogenesis and macrophage density, and the overall effect of clodronate on tumor size and metastasis. RESULTS: Clodronate inhibited the secretion of pro-angiogenic cytokines by endothelial cells and macrophages, and decreased endothelial migration and capillary tube formation. In treated mice, clodronate significantly decreased tumor size, number of tumor nodules, number of tumor-associated macrophages and tumor capillary density. CONCLUSIONS: Clodronate is a potent inhibitor of tumor angiogenesis. These results highlight clodronate as a potential therapeutic for cancer.

Cutaneous metastasis of papillary thyroid carcinoma to the neck: a case report and review of the literature.

Papillary thyroid carcinoma, the most common subtype of thyroid malignancy, rarely presents with cutaneous metastatic spread. Despite metastatic cutaneous lesions presenting as slow and indolent growing nodules of the head and neck, such lesions most frequently appear in the setting of diffuse and dramatic metastatic disease and a bleak prognosis. Given the rarity of these metastatic lesions, the diagnosis may be delayed, and often the initial diagnosis is incorrect. Several case reports have been published in the literature noting unusual or interesting presentations of thyroid carcinoma with cutaneous metastasis. Here we present a classic case of a patient with a prior diagnosis of thyroid carcinoma presenting with a slowly growing ulcerated lesion on the neck nine years after partial thyroidectomy and characteristic histopathology on microscopic examination. Furthermore we review the literature regarding papillary thyroid carcinoma with cutaneous metastasis and the diagnostic challenge these lesions present to practitioners.

Chronic social stress impairs virus specific adaptive immunity during acute Theiler's virus infection.

Prior exposure to social disruption (SDR) stress exacerbates Theiler's murine encephalomyelitis virus (TMEV) infection, a model of multiple sclerosis. Here we examined the impact of SDR on T cell responses to TMEV infection in SJL mice. SDR impaired viral clearance and exacerbated acute disease. Moreover, TMEV infection alone increased CD4 and CD8 mRNA expression in brain and spleen while SDR impaired this response. SDR decreased both CD4(+) and CD8(+) virus-specific T cells in CNS, but not spleen. These findings suggest that SDR-induced suppression of virus-specific T cell responses contributes to impairments in viral clearance and exacerbation of acute disease.