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Introduction: Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO2), reduce fraction of inspired oxygen (FiO2) requirements, and ultimately increase PaO2/FiO2 (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Methods: Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). Results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Conclusion: Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.

Recent clinical trials have investigated the use of fluvoxamine in preventing clinical deterioration in nonhospitalized patients with acute COVID-19 infection via stimulation of sigma-1 receptors, which regulates cytokine production and functional inhibition of acid sphingomyelinase activity, which may prevent infection of epithelial cells with SARS-CoV-2. However, the role of fluvoxamine is currently unclear because of a paucity of studies, particularly because the drug is being repurposed as an immunomodulatory and antiviral agent.Aim of our meta-analysis was to investigate the efficacy of fluvoxamine in nonhospitalized patients with acute COVID-19 infection.Comprehensive literature search of PubMed, Embase, Cochrane Library databases, and Web of Science was performed from inception to February 10, 2022, for studies comparing fluvoxamine versus placebo for outpatient management of COVID-19.The primary outcome of interest was rate of hospitalization. The secondary outcomes were rates of patients requiring mechanical ventilation and mortality. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A P value0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index.Three studies (2 randomized controlled trials and one prospective cohort trial) involving 1762 patients were included in the meta-analysis. In patients who received fluvoxamine compared with placebo, there was no significant difference in rates of hospitalization (RR 0.26, 95% CI, 0.04-1.73, P = 0.16, I2 = 62%), mechanical ventilation (RR 0.73, 95% CI, 0.45-1.19, P = 0.21, I2 = 0%), and mortality (RR 0.67, 95% CI, 0.37-1.22, P = 0.19, I2 = 0%).Current evidence does not indicate a significant effect of fluvoxamine on the rates of hospitalization, mechanical ventilation, and mortality of patients with COVID-19 infection.

Background Coronavirus disease 2019 (COVID-19) infection can vary from asymptomatic infection to multi-organ dysfunction. The most serious complication of infection with COVID-19 is death. Various comorbid conditions and inflammatory markers have been associated with an increased risk of mortality, specifically within the immediate post-infection period; however, less is known about long-term mortality outcomes. Objectives Our objective is to determine risk factors associated with six-month mortality in hospitalized COVID-19 patients. Methods This is a single-institution, retrospective study. We included patients hospitalized with COVID-19 from the University of Toledo Medical Center in Toledo, Ohio, who were admitted from March 20, 2020, to June 30, 2021. This study was approved by a biomedical institutional review board at the University of Toledo. Patients with available pre-stored blood samples for laboratory testing were included, and hospital charts were assessed up to six months from the date of a positive COVID-19 test result. Two groups were created based on the mortality outcome at six months from COVID-19 positive test results: survivors and non-survivors. The clinical variables or outcomes and laboratory values were compared between the two groups using non-parametric methods due to the small sample size and non-normality of the data. Either the Mann-Whitney U-test for continuous variables or Fisher's exact test for categorical variables was used for statistical analysis. Results Lactate dehydrogenase (LDH) and D-dimer levels on admission were found to be significantly higher in non-survivors than in survivors. The median high D-dimer level in non-survivors was 5.96 micrograms/milliliter (μg/mL) (interquartile range (IQR): 3.95-11.29 μg/mL) vs 1.82 μg/mL (IQR 1.13-5.55 μg/mL) in survivors (p = 0.019). Median LDH levels were also higher in non-survivors vs survivors, i.e., 621.00 international units per liter (IU/L) (IQR 440.00-849.00 IU/L) vs 328.00 IU/L (IQR 274.00-529.00 IU/L), respectively (p = 0.032). The demographic profile, comorbidity profile, and laboratory data (typically associated with short-term mortality, inflammation, and organ dysfunction) were similar between survivors and non-survivors, except for LDH and D-dimer. Conclusion Higher LDH and D-dimer levels on admission were found to be associated with an increased six-month mortality rate in hospitalized COVID-19 patients. These hematologic data can serve as risk stratification tools to prevent long-term mortality outcomes and provide proactive clinical care in hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of arterial thromboembolic events (ATE) and venous thromboembolic events (VTE). Hypercoagulability associated with COVID-19 infection is multifactorial, and underlying pathogenic mechanisms potentially responsible for thrombosis include inflammation resulting in endothelial damage, platelet activation and the presence of antiphospholipid antibodies (APAs). Antiphospholipid antibody syndrome is one of the very few causes which is associated with venous and arterial thromboembolic events. COVID-19 patients have a high prevalence of APAs as well as both ATE and VTE, but their clinical significance in COVID-19 patients is not fully understood yet.In this study, we intend to find the prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis and determine whether their presence has any clinical significance.This is a retrospective single-institution study involving patients hospitalized for the management of COVID-19 infection at The University of Toledo Medical Center. After obtaining approval from the biomedical institutional review board at The University of Toledo, antiphospholipid antibody (APA) testing was done on pre-stored blood samples of these patients and hospital charts were reviewed till six months from the positive COVID-19 test result. Two groups were created based on the patients' APA testing results (APA positive and APA negative) and used for statistical comparison. Any patients with positive lupus anticoagulant (LA) or abnormal titers APA antibodies were labeled as positive. Demographic data, prognostic outcomes and laboratory values were compared either using Mann-Whitney U-test for continuous variables or Fisher's exact test for categorical variables.The prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis was 39.3% in this study. There was no difference in demographic variables between the APA-positive and APA-negative groups. The prevalence of APAs was higher in smokers, where 91% of the APA-positive patients were smokers. There was no statistically significant difference in prognostic outcomes including six-month mortality between APA-positive and APA-negative patients. The comorbidity profile was the same in the two groups. APA-positive patients were found to have lower nadir of absolute lymphocyte count and higher nadir levels of C-reactive protein during hospitalization.The prevalence of APA positivity in hospitalized COVID-19 patients is higher in our study than in historical studies involving non-COVID-19 hospitalized patients, particularly in smokers. However, there is no correlation between APA positivity and prognostic outcomes including six-month mortality. At this point, it is unclear whether APAs are just bystanders or have a pathogenic role. Routine testing of APA in COVID-19 patients is not indicated. Further prospective studies to elucidate the persistence and clinical implications of APAs are needed.

Background: Given the potential for type 2 diabetes and the protective benefits of breastfeeding after gestational diabetes mellitus (GDM), there is a need to promote and support breastfeeding; however, delayed lactogenesis and postpartum experiences may challenge breastfeeding success. We aimed to describe factors that influence breastfeeding duration and satisfaction after GDM.Methods: A cross-sectional survey, informed by an elicitation phase and subject matter expert review, was conducted to evaluate factors associated with breastfeeding satisfaction and duration after GDM. The study included women (n = 50) from Northwest Ohio who delivered a living child from a singleton pregnancy at greater than or equal to 34 weeks gestation, who intended to breastfeed after GDM. Spearman correlation and Mann-Whitney U test were calculated to evaluate factors associated with breastfeeding duration and satisfaction.Results: Women described a lack of breastfeeding support, and there appeared to be a lack of awareness on the benefits of breastfeeding after GDM. Attitudes were associated with breastfeeding duration and satisfaction. Negative experiences in the child’s first week of life were associated with shorter duration and lower level of satisfaction. Delayed lactogenesis, barriers after delivery, and negative normative influences were significantly associated with a lower level of breastfeeding satisfaction.Conclusion: More work is needed to deliver breastfeeding education and support after GDM. Interventions tailored for GDM are recommended to promote positive breastfeeding beliefs and realistic breastfeeding expectations. Ongoing support to address early experiences and barriers after GDM is recommended. Further work should examine these factors in a larger, more diverse sample.

Systemic steroids are associated with reduced mortality in hypoxic patients with coronavirus disease 2019 (COVID-19). However, there is no consensus on the doses of steroid therapy in these patients. Several studies showed that pulse dose steroids (PDS) could reduce the progression of COVID-19 pneumonia. However, data regarding the role of PDS in COVID-19 is still unclear. Therefore, we performed this meta-analysis to evaluate the role of PDS in COVID-19 patients compared to nonpulse steroids (NPDS). Comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception through February 10, 2022 was performed for all published studies comparing PDS to NPDS therapy to manage hypoxic patients with COVID-19. Primary outcome was mortality. Secondary outcomes were the need for endotracheal intubation, hospital length of stay (LOS), and adverse events in the form of superimposed infections. A total of 10 observational studies involving 3065 patients (1289 patients received PDS and 1776 received NPDS) were included. The mortality rate was similar between PDS and NPDS groups (risk ratio [RR]: 1.23, 95% confidence interval [CI]: 0.92-1.65, p = 0.16). There were no differences in the need for endotracheal intubation (RR: 0.71, 95%: CI 0.37-1.137, p = 0.31), LOS (mean difference: 1.93 days; 95% CI: -1.46-5.33; p = 0.26), or adverse events (RR: 0.93, 95% CI: 0.56-1.57, p = 0.80) between the two groups. Compared to NPDS, PDS was associated with similar mortality rates, need for endotracheal intubation, LOS, and adverse events. Given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings.

In the COVID-19 pandemic, to minimize aerosol-generating procedures, cardiac magnetic resonance imaging (CMR) was utilized at our institution as an alternative to transesophageal echocardiography (TEE) for diagnosing infective endocarditis (IE). This retrospective study evaluated the clinical utility of CMR for detecting IE among 14 patients growing typical microorganisms on blood cultures or meeting modified Duke Criteria. Seven cases were treated for IE. In 2 cases, CMR results were notable for possible leaflet vegetations and were clinically meaningful in guiding antibiotic therapy, obtaining further imaging, and/or pursuing surgical intervention. In 2 cases, vegetations were missed on CMR but detected on TEE. In 3 cases, CMR was non-diagnostic, but patients were treated empirically. There was no difference in antibiotic duration or outcomes over 1 year. CMR demonstrated mixed results in diagnosing valvular vegetations and guiding clinical decision-making. Further prospective controlled trials of CMR Vs TEE are warranted.

ImportanceMelanoma accounts for most of the deaths due to skin cancer. In the past decade, effective US Food and Drug Administration (FDA)–approved therapies for melanoma have emerged.ObjectiveTo review changes in the long-term melanoma mortality rate (MMR) trends in the US and determine whether they have any temporal association with the FDA approval of new agents.Design, Setting, and ParticipantsThis cross-sectional study used population data from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed the age-adjusted MMR trends in adult patients (aged ≥18 years) from 1975 to 2019 in the US population. The timeline of the FDA approvals for melanoma treatment was also reviewed. Data were analyzed from March 15 to August 15, 2022.ExposuresOutcomes were assessed in association with FDA approval of drugs for the treatment of melanoma.Main Outcomes and MeasuresMortality rates are from the SEER database, reported per 100 000 population and age-adjusted to the 2000 US standard population. The annual percent change (APC) has been used to report long-term trends.ResultsAfter the introduction of newer treatments in 2011 (most after 2013), a significant reduction in MMR was seen from 2013 to 2017 in the US for the first time in the past 40 years. Rates increased from 1975 to 1988 (APC, 1.65% [95% CI, 1.30%-2.00%]; P P = .85). The MMR decreased significantly from 2013 to 2017 (APC, −6.28% [95% CI, −8.52% to −3.97%]; P Conclusions and RelevanceThese findings suggest a benefit associated with the availability of effective therapies in the past decade and further suggest that the use of new pharmacological therapies is associated with decreased MMR in the US population. These data are very encouraging and support the continued development of such therapies. Additionally, the accessibility of these treatments and the associated health care costs need to be addressed.

Insulin resistance (IR), which can be assessed by triglyceride-glucose (TyG) index, is a major contributor to the pathogenesis of cardiovascular diseases. Arterial stiffness is an index of subclinical atherosclerosis. We conducted this systematic review and meta-analysis to summarize the existing studies and provide a quantitative assessment of the significance of the TyG index in predicting the incidence of subclinical atherosclerosis and arterial stiffness. A comprehensive literature search in PubMed, EMBASE, and Web of Science databases from inception until April 30, 2022 was conducted. Published observational studies that evaluated the association between TyG index and arterial stiffness among the adult population and reported odds ratio (OR) for this association after multivariate analysis were included. The random-effects model was used for the estimation of pooled ORs with the corresponding confidence intervals (CIs). A total of 9 observational studies, including 37780 participants, were included. Seven out of the 9 studies analyzed the TyG index as a categorical variable and showed a statistically significant association between TyG index and incident arterial stiffness (pooled OR 1.96, 95% CI 1.52-2.53, P0.00001, I

Background Left ventricular thrombus (LVT) may develop in systolic heart failure or after acute myocardial infarction. The current recommendations support the use of vitamin K antagonists (VKAs) for the treatment of LVT. Limited data exist regarding the use of direct oral anticoagulants (DOACs) in patients with LVT. This meta-analysis aims to investigate the efficacy and safety of DOACs versus VKAs for LVT. Methods We performed a comprehensive literature search using PubMed, Embase, and Cochrane Library databases through November 2020 for all studies that evaluated the efficacy and safety of DOACs versus VKAs in patients with LVT. The primary outcomes were LVT resolution, overall thromboembolic events, and thromboembolic stroke. The secondary outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effects model. Heterogeneity was assessed by I2 statistic. Results A total of 11 studies including 2153 patients with LVT on anticoagulation (570 on DOACs vs. 1583 on VKAs) were included. LVT resolution was significantly higher in DOACs compared with VKAs [RR: 1.18 (95% CI: 1.04-1.35); P = 0.01, I2 = 25%]. However, no significant difference existed between DOACs and VKAs regarding overall thromboembolic events [RR: 1.10 (95% CI: 0.75-1.62); P = 0.61, I2 = 0%] and thromboembolic stroke [RR: 0.63 (95% CI: 0.39-1.02); P = 0.06, I2 = 0%]. Major bleeding [RR: 1.00 (95% CI: 0.66-1.51); P = 0.99, I2 = 4%] and all-cause mortality [RR: 0.84 (95% CI: 0.50-1.43); P = 0.53, I2 = 0%] were similar between the 2 groups. Conclusions DOACs seem to be more efficacious in achieving LVT resolution compared with VKAs. However, there was no significant difference between the 2 groups in thromboembolic events, major bleeding, and all-cause mortality. Randomized controlled trials are needed to confirm our findings.

Henoch-Schonlein purpura (HSP) is a multi-system autoimmune disease that is relatively common in pediatric patients. HSP usually manifests as palpable purpura, arthralgia, abdominal pain, and acute kidney injury. Here, we present a case of an adult male with hematemesis as the initial presenting symptom of HSP. A previously healthy, 18-year-old Caucasian male presented with a one-day history of hematemesis associated with abdominal pain and non-bloody diarrhea. He also reported bilateral knee and ankle arthralgias with a painless skin rash on both lower extremities. Physical exam was positive for palpable, purpuric, non-blanchable skin rash involving bilateral lower extremities. Notable labs on admission included a white cell count of 10.8 x 109/L and C-reactive protein of 4.8 mg/L. Upper endoscopy showed non-bleeding erosive gastropathy and duodenal erosions. Skin biopsy of the left leg showed immunoglobulin A (IgA) deposition within the walls of the superficial dermal vessels. The patient was started on intravenous methylprednisolone 500 mg daily followed by a steroid taper. Due to incomplete clinical response to steroids, mycophenolate mofetil 1000 mg twice daily was added and maintained for three months. His symptoms improved significantly, and he no longer complained of abdominal pain or diarrhea. Gastrointestinal manifestations are common in HSP patients. However, the diagnosis will be challenging when these symptoms precede other classical manifestations of HSP. History and physical exam are key components in accurately diagnosing HSP; nevertheless, skin biopsy remains the gold standard to confirm the diagnosis.

Pancreatic calculi are typically a sequela of chronic pancreatitis. Here, we present a patient who was found to have an obstructing one-centimeter pancreatic calculus secondary to recurrent gallstone pancreatitis. Recent retrospective studies have focused on the optimal treatment of large pancreatic calculi that were defined as greater than five millimeters. But most studies fail to comment on much larger stone as in this case report. Further guidelines and investigation need to be done aiming toward the optimal treatment of relatively large pancreatic stones.

Introduction: Amiodarone is an effective antiarrhythmic, but it is associated with altering thyroid function, ranging from thyrotoxicosis to hypothyroidism. In this study, we discuss amiodarone-induced hypothyroidism (AIH) presenting with hyponatremia and myxedema. Case Presentation: A 75-year-old Caucasian man with a history of ischemic heart disease with an ejection fraction of 55-60% was seen in the ED with complaints of worsening lower limb edema and shortness of breath. Associated symptoms of constipation, generalized weakness, daytime sleepiness, and increased urinary frequency were noted. He was recently diagnosed with atrial fibrillation with a CHA₂DS₂-Vasc score of 5 and started on amiodarone nine months ago. He weighed 235 lbs with a BMI of 33.85 and vital signs are as follows: blood pressure 90/64, heart rate 64, respiration rate 13, and a temperature of 36.6 °C. Physical examination revealed a well-developed man in mild distress and slightly lethargic, with a palpable thyroid gland, heart sounds revealed an irregularly irregular heart rate, elevated JVD, bilateral rales, and bilateral pitting edema. Labs showed mildly low HB of 11.7, low Na of 125 mmol/L, elevated creatinine at 1.67 mg/dl, low urine osmolality at 270 mOsm/kg, and BNP of 24 with negative troponin. Chest x-ray showed cardiomegaly. TSH was elevated at 93 uIU/mL and low free T4 at less than 0.25 ng/dL with a negative anti-TPO. A diagnosis of amiodarone-induced hypothyroidism was made, and the patient was started on increased furosemide and levothyroxine 25 mcg daily. Significant improvement was noted in mental status, sodium level, and volume status within three days; and the patient was discharged home on 50mcg of levothyroxine. Discussion: This case illustrates the need to constantly investigate the etiology of decompensated heart failure, especially when new medications with potential culprit side effects are noted or suspected. Amiodarone which is helpful in the management of atrial fibrillation has been known to cause thyroid dysfunction as hypo or hyperthyroidism. What is not widely known is that these endocrine dysfunctions can occur just a few weeks after therapy initiation. Conclusion: We recommend that patients who started on amiodarone be monitored for thyroid dysfunction; especially when they present with deterioration in the cardiac function or show symptoms of endocrinopathy.

It is recommended to attempt vagal maneuvers as initial therapy in various types of supraventricular tachycardia. While various forms of vagal techniques have been described, a gag reflex-mediated vagal technique, to the best of our knowledge, has not been. We present a case of gag reflex-mediated restoration of sinus rhythm in a patient with atrial fibrillation and rapid ventricular response upon transesophageal probe insertion. This case is unique due to the mechanism of vagally mediated cardioversion. It emphasizes that operators must be cautious regarding the risk of embolization of a potential thrombus from vagal-mediated cardioversion with unknown thrombus burden.

Introduction: Autoimmune polyglandular syndrome (APS) is a multiorgan genetic autoimmune disease. APS-3B subtype is autoimmune thyroiditis with pernicious anemia. In this case, we will discuss an elderly female patient diagnosed with APS-3B. Case Presentation: A 69-year-old Caucasian female patient with a past medical history of autoimmune thyroiditis presented to the emergency department with a two-month history of generalized weakness and nausea. Associated symptoms included shortness of breath and diarrhea. Review of systems was otherwise unremarkable. Physical exam was positive for depigmented skin macules over the upper extremities. Lab results showed hemoglobin 8.2 [11.7 - 15.5 g/dL], MCV 121[80 - 100 fL], platelets 144,000 [150 - 450 X10E9/L], WBC 1.9 [4.0 - 11.0 X10E9/L], LDH 1153[100 - 235 U/L], TSH 0.28[0.49 - 4.67 uIU/mL], free T4 1.7 [0.61 - 1.60 ng/dL], direct Coombs test negative. Iron saturation 55%, vitamin B12 level 25[>5.8 ng/mL], total bilirubin 2.3 [0.3 - 1.2 mg/dL], haptoglobin Discussion: The patient was diagnosed with autoimmune thyroiditis in 2014 with positive anti-TPO antibodies and elevated TSH; she required levothyroxine supplementation since diagnosis. Hypothyroidism causes macrocytic anemia, which may delay pernicious anemia diagnosis. APS-3B is associated with HLA-B8 and/or DR3 and DR5. Many studies reported that autoantibodies can be detected before developing symptoms of organ involvement. Thorough family history provides support for autoantibody testing to detect cases of APS-3B earlier. Active surveillance and early diagnosis will help minimize invasive testing such as bone marrow biopsy, so proper history taking is a key factor to early diagnose these conditions. Conclusion: APS-3B is a rare disorder. Diagnosis is difficult hypothyroidism causes macrocytic anemia. Early detection of APS-3B may help to prevent complications that increase the risk of mortality and morbidity, particularly in the elderly population.

Introduction: The annual incidence of hypopituitarism 4.2 cases of 100,000. Causes include primary tumor, metastasis, and non-tumor causes such as radiation therapy, infiltrative lesions, infection, and traumatic brain injury. Metastatic pituitary tumors constitute about 7-9% of the cases, with lung and breast cancers are the most common primary tumors. Case Presentation: 48-year-old Caucasian female patient with 30 pack-year smoking history presented to the emergency department with abdominal pain, diarrhea, fatigue, and headache. Review of systems was significant for loss of appetite, left eye visual field defect, anorexia, cold intolerance, and shortness of breath. Physical examination was remarkable for decreased visual acuity. Vital signs notable for hypotension BP 92/63. Notable labs include glucose of 53 mg/dL, TSH 0.50 [0.49 - 4.67 uIU/mL], low free T4 0.52 ng/dL, low FSH 1.3 mIU/ml, low LH Discussion: Patient’s 2011 MRI brain showed a mildly enlarged pituitary gland. MRI brain two months before admission showed a pituitary gland diameter of 1.6 cm, while an MRI at presentation showed a pituitary gland size of 2.4 cm with a new cerebellar lesion. She reported symptoms of nausea, vomiting, and weakness for more than one year ago but biochemical testing was not performed. The fact that the patient had pituitary enlargement eight years ago likely delayed the diagnosis of pituitary metastasis. Patient age precluded lung cancer screening despite smoking history and family history of lung cancer. Conclusion: Symptomatic patients with pituitary enlargement on brain imaging may benefit from a close follow-up and biochemical testing for early diagnosis and treatment, especially if they have risk factors for malignancy.