Ragheb Assaly | The University of Toledo (original) (raw)

Papers by Ragheb Assaly

Journal of Medical Virology, Apr 3, 2021

T A B L E 2 Detailed data regarding positivity of viral culture and subgenomic RNA for each patie... more T A B L E 2 Detailed data regarding positivity of viral culture and subgenomic RNA for each patient in the included studies Patient number Study, year Choi, 2020 Positive (Days 75 and 143) NR Abbreviation: NR, not reported.

American Journal of Gastroenterology

Current Problems in Cardiology

Cureus

Background Coronavirus disease 2019 (COVID-19) infection can vary from asymptomatic infection to ... more 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 nonsurvivors. 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 nonsurvivors 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.

Intensive Care Medicine Experimental, 2016

Cureus

Background: Coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of... more Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Superior vena cava syndrome with retropharyngeal edema

Frontiers in Neurology, 2020

Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. ... more Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19. Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection. Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10 −12) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death. Salahuddin et al. Neurological Predictors in COVID-19 Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.

American Journal of Therapeutics, 2020

Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as semaglutide, are a promising and effe... more Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as semaglutide, are a promising and effective class of diabetes medication. GLP-1R agonists act by stimulating endogenous secretion of insulin from pancreatic beta cells and reducing production of glucagon from pancreatic alpha cells.1 The Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes (SUSTAIN-1) trial found the overall safety profile of semaglutide to be similar to currently available GLP-1R agonists, with the most frequently reported adverse effects being gastrointestinal in nature, either nausea or diarrhea.2 Diarrhea can be distressing for patients, especially chronic diarrhea lasting longer than 4 weeks.3 Although diarrhea has been identified as an adverse effect of semaglutide use, diarrhea is also a well-established complication of long-term diabetes mellitus, particularly poorly controlled insulindependent diabetes with evidence of peripheral and autonomic neuropathy.4 Determining the etiology of chronic diarrhea in a diabetic patient taking semaglutide may pose a recurrent challenge to clinicians and result in exhaustive and invasive diagnostic studies for the patient. We discuss the use of stool osmotic gap as a cost effective and noninvasive study that may be effective in determining the etiology of chronic diarrhea in diabetic patients taking GLP-1R agonists.

American Journal of Therapeutics, 2020

Fluoroquinolones (FQs) are commonly used antibiotics that exert their bactericidal effects by dir... more Fluoroquinolones (FQs) are commonly used antibiotics that exert their bactericidal effects by directly inhibiting bacterial DNA synthesis.1,2 Despite the efficacy of these agents, the potential for significant adverse events exists. The FDA issued the first black box warning in July 2008 for the increased risk of tendinitis and tendon rupture with use.3 These warnings have since been expanded and now include warnings for the risk of aortic ruptures or tears. This warning urges health care professionals to avoid the use of these agents in patients with an aortic aneurysm or in patients at high risk for an aortic aneurysm, including patients with Marfan syndrome and Ehlers–Danlos syndrome.4 Although the exact mechanism remains unknown, animal and cellular studies have provided information on the potential pathophysiology of FQ-induced collagen disruption, which likely involves the upregulation of metalloproteinase, leading to a reduction in the amount and quality of collagen.5,6 Other proposed mechanisms include direct collagen toxicity and changes in proteoglycan synthesis with concomitant oxidative damage.7,8 Structure–activity relationships have also been investigated, providing hypotheses that damage may be related to fluorinated quinolones or the presence of a methylpiperadinyl moiety at the seventh position of the drug molecule.9,10 However, additional studies are required to continue assessing the underlying mechanism and to determine whether a true structure–activity relationship is present.

Journal of Medical Virology, 2020

American Journal of Gastroenterology, 2014

Journal of the American College of Cardiology, 2019

Background: Tachy-Brady syndrome, a form of sick sinus syndrome occurs due to sinoatrial node dys... more Background: Tachy-Brady syndrome, a form of sick sinus syndrome occurs due to sinoatrial node dysfunction. Rarely, it can be mimicked by autonomic dysfunction. Case: A 54 year old female with history significant for triple negative metastatic breast cancer presented complaining of elevated BPs following a physical therapy session. Overnight telemetry noted sinus tachycardia & bradycardia (with HRs as low as 34) with a 3 second pause. TSH & T4 were within normal limits. The patient was not on beta-blockers or calcium channel blockers prior to presentation and had no previous cardiac history. ECHO revealed no primary valve disease. The patient was being evaluated for pacemaker implantation. She then began to complain of transient left leg weakness. MRI demonstrated subtle abnormal meningeal enhancement along the pons and distal cord raising concern for leptomeningeal carcinomatosis (LC). Lumbar puncture noted malignant cells within the CSF, confirming the diagnosis of LC. Decision-making: LC traditionally presents with clinical features of obstruction of normal CSF flow, such as headaches, cranial nerve deficits, and dizziness. Rarely (~1% of cases), it can present with autonomic dysfunction. Unfortunately the diagnosis carries a poor prognosis, and survival is typically 6-8 weeks without treatment, and 2-4 months with treatment. Conclusion: Though uncommon, autonomic dysfunction of LC can mimic ECG findings associated with sinus node dysfunction.

Journal of Clinical Medicine

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive ... more The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81–0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79–0.95), and AKI (RR 0.85, 95% CI 0.77–0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90–1.03), need for RRT (RR 0.91, 95% CI 0.76–1.08), an...

Cureus, Mar 31, 2022

Drug-induced nephrotoxicity and neurotoxicity are commonly encountered problems in clinical pract... more Drug-induced nephrotoxicity and neurotoxicity are commonly encountered problems in clinical practice. We describe a case of concurrent valacyclovir-induced nephrotoxicity and neurotoxicity in a 64-year-old man with no history of renal disease who developed acute renal injury and neurological symptoms after he received two weeks of the standard dose of oral valacyclovir for herpes zoster meningitis. His clinical condition improved significantly after the initiation of hemodialysis. Although nephrotoxicity due to intravenous infusion of valacyclovir and/or acyclovir is not uncommon, oral valacyclovir therapy is rarely associated with nephrotoxicity in patients with no history of renal insufficiency. Additionally, concurrent nephrotoxicity and neurotoxicity due to valacyclovir and/or acyclovir are rarely reported. Clinicians should be aware of these adverse events as immediate recognition and intervention are necessary to prevent morbidity.

American Journal of Therapeutics, 2022

Clinical Nutrition ESPEN, 2022

Background and aims Micronutrient supplements such as vitamin D, vitamin C, and zinc have been us... more Background and aims Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19. Methods We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. Results We identified 26 studies (10 randomized controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62-1.62, P=1.00), intubation rate (RR 1.77, 95% CI 0.56-5.56, P=0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P=0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49-1.17, P=0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32-0.97, P=0.04) and LOS (MD -1.26; 95% CI -2.27, -0.25; P=0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60-1.03, P=0.08). Conclusions Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.

Lupus, 2021

Legionnaire’s disease (LD) is most commonly caused by Legionella pneumophila (L. pneumophila). In... more Legionnaire’s disease (LD) is most commonly caused by Legionella pneumophila (L. pneumophila). In immunocompromised patients LD can cause necrosis of the lung parenchyma with abscess formation and cavitation. Systemic lupus erythematosus (SLE) is an autoimmune disorder with features of both primary and secondary immunodeficiency. SLE patients often develop pulmonary abnormalities, but rarely develop lung cavitations. We report a case of cavitary pneumonia caused by L. pneumophila in a 64-year-old female patient with SLE. We also highlight reasons why SLE patients are more prone to L. pneumophila infections. The importance of using correct diagnostic methods for recognizing and treating such infections is also discussed, as mistreatment of cavitary lesions in SLE patients with steroid therapy can have fatal outcomes as the infectious process can significantly worsen.

Journal of Medical Virology, Apr 3, 2021

T A B L E 2 Detailed data regarding positivity of viral culture and subgenomic RNA for each patie... more T A B L E 2 Detailed data regarding positivity of viral culture and subgenomic RNA for each patient in the included studies Patient number Study, year Choi, 2020 Positive (Days 75 and 143) NR Abbreviation: NR, not reported.

American Journal of Gastroenterology

Current Problems in Cardiology

Cureus

Background Coronavirus disease 2019 (COVID-19) infection can vary from asymptomatic infection to ... more 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 nonsurvivors. 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 nonsurvivors 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.

Intensive Care Medicine Experimental, 2016

Cureus

Background: Coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of... more Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Superior vena cava syndrome with retropharyngeal edema

Frontiers in Neurology, 2020

Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. ... more Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19. Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection. Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10 −12) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death. Salahuddin et al. Neurological Predictors in COVID-19 Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.

American Journal of Therapeutics, 2020

Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as semaglutide, are a promising and effe... more Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as semaglutide, are a promising and effective class of diabetes medication. GLP-1R agonists act by stimulating endogenous secretion of insulin from pancreatic beta cells and reducing production of glucagon from pancreatic alpha cells.1 The Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes (SUSTAIN-1) trial found the overall safety profile of semaglutide to be similar to currently available GLP-1R agonists, with the most frequently reported adverse effects being gastrointestinal in nature, either nausea or diarrhea.2 Diarrhea can be distressing for patients, especially chronic diarrhea lasting longer than 4 weeks.3 Although diarrhea has been identified as an adverse effect of semaglutide use, diarrhea is also a well-established complication of long-term diabetes mellitus, particularly poorly controlled insulindependent diabetes with evidence of peripheral and autonomic neuropathy.4 Determining the etiology of chronic diarrhea in a diabetic patient taking semaglutide may pose a recurrent challenge to clinicians and result in exhaustive and invasive diagnostic studies for the patient. We discuss the use of stool osmotic gap as a cost effective and noninvasive study that may be effective in determining the etiology of chronic diarrhea in diabetic patients taking GLP-1R agonists.

American Journal of Therapeutics, 2020

Fluoroquinolones (FQs) are commonly used antibiotics that exert their bactericidal effects by dir... more Fluoroquinolones (FQs) are commonly used antibiotics that exert their bactericidal effects by directly inhibiting bacterial DNA synthesis.1,2 Despite the efficacy of these agents, the potential for significant adverse events exists. The FDA issued the first black box warning in July 2008 for the increased risk of tendinitis and tendon rupture with use.3 These warnings have since been expanded and now include warnings for the risk of aortic ruptures or tears. This warning urges health care professionals to avoid the use of these agents in patients with an aortic aneurysm or in patients at high risk for an aortic aneurysm, including patients with Marfan syndrome and Ehlers–Danlos syndrome.4 Although the exact mechanism remains unknown, animal and cellular studies have provided information on the potential pathophysiology of FQ-induced collagen disruption, which likely involves the upregulation of metalloproteinase, leading to a reduction in the amount and quality of collagen.5,6 Other proposed mechanisms include direct collagen toxicity and changes in proteoglycan synthesis with concomitant oxidative damage.7,8 Structure–activity relationships have also been investigated, providing hypotheses that damage may be related to fluorinated quinolones or the presence of a methylpiperadinyl moiety at the seventh position of the drug molecule.9,10 However, additional studies are required to continue assessing the underlying mechanism and to determine whether a true structure–activity relationship is present.

Journal of Medical Virology, 2020

American Journal of Gastroenterology, 2014

Journal of the American College of Cardiology, 2019

Background: Tachy-Brady syndrome, a form of sick sinus syndrome occurs due to sinoatrial node dys... more Background: Tachy-Brady syndrome, a form of sick sinus syndrome occurs due to sinoatrial node dysfunction. Rarely, it can be mimicked by autonomic dysfunction. Case: A 54 year old female with history significant for triple negative metastatic breast cancer presented complaining of elevated BPs following a physical therapy session. Overnight telemetry noted sinus tachycardia & bradycardia (with HRs as low as 34) with a 3 second pause. TSH & T4 were within normal limits. The patient was not on beta-blockers or calcium channel blockers prior to presentation and had no previous cardiac history. ECHO revealed no primary valve disease. The patient was being evaluated for pacemaker implantation. She then began to complain of transient left leg weakness. MRI demonstrated subtle abnormal meningeal enhancement along the pons and distal cord raising concern for leptomeningeal carcinomatosis (LC). Lumbar puncture noted malignant cells within the CSF, confirming the diagnosis of LC. Decision-making: LC traditionally presents with clinical features of obstruction of normal CSF flow, such as headaches, cranial nerve deficits, and dizziness. Rarely (~1% of cases), it can present with autonomic dysfunction. Unfortunately the diagnosis carries a poor prognosis, and survival is typically 6-8 weeks without treatment, and 2-4 months with treatment. Conclusion: Though uncommon, autonomic dysfunction of LC can mimic ECG findings associated with sinus node dysfunction.

Journal of Clinical Medicine

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive ... more The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81–0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79–0.95), and AKI (RR 0.85, 95% CI 0.77–0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90–1.03), need for RRT (RR 0.91, 95% CI 0.76–1.08), an...

Cureus, Mar 31, 2022

Drug-induced nephrotoxicity and neurotoxicity are commonly encountered problems in clinical pract... more Drug-induced nephrotoxicity and neurotoxicity are commonly encountered problems in clinical practice. We describe a case of concurrent valacyclovir-induced nephrotoxicity and neurotoxicity in a 64-year-old man with no history of renal disease who developed acute renal injury and neurological symptoms after he received two weeks of the standard dose of oral valacyclovir for herpes zoster meningitis. His clinical condition improved significantly after the initiation of hemodialysis. Although nephrotoxicity due to intravenous infusion of valacyclovir and/or acyclovir is not uncommon, oral valacyclovir therapy is rarely associated with nephrotoxicity in patients with no history of renal insufficiency. Additionally, concurrent nephrotoxicity and neurotoxicity due to valacyclovir and/or acyclovir are rarely reported. Clinicians should be aware of these adverse events as immediate recognition and intervention are necessary to prevent morbidity.

American Journal of Therapeutics, 2022

Clinical Nutrition ESPEN, 2022

Background and aims Micronutrient supplements such as vitamin D, vitamin C, and zinc have been us... more Background and aims Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19. Methods We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. Results We identified 26 studies (10 randomized controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62-1.62, P=1.00), intubation rate (RR 1.77, 95% CI 0.56-5.56, P=0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P=0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49-1.17, P=0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32-0.97, P=0.04) and LOS (MD -1.26; 95% CI -2.27, -0.25; P=0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60-1.03, P=0.08). Conclusions Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.

Lupus, 2021

Legionnaire’s disease (LD) is most commonly caused by Legionella pneumophila (L. pneumophila). In... more Legionnaire’s disease (LD) is most commonly caused by Legionella pneumophila (L. pneumophila). In immunocompromised patients LD can cause necrosis of the lung parenchyma with abscess formation and cavitation. Systemic lupus erythematosus (SLE) is an autoimmune disorder with features of both primary and secondary immunodeficiency. SLE patients often develop pulmonary abnormalities, but rarely develop lung cavitations. We report a case of cavitary pneumonia caused by L. pneumophila in a 64-year-old female patient with SLE. We also highlight reasons why SLE patients are more prone to L. pneumophila infections. The importance of using correct diagnostic methods for recognizing and treating such infections is also discussed, as mistreatment of cavitary lesions in SLE patients with steroid therapy can have fatal outcomes as the infectious process can significantly worsen.