Beyond the myocardium? SGLT2 inhibitors target peripheral components of reduced oxygen flux in the diabetic patient with heart failure with preserved ejection fraction.

Recent cardiovascular outcome trials have highlighted the propensity of the antidiabetic agents, SGLT2 inhibitors (SGLT2is or -flozin drugs), to exert positive clinical outcomes in patients with cardiovascular disease at risk for major adverse cardiovascular events (MACEs). Of interest in cardiac diabetology is the physiological status of the patient with T2DM and heart failure with preserved ejection fraction (HFpEF), a well-examined association. Underlying this pathologic tandem are the effects that long-standing hyperglycemia has on the ability of the HFpEF heart to adequately deliver oxygen. It is believed that shortcomings in oxygen diffusion or utilization and the resulting hypoxia thereafter may play a role in underlying the clinical sequelae of patients with T2DM and HFpEF, with implications in the long-term decline of extra-cardiac tissue. Oxygen consumption is one of the most critical factors in indexing heart failure disease burden, warranting a probe into the role of SGLT2i on oxygen utility in HFpEF and T2DM. We investigated the role of oxygen flux in the patient with T2DM and HFpEF extending beyond the heart with focuses on cellular metabolism, perivascular fibrosis with endothelial dysfunction, hematologic changes, and renal effects with neurohormonal considerations in the patient with HFpEF and T2DM. Moreover, we give a commentary on potential therapeutic targets of these components with SGLT2i to gain insight into disease burden amelioration in patients with HFpEF and T2DM.

Acute inflammatory presentation of orbital metastasis from urothelial carcinoma: a case report.

Orbital metastasis of urothelial carcinoma is very rare; only 22 cases have been documented. In this case report, we describe a patient 1 month status post transurethral resection of urothelial carcinoma who presented with a clinical picture suggestive of orbital cellulitis. However, neither broad-spectrum antibiotics nor a subsequent trial of methylprednisolone was effective at relieving the patient's symptoms. CT imaging of the head, chest, abdomen, pelvis, and lower extremity showed no signs of metastatic disease. Six days after presentation, punch biopsy of the mass was performed and confirmed urothelial carcinoma metastatic to the orbit. The patient died 3 months later due to multiple sites of distant metastasis. This case report suggests that a high index of suspicion for orbital metastasis is important for patients with a history of urothelial carcinoma with new and acute onset of ocular symptoms and emphasizes the need for urgent systemic evaluation and treatment.

Neural tone and cardio-renal outcomes in patients with type 2 diabetes mellitus: a review of the literature with a focus on SGLT2 inhibitors.

Recent clinical trials involving the systemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have revealed beneficial outcomes pertaining to the microvascular sequelae of type 2 diabetes mellitus (T2DM) such as nephropathy, as well as macrovascular effects such as major adverse cardiovascular effects (MACE). Such findings have spurred the elevation of these agents to level A-tiers of recommendation within clinical guidelines addressing the management of complicated T2DM. While the mechanisms of SGLTi (-flozin drugs) are still being elucidated, a paucity of data exists within the literature appraising the role of neuromodulation and associated mechanisms in the aforementioned outcome studies. Given the role of the nervous system in orchestrating the pathologic processes that hamper cardio-renal status, insight into this topic offers an expanded perspective on T2DM. In this review we investigate the mechanisms by which SGLTi improve cardio-renal function in T2DM patients with emphases on neural tone and nervous system physiology.

Cases and etiologies of suspected COVID-19 reactivation.

Our article outlines a perspective on COVID-19 reactivation with considerations of implored commentary on behalf of the medical community regarding open discourse about this subject. Such a topic is paramount in elucidating parameters that pertain to testing, and subsequent public health population dynamics once uneventful cases pass. We argue that what some may refer to as a reinfection or reactivation of the virus, is actually a result of prolonged shedding of the virus complemented with occasional false positives/negatives and lab errors. This article was written with the perspective of informing in addition to engage discussions that distill salient, evidence-based characterization of COVID-19. We hope to recruit fellow academics in medicine who see trends in their own respective communities about people who re-test, and to explore their clinical outcomes.

More than meets the eye: rhino-orbital cerebral mucormycosis with diabetic ketoacidosis presenting as periorbital edema resulting in orbital exenteration and maxillectomy.

Mucormycosis is an invasive fungal infection that can cause acute clinical decompensation and death. The literature demonstrates case fatality rates around 50% with differential clinical courses contingent upon anatomical incursion. Rhino-orbital cerebral mucormycosis represents a rapidly hostile variant with poorer outcomes, warranting prompt recognition, workup, and intervention. It is seldom included in differential diagnoses in those with head and neck pathology within the inpatient setting as diagnostic parsimony and low prevalence lead this entity to be often overlooked. Given the acuity and risk factors involved, considering mucormycosis may be prudent during the assessment of hyperglycemic or immunodeficient patients exhibiting maxillofacial disease. When acquiring histories of presenting illness and performing physical examinations, assessment includes mindfulness of diabetes mellitus, craniofacial lesions, and alertness to clinical deterioration. Given the rising incidence of complicated diabetes mellitus in conjunction with a paucity of mucormycosis reports noting the orbit as the diagnostic harbinger, we report the case of a 59-year-old woman admitted to the critical care setting for diabetic ketoacidosis and altered mental status. Physical examination revealed a swollen orbit, later diagnosed as mucormycosis with associated sino-orbit involvement and cranial nerve deficits warranting urgent and extensive facial debridement.

Pharmacotherapy of refractory pulmonary arterial hypertension.

INTRODUCTION: Treatment of refractory pulmonary arterial hypertension (PAH) is challenging and rarely the focus of reviews. The purpose of this review is to discuss current treatment options of refractory PAH, along with the state of research of several new medications. AREAS COVERED: We conducted a comprehensive PubMed search on the relevant literature on treating PAH, with a focus on approved and investigational interventions for high-risk patients. Our strategy used keywords 'Treatment' AND 'Pulmonary Hypertension,' without date restrictions, ensuring a thorough survey of available literature for our review. EXPERT OPINION: By utilizing serial risk assessment to identify patients remaining intermediate or high-risk, more patients are likely to survive longer. This is done by earlier use of combination or triple therapy with prostacyclin drugs. Current medications for PAH are all essentially vasodilators that improve physiology, but do not truly modify the disease process. The potential application of new investigational medications is exciting as they work by novel pathways likely to change the landscape of refractory PAH treatment.

Acute Retinal Necrosis in an Immunocompetent Patient Treated With Intravitreal Ganciclovir.

Acute retinal necrosis (ARN) is an inflammatory syndrome of high clinical concern; untreated or misdiagnosed cases may progress to optic neuropathy or retinal detachment, leading to irreversible blindness. ARN affects men and women equally and is often seen in immunocompromised patients but is also known to present in immunocompetent patients. It is usually due to systemic viral infection with secondary vitreoretinal inflammation. Most commonly, the first-line management of ARN is oral or intravenous antiviral therapy. Here, we report the case of an immunocompetent patient presenting with necrotizing retinopathy secondary to ARN. This patient was treated with oral valacyclovir and then intravenous acyclovir with no improvement. However, intravitreal injection of ganciclovir successfully halted the progression of ARN and led to the preservation of vision in the patient.

Correction to: A Rare Presentation of Omental Lymphangioma Masquerading as Malignancy in an Adult Patient.

[This corrects the article on p. e00491 in vol. 7, PMID: 33324710.].

Cardiovascular benefits from SGLT2 inhibition in type 2 diabetes mellitus patients is not impaired with phosphate flux related to pharmacotherapy.

The beneficial cardiorenal outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) have been substantiated by multiple clinical trials, resulting in increased interest in the multifarious pathways by which their mechanisms act. The principal effect of SGLT2i (-flozin drugs) can be appreciated in their ability to block the SGLT2 protein within the kidneys, inhibiting glucose reabsorption, and causing an associated osmotic diuresis. This ameliorates plasma glucose elevations and the negative cardiorenal sequelae associated with the latter. These include aberrant mitochondrial metabolism and oxidative stress burden, endothelial cell dysfunction, pernicious neurohormonal activation, and the development of inimical hemodynamics. Positive outcomes within these domains have been validated with SGLT2i administration. However, by modulating the sodium-glucose cotransporter in the proximal tubule (PT), SGLT2i consequently promotes sodium-phosphate cotransporter activity with phosphate retention. Phosphatemia, even at physiologic levels, poses a risk in cardiovascular disease burden, more so in patients with type 2 diabetes mellitus (T2DM). There also exists an association between phosphatemia and renal impairment, the latter hampering cardiovascular function through an array of physiologic roles, such as fluid regulation, hormonal tone, and neuromodulation. Moreover, increased phosphate flux is associated with an associated increase in fibroblast growth factor 23 levels, also detrimental to homeostatic cardiometabolic function. A contemporary commentary concerning this notion unifying cardiovascular outcome trial data with the translational biology of phosphate is scant within the literature. Given the apparent beneficial outcomes associated with SGLT2i administration notwithstanding negative effects of phosphatemia, we discuss in this review the effects of phosphate on the cardiometabolic status in patients with T2DM and cardiorenal disease, as well as the mechanisms by which SGLT2i counteract or overcome them to achieve their net effects. Content drawn to develop this conversation begins with proceedings in the basic sciences and works towards clinical trial data.

Sodium-glucose co-transporter 2 inhibitors and diabetic retinopathy: insights into preservation of sight and looking beyond.

Sodium-glucose co-transporter 2 Inhibitors (SGLT2i) were initially developed as therapeutic options for patients with type 2 diabetes mellitus (T2DM). Recently, randomized clinical trials have investigated their effects in cardiorenal protection through major adverse cardiovascular event reduction and reductions in diabetic nephropathy. While multiple mechanisms are proposed for this protection, microvascular protection is the primary component of their efficacy. While not primarily emphasized in clinical trials, evidence in other studies suggests that SGLT2i may confer retinoprotective effects via some of the same mechanisms in the aforementioned cardiorenal trials. Diabetic patients are susceptible to vision loss with chronic hyperglycemia promoting inflammation, edema, and retinal pathological changes. Targeting these pathways via SGLT2i may represent opportunities for providers to decrease retinopathy in high-risk T2DM patients, reduce disease progression, and lower drug burden in diabetic retinopathy patients. Further comprehensive clinical trials investigating these associations are needed to establish the potential retinoprotective effects of SGLT2i.

The Rothman Index Does Not Predict a Successful Extubation in the Neurosurgical Critical Care Unit.

Background Identification of risk factors associated with successful extubation in neurosurgical critical care units (NSICUs) has been elusive due to the complex nature of neurocritical care injuries and patient factors. Traditional risk factors for extubation were shown to have poor predictive value in neurocritical care patients as compared to mixed ICU patients. The aim of this study was to determine if any risk factors, including the Rothman Index, could reliably predict successful extubation in a large sample size of neurocritical care patients. Methods We retrospectively analyzed 610 consecutively intubated patients in an NSICU while collecting variables of interest in airway management. Furthermore, Rothman Indices were collected immediately after intubations and extubations. A paired t-test of the immediate changes in Rothman Indices after airway manipulation was compared in patients who needed reintubation. In a smaller cohort of 88 patients, in whom complete data points existed for airway management, we performed a principal component analysis (PCA) to determine which risk factors were associated with extubation success when indexed with the magnitude of the Rothman Index. Results In 610 consecutively intubated patients, the mean pre-intubation Rothman Index average was 41.0 compared to the mean post-extubation Rothman Index was 35.4 (p<0.0001). Compared to those who were re-intubated, the Rothman Index did not correlate well with the prediction of extubation (p=0.355). Furthermore, an analysis of the PCA plot showed that a higher respiratory rate, longer length of stay, shorter length of intubation, and smaller cuff leak percentage were identified as risk factors associated with reintubation. Age and change in rapid shallow breathing index (RSBI) did not correlate with reintubation. Conclusion The Rothman Index does not predict extubation success in patients in an NSICU. Risk factors associated with reintubation were respiratory rate, length of stay, length of intubation, and cuff leak percentage. Reintubation rates in our single-center NSICU are on par with general critical care populations.

Analyzing National Incidences and Predictors of Open Conversion During Minimally Invasive Partial Nephrectomy for cT1 Renal Masses.

Objectives: To analyze predictors of open conversion during minimally invasive partial nephrectomy (MIPN) for cT1 renal masses. Methods: The National Cancer Database (NCDB) was investigated for kidney cancer patients who underwent partial nephrectomy (PN) between 2010 and 2015. Patients who underwent MIPN were stratified into converted and nonconverted groups. Sociodemographics, facility characteristics, and surgical outcomes were compared between the two groups, and multivariate logistic regression model was fitted to identify independent predictors of open conversion. Results: In total, 54,246 patients underwent PN for kidney cancer during the 6-year period. Of those, 18,994 (35%) were open partial nephrectomies (OPNs) and 35,252 (64%) were MIPN. Overall, 1010 (2.87%) of MIPNs were converted to OPN. There was an increasing utilization of MIPN from 50.35% in 2010 to 74.73% in 2015. Patients who had open conversion had more 30-day readmissions (5.95% vs 3.31%, p < 0.01). On multivariate analysis; high-volume facility (>30 MIPNs/year), year of surgery (2015 vs 2010), and robotic approach predicted a lower likelihood of conversion (odds ratio [OR] 0.52, confidence interval [CI] 0.44-0.62; OR 0.59, CI 0.47-0.73; and OR 0.31, CI 0.27-0.35; respectively, p < 0.001 for all). Conversely, Medicaid (vs private insurance; OR 1.75, CI 1.39-2.19, p < 0.001) and male sex (OR 1.26, CI 1.11-1.44, p < 0.001) were independent predictors of conversion. Conclusions: Open conversion in MIPN occurred in 2.87% of cases. There was an increasing utilization of MIPN associated with decreased conversion rates. Higher volume hospitals and progressing year of surgery were associated with less likelihood of conversion.

A focused review of cardiovascular guideline related recommendations for the primary care physician in the USA.

Primary care physicians in the USA serve the critical role of first contact for undiagnosed or mismanaged pathologies as well as providers of continuous care in multiple communities. Their scope of practice is broad from medication reconciliation to coordinating specialty care and even performing office procedures. Primary care physicians in the USA commonly encounter patients with diabetes and associated comorbidities related to prolonged insulin resistance. Mainly these include heart failure exacerbation or major adverse cardiovascular events. The demanding roles primary care physicians serve may render these providers encumbered to navigate through long, verbose and dynamic guidelines related to managing diabetes and cardiac diabetology sequelae. Our aim is to compose current, prominent evidence-based points from American medical societies such as the American College of Cardiology/American Heart Association and the American Diabetes Association central to lifestyle modifications, antiplatelet therapy, anti-hyperglycemic and SGLT2-inhibitor utilization, hypertension, dyslipidemia, and heart failure screening in a way that is both succinct and valuable to primary care physicians.

A Rare Presentation of Omental Lymphangioma Masquerading as Malignancy in an Adult Patient.

Abdominal lymphangiomas are benign vascular neoplasms of the lymphatic vessels. Most are believed to be congenital, and they rarely present in the abdomen in adults. Omental lymphangiomas, in particular, are especially rare and can masquerade as malignancy, which requires further invasive workup. We report the case of an otherwise healthy man with abdominal discomfort, ascites, and a presentation initially concerning for malignancy. However, imaging and pathologic analyses later elucidated the lesion as an omental lymphangioma requiring different management. Treatment options are either resection or sclerotherapy, and the prognosis is generally excellent.

The systemic implication of novel non-statin therapies in cardiovascular diabetology: PCSK9 as a case model.

PCSK9, like other novel non-statin drugs were primarily developed to help patients achieve low-density lipoprotein cholesterol targets, especially in patients with dyslipidemia not achieving lipid goals with statins due to poor tolerance or inadequate response. PCSK9 inhibitors, in addition to modulating lipid metabolism, improve mortality outcomes in cardiovascular disease. These benefits are markedly pronounced in patients with type 2 diabetes mellitus. However, these benefits do not come without associated risk. Multiple trials, studies, and case reports have attempted to explain observed outcomes with PCSK9 expression and administration of PCSK9 inhibitors from multiple perspectives, such as their effects on insulin sensitivity and glucose tolerance, changes in renal physiology, thyroid physiology, vascular tone, intestinal regulation of lipids, and improved cardiovascular function. These agents represent an opportunity for physicians to exercise prudence by using appropriate clinical judgement when managing comorbidities in the hyperglycemic patient, a concept that extends to other novel non-statin drugs.

ST Elevation Myocardial Infarction as Presenting Feature of C-ANCA Vasculitis: A Case of a Diagnostic Dilemma.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS). Although uncommon, it should be included in the differential diagnosis for middle-aged patients without elevated atherosclerotic vascular disease risk or a family history of cardiovascular disease. SCAD is associated with postpartum women; however, reports noting its association with autoimmune disease and vasculopathy in other populations have recently gained prominence. We report a case of a 41-year-old male who was found to have SCAD after presenting with ST segment elevation myocardial infarction in the context of episodic vision loss, and who later underwent work-up for C-ANCA vasculitis and was successfully treated with corticosteroids. LEARNING POINTS: SCAD is most common in middle-aged females. However, it can present in male patients, and it should raise suspicion of underlying vasculopathy.Eosinophilic vasculitis may mimic parasitic infection.C-ANCA vasculitis can be associated with SCAD.

Influenza: National Trends Using the National Inpatient Sample Database from 1993 to 2015.

Background There is a significant impact of influenza on individuals, families, and societies both economically and clinically. This significant impact is a result of hospital admissions, medication expenses, side effects, secondary bacterial infections, and more days off from work or other forms of reduced productivity for the patients or their caretakers. Our objective is to present the trends in the rate of hospital discharges per 100,000 population from the years 1993 through 2015, the mean age, and the inpatient mortality rate. Methods This is a retrospective study utilizing the National Inpatient Sample (NIS) from 1993 through 2015. Discharges due to influenza from 1993 to 2015 were identified, and the rate of discharges per 100,000 population, inpatient mortality, and mean age of discharged patients were trended. Linear regression was used to assess if the deviation from horizontal was statistically significant for the trends of the rate of discharges per 100,000 population, mean age, and percentage of the inpatient mortality. Result The mean age and inpatient mortality vary from year to year. The linear regression analysis for the trends was not statistically significant, and for the percentage of the inpatient mortality, the deviation from horizontal was not significant, P-value 0.75 and F-value: 0.09. Similarly, for the mean age, the deviation from horizontal was not significant with a P-value of 0.97 and an F-value of 0.001. However, the linear regression analysis for the rate of discharges per 100,000 population was remarkable for a statistically significant deviation from the horizontal with a P-value of 0.0002 and an F value of 19.5. Conclusion Recent advancements in influenza detection have made the detection feasible, quick, and cost-effective. However, the role of these advanced modalities on the outcome is still controversial. Our analysis revealed a significant increase in the rate of discharges due to influenza, but there was no significant change in the parentage of the inpatient mortality over the years between 1993 - 2015. Advanced influenza virus detection tests are now recommended in both outpatient (including emergency department) and inpatient admissions. The recent increase in inpatient admissions could be due to better detection modalities. However, no change in the percentage of inpatient mortality makes the impact of these detection tests on the outcome questionable. A further prospective study is warranted to assess the impact of these tests on the outcome.

Prosthetic mitral valve Aspergillus fumigatus endocarditis.

Aspergillus endocarditis is a fatal source of valvular infection with a near 100 % mortality rate if pharmacotherapy and valve-replacement surgery are not initiated swiftly after diagnosis. Complicating its diagnosis is the low yield for growth on standard blood culture and time requirements for molecular diagnostic tools to return a result. Aspergillus endocarditis of the mitral valve presents as valvular vegetations that reduce the caliber of the mitral valve and can cause syncope as in the case of mitral stenosis with subsequent valve failure, left atrial enlargement, and prospective cardiovascular failure. Reports of the management of Aspergillus endocarditis after serial mitral valve replacement are not prominent in the literature. We report the case of a 41-year-old female with previous mitral valve prosthesis who received a second prosthetic mitral valve after a syncopal episode. Vegetations resembling thrombi were noted on transesophageal echocardiogram, diagnosed as Aspergillus fumigatus endocarditis, and successfully treated with antifungal therapy in conjunction with removal of her dysfunctional prosthesis.

Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of drugs that were primarily developed for the treatment of type 2 diabetes mellitus. However, these agents have shown to provide additional beneficial effects. We will discuss three main topics regarding the use of SGLT2 inhibitors: noncardiovascular effects, cardiovascular benefits, and novel clinical indications. Multiple clinical trials and preliminary studies across varying disciplines have shown that these agents exhibit cardiorenal-protective benefits, retinoprotective benefits, and may aid in weight loss without causing marked hypoglycemia. Therefore, these agents represent an avenue in clinical practice to manage comorbid conditions in the hyperglycemic patient. Because of their multifaceted effects and robust action, SGLT2 inhibitors represent therapy options for providers that not only provide beneficial clinical results but also reduce total patient drug burden.