Spindle Cell Carcinoma Presenting as a Massive Pleural Effusion.

The lung's sarcomatoid carcinomas (SC) are a heterogeneous sporadic group of non-small cell lung carcinomas (NSCLCs) and are very challenging to diagnose and treat. Spindle cell carcinoma (SpCC) is a very rare subset of this group. Hence, the prognosis and treatments are unclear due to the limited literature available. The presentation of this cancer varies based on the site of the neoplasm and the complications and metastases observed at the time of diagnosis. Here, we report a 73-year-old man who presented to the emergency room after two months of worsening dyspnea and fatigue. Chest X-ray showed an extensive left-sided pleural effusion. A computed tomography (CT) scan of the chest showed a pleural-based mass that came back as SpCC, for which he was referred to a university hospital.

Achieving superficial femoral venous access in a critically ill COVID-19 patient in the prone position.

A 63-year-old obese male was admitted with acute respiratory failure secondary to COVID-19. Day 13 the patient decompensated, lapsing into a critical stage of severe acute respiratory distress syndrome, requiring immediate prone positioning. The Rapid Response Team managed the emergency intervention for intubation but was unable to establish central access with the patient in the prone position. A consult to the Vascular Access Team succeeded in establishing central catheter placement with an ultrasound-guided mid-thigh superficial femoral 55-centimeter triple lumen catheter. The terminal tip of the catheter was confirmed in the mid portion of the inferior vena cava.

Hypoglycemia-Induced Basal Ganglia Infarct: A Rare Case of Metformin Toxicity in a Hemodialysis Patient.

Metformin is the preferred agent in type 2 diabetes due to its efficacy, safety profile, cardioprotective benefits, weight loss, and accessibility in the market. However, Metformin should be prescribed with caution in patients with renal dysfunction and is contraindicated in those with a glomerular filtration rate (GFR) of less than 30 mL/min. Though extremely rare, accumulation of metformin due to poor renal clearance can cause metformin toxicity and subsequently cause lactic acidosis and hypoglycemia. The incidence is estimated at less than 10 events per 100,000 patients. Hypoglycemia has been shown to induce ischemic strokes in previous case reports; however, only one other case control study has shown hypoglycemia-induced strokes in the setting of metformin toxicity. Herein, we present a rare case of hypoglycemia-induced ischemic stroke from metformin toxicity, in a patient undergoing maintenance hemodialysis. Our case report illustrates an extremely rare case of metformin toxicity that caused a hypoglycemic-induced ischemic infarct.

Searching for the Culprit: When Diabetic Ketoacidosis Presents With Insulin Autoantibodies.

OBJECTIVE: The main objective was to describe and review a unique case that presented with diabetic ketoacidosis, positive insulin autoantibodies (IAAbs, which are found in Hirata disease and are usually present with hypoglycemia), and laboratory findings characteristic of type B insulin resistance syndrome (TBIRS) and systemic lupus erythematosus. Confirmation of TBIRS was obtained in Germany as immunoassay for insulin receptor antibodies (IRAbs) is not available in the United States. METHODS: A literature review on TBIRS and cases that present with IAAbs and IRAbs simultaneously was conducted. RESULTS: We found 6 cases presenting with hypoglycemia, both antibodies, and treatment attempts with various management approaches that were different from the proposed National Institutes of Health (NIH) protocol for TBIRS. Our case is distinct because of the demographic background, presentation with diabetic ketoacidosis, comparatively lower insulin requirement, and no significant hypoglycemic episodes in the third phase. CONCLUSION: We propose that access to IRAb immunoassays may be important for diagnosing milder cases of TBIRS, while IAAbs may provide prognostic and therapeutic insights. Despite completely different presentation from other TBIRS patients reviewed, we observed that the proposed NIH protocol consisting of dexamethasone, rituximab, and cyclophosphamide was successfully employed in our patient. Thus, we propose that our case and the findings regarding antibody testing and the NIH treatment regimen may assist clinicians with earlier recognition and effective management of milder cases of TBIRS.

Unusual Presentation of Methicillin-Resistant Staphylococcus aureus Colitis Complicated with Acute Appendicitis.

Clostridium difficile colitis has been the most recognized bacterial enterocolitis for years and other bacteria such as Staphylococcus colitis has been relegated. Staphylococcus enterocolitis following antibiotics had been one of the most frequent complications in surgical patients in the 1950s and 1960s and now reappear with more resistance such as methicillin-resistantStaphylococcus aureus(MRSA) colitis which brings a new challenge. A 32-year-old Hispanic female with a history of type I diabetes mellitus presenting with altered sensorium and a 2-day history of watery, nonbloody diarrhea, intractable emesis, and diffuse crampy abdominal pain. About a month before the presentation, the patient had a soft-tissue laceration on the left foot requiring a 7-day course of cephalexin and clindamycin that healed appropriately. On physical examination, she was tachycardic with heart rate of 110 bpm and tachypneic with respiratory rate of 28, somnolent but arousable with the Glasgow Coma Scale >12. The abdomen was soft, tender diffusely to palpation without rebound or guarding. On the biochemical analysis, her blood glucose was 968 mg/dL with anion gap metabolic acidosis (AG 46). In the intensive care unit, she initiated on intravenous (IV) fluids, insulin, and IV antibiotics for suspicion of colitis. Clostridium difficile testing was negative, but stool cultures grew MRSA for which she was started on vancomycin and TMP-SMX. Due to continued abdominal pain on antibiotics, computed tomography of the abdomen with contrast showed acute appendicitis with inflammatory debris and without perforation or abscess requiring laparoscopic appendectomy. Our case presented with diabetic ketoacidosis (DKA), which complicates the etiology of abdominal pain on admission for the clinician masking-MRSA colitis associated with a rare complication of appendicitis double challenge and difficult to diagnose as most DKA patients present with abdominal pain. This is the first case report describing MRSA enterocolitis in patient with DKA complicated by acute appendicitis.

Thyrotoxic periodic paralysis after urethral dilatation.

Thyrotoxic periodic paralysis (TPP) is a rare and serious manifestation of thyrotoxicosis that causes flaccid paralysis. In severe cases, it can be life-threatening due to respiratory failure and cardiac arrhythmias. TPP is due to increased sodium/potassium ATPase activity during thyrotoxic states, which is due to mutations encoding potassium channels. It is precipitated by situations that cause a surge in catecholamines, insulin, or both. It can be treated with potassium supplementation and nonselective beta blockers, and it can be prevented by establishing euthyroid state. With the increasing numbers of outpatient procedures performed nowadays and the stress related to these procedures, patients with TPP may develop paralysis after these procedures, so clinicians should be aware of this condition and the importance of identifying it in patients presenting with flaccid paralysis.

A review of the characteristics and outcomes of 900 COVID-19 patients hospitalized at a Tertiary Care Medical Center in New Jersey, USA.

INTRODUCTION: There is a paucity of literature surrounding the in-hospital mortality and associated risk factors among coronavirus disease 2019 (COVID-19) affected patient populations in our geographical area, northern New Jersey. MATERIAL AND METHODS: A retrospective observational cohort study was performed in a tertiary care academic medical center with two locations in Paterson and Wayne serving Passaic County in northern New Jersey. The study included all 900 patients with a positive reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swab sample for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) viral test. We determined the in-hospital 75-day mortality of patients treated in the intensive care unit (ICU) compared to the medical-surgical floor unit. RESULTS: Overall in-hospital 75-day mortality was 40.7% (n = 367). The ICU group had a 77.1% (n = 237) mortality and the floor group a 21.9% (n = 130) mortality. The ICU group of patients had a higher incidence of cardiac injury, acute renal injury, liver failure, vasopressor use and the elevation of serum markers: ferritin, lactate dehydrogenase, interleukin 6 (IL-6), D-dimer, procalcitonin, and C-reactive protein compared to the floor group. Multiple logistic regression analyses revealed that age > 65 years, elevated IL6, acute renal injury, cardiac injury, and invasive mechanical ventilation were risk factors associated with mortality. CONCLUSIONS: Age > 65 years, elevated IL6, acute renal injury, cardiac injury, and invasive mechanical ventilation were risk factors associated with mortality in our COVID-19 patients.

A rare case of hypokalemic ventricular tachycardia in a patient with thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis (TPP) is a potentially fatal complication of hyperthyroidism, characterized by recurrent muscle paralysis and hypokalemia. We present a case of a 32-year-old apparently healthy male patient, who presented with acute paraparesis associated with hypokalemia (K: 1.6 mmol/L), complicated by ventricular tachycardia (VT). Advanced cardiac life support was initiated with an amiodarone infusion, and eventually QRS complex narrowed and wide complex tachycardia resolved. Intravenous potassium chloride (KCl) 40 mEq over 2-3 h and oral KCL 40 mEq were administered to treat the electrolyte imbalance. Patient paralysis was quickly reversed; motor function was regained with movement of the lower extremities. This case highlights the importance of early recognition and prompt treatment of TPP as a differential diagnosis for muscle weakness, especially in the setting of severe hypokalemia. It is important to pay attention to the possibility of the development of lethal VT associated with hypokalemia in the setting of hyperthyroidism and thyrotoxic paralysis.

An Unusual Benign Cause of an Alarming Finding on Chest-X ray: A Case Report of Widened Mediastinum due to Rare Congenital Abnormality (Azygos Vein Continuation of Inferior Vena Cava).

Acute widened mediastinum is an alarming finding. It has many possible differential diagnoses; aortic dissection (AD) is considered one that carries catastrophic outcomes. AD is relatively uncommon; it requires early and accurate diagnosis and treatment for better patient survival. However, acute mediastinal widening also can be present in more benign conditions. We report a case of a 50-year-old African American female with postoperative shortness of breath; initial imaging studies revealed an acute widened mediastinum, but on further management with diuresis and follow-up imaging, she was diagnosed with azygous vein continuation of the Inferior vena cava (IVC). This is considered as a rare benign cause of wide mediastinum. Clinicians must be aware of the presence of such a benign cause when dealing with acute wide mediastinum.

Successful Use of Renal Replacement Therapy for Refractory Hypokalemia in a Diabetic Ketoacidosis Patient.

A 39-year-old African-American female presented to the emergency department with a seven-day history of right upper quadrant abdominal pain accompanied by nausea, vomiting, and diarrhea. She was noted to be alert and following commands, but tachypneic with Kussmaul respirations; and initial laboratory testing supported a diagnosis of diabetic ketoacidosis (DKA) and hypokalemia. To avoid hypokalemia-induced arrhythmias, insulin administration was withheld until a serum potassium (K) level of 3.3 mEq/L could be achieved. Efforts to increase the patient's potassium level via intravenous repletion were ineffectual; hence, an attempt was made at more aggressive potassium repletion via hemodialysis using a 4 mEq/L K dialysate bath. The patient was started on Aldactone and continuous veno-venous hemodialysis (CVVH) with ongoing low-dose insulin infusion. This regimen was continued over 24 h resulting in normalization of the patient's potassium levels, resolution of acidosis, and improvement in mental status. Upon resolution of her acidemia, the patient was transitioned from insulin infusion to treatment with a subcutaneous insulin aspart and insulin detemir, and did not experience further hypokalemia. Considering our success, we propose CVVH as a tool for potassium repletion when aggressive intravenous (IV) repletion has failed.

Diffuse pulmonary infiltrates: A guise of adenocarcinoma.

Small and non-small cell lung cancer present in a variety of radiologic and clinical patterns, and have been linked to smoking. Primary adenocarcinoma of the lung has been increasingly recognized in females and nonsmokers, often presenting a diagnostic challenge. In the absence of smoking history, these radiographic patterns may be initially misdiagnosed as an infectious or inflammatory condition, often delaying the diagnosis of malignancy. We report two cases of female patients with relatively short or no smoking history presenting with diffuse pulmonary infiltrates not typically seen in primary lung cancer, which created a diagnostic challenge, ultimately diagnosed as primary lung adenocarcinoma. Each case had different subtype patterns of adenocarcinoma. The first case described adenocarcinoma of mostly acinar pattern; while the second case was noted to have adenocarcinoma of micropapillary pattern. Given lung adenocarcinoma's nonspecific presentation, which may mimic infectious and diffuse interstitial lung disease, the above cases highlight the importance of entertaining lung adenocarcinoma as part of the differential diagnosis of such presentations.

MGMT enrichment and second gene co-expression in hematopoietic progenitor cells using separate or dual-gene lentiviral vectors.

The DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT) allows efficient in vivo enrichment of transduced hematopoietic stem cells (HSC). Thus, linking this selection strategy to therapeutic gene expression offers the potential to reconstitute diseased hematopoietic tissue with gene-corrected cells. However, different dual-gene expression vector strategies are limited by poor expression of one or both transgenes. To evaluate different co-expression strategies in the context of MGMT-mediated HSC enrichment, we compared selection and expression efficacies in cells cotransduced with separate single-gene MGMT and GFP lentivectors to those obtained with dual-gene vectors employing either encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) or foot and mouth disease virus (FMDV) 2A elements for co-expression strategies. Each strategy was evaluated in vitro and in vivo using equivalent multiplicities of infection (MOI) to transduce 5-fluorouracil (5-FU) or Lin(-)Sca-1(+)c-kit(+) (LSK)-enriched murine bone marrow cells (BMCs). The highest dual-gene expression (MGMT(+)GFP(+)) percentages were obtained with the FMDV-2A dual-gene vector, but half of the resulting gene products existed as fusion proteins. Following selection, dual-gene expression percentages in single-gene vector cotransduced and dual-gene vector transduced populations were similar. Equivalent MGMT expression levels were obtained with each strategy, but GFP expression levels derived from the IRES dual-gene vector were significantly lower. In mice, vector-insertion averages were similar among cells enriched after dual-gene vectors and those cotransduced with single-gene vectors. These data demonstrate the limitations and advantages of each strategy in the context of MGMT-mediated selection, and may provide insights into vector design with respect to a particular therapeutic gene or hematologic defect.

Cotransduction with MGMT and Ubiquitous or Erythroid-Specific GFP Lentiviruses Allows Enrichment of Dual-Positive Hematopoietic Progenitor Cells In Vivo.

The P140K point mutant of MGMT allows robust hematopoietic stem cell (HSC) enrichment in vivo. Thus, dual-gene vectors that couple MGMT and therapeutic gene expression have allowed enrichment of gene-corrected HSCs in animal models. However, expression levels from dual-gene vectors are often reduced for one or both genes. Further, it may be desirable to express selection and therapeutic genes at distinct stages of cell differentiation. In this regard, we evaluated whether hematopoietic cells could be efficiently cotransduced using low MOIs of two separate single-gene lentiviruses, including MGMT for dual-positive cell enrichment. Cotransduction efficiencies were evaluated using a range of MGMT : GFP virus ratios, MOIs, and selection stringencies in vitro. Cotransduction was optimal when equal proportions of each virus were used, but low MGMT : GFP virus ratios resulted in the highest proportion of dual-positive cells after selection. This strategy was then evaluated in murine models for in vivo selection of HSCs cotransduced with a ubiquitous MGMT expression vector and an erythroid-specific GFP vector. Although the MGMT and GFP expression percentages were variable among engrafted recipients, drug selection enriched MGMT-positive leukocyte and GFP-positive erythroid cell populations. These data demonstrate cotransduction as a mean to rapidly enrich and evaluate therapeutic lentivectors in vivo.

Derivation of a myeloid cell-binding adenovirus for gene therapy of inflammation.

The gene therapy field is currently limited by the lack of vehicles that permit efficient gene delivery to specific cell or tissue subsets. Native viral vector tropisms offer a powerful platform for transgene delivery but remain nonspecific, requiring elevated viral doses to achieve efficacy. In order to improve upon these strategies, our group has focused on genetically engineering targeting domains into viral capsid proteins, particularly those based on adenovirus serotype 5 (Ad5). Our primary strategy is based on deletion of the fiber knob domain, to eliminate broad tissue specificity through the human coxsackie-and-adenovirus receptor (hCAR), with seamless incorporation of ligands to re-direct Ad tropism to cell types that express the cognate receptors. Previously, our group and others have demonstrated successful implementation of this strategy in order to specifically target Ad to a number of surface molecules expressed on immortalized cell lines. Here, we utilized phage biopanning to identify a myeloid cell-binding peptide (MBP), with the sequence WTLDRGY, and demonstrated that MBP can be successfully incorporated into a knob-deleted Ad5. The resulting virus, Ad.MBP, results in specific binding to primary myeloid cell types, as well as significantly higher transduction of these target populations ex vivo, compared to unmodified Ad5. These data are the first step in demonstrating Ad targeting to cell types associated with inflammatory disease.

Power-law eigenvalue density, scaling, and critical random-matrix ensembles.

We consider a class of rotationally invariant unitary random matrix ensembles where the eigenvalue density falls off as an inverse power law. Under a scaling appropriate for such power-law densities (different from the scaling required in Gaussian random matrix ensembles), we calculate exactly the two-level kernel that determines all eigenvalue correlations. We show that such ensembles belong to the class of critical ensembles.

Serum magnesium levels and acute exacerbation of chronic obstructive pulmonary disease: a retrospective study.

A decrease in serum Mg(+2) is associated with airway hyper-reactivity and impaired pulmonary function. The purpose of this study was to determine if decreased serum Mg(+2) levels in patients with chronic obstructive pulmonary disease (COPD) are associated with acute exacerbations. In a retrospective study, the charted serum Mg(+2) levels in 100 COPD patients were examined. These included 50 patients who presented with an acute exacerbation of COPD and 50 stable patients. Chart review was sequential within both groups. Serum Mg(2+) levels in the stable COPD patients averaged 0.91+/- 0.10 mmol/L (mean+/- SD) with a 95% CI of 0.88 - 0.94 mmol/L. Patients undergoing an exacerbation had significantly lower serum Mg(+2) levels (0.77+/- 0.10 mmol/L; CI, 0.74 - 0.79; p<0.0001). Logistic regression of the dichotomous outcomes as a function of serum Mg(+2) concentration demonstrated a highly significant association (chi(2)=41.26; p<10(-5)). These data were subjected to receiver-operator characteristic (ROC) analysis for decision levels (DL) and the area under the ROC curve was determined to be 0.85+/- 0.04 (CI, 0.78 - 0.93). The optimum DL was determined to lie between 0.80 mmol/L (OR=14.33; sensitivity 70%; specificity 86%) and 0.84 mmol/L (OR=11.16; sensitivity 84%; specificity 68%). These data suggest that at the lower range of the reference interval, serum Mg(+2) levels are associated with an increased risk of exacerbation of symptoms in COPD patients. Furthermore, they suggest a DL that is useful for predicting clinical outcomes in these patients and serving as a target value for therapy.