Felty Syndrome in a Patient Presenting With Bilateral Scleritis and Multiple Autoimmune Syndrome: A Case Report.

Autoimmune diseases can result in additional symptoms and complications impacting various organ systems beyond the joints. These can affect the eyes, skin, respiratory, cardiac, and renal systems. Recognizing and understanding these diverse manifestations, such as the severe eye issues seen in rheumatoid arthritis (RA) and the potentially life-threatening Felty syndrome, is crucial for clinicians to promptly identify and treat these conditions effectively. In this case presentation, we report on a patient admitted for bilateral scleritis, which was found to be secondary to multiple autoimmune syndrome type 3. During the patient's hospital stay, Felty syndrome was incidentally diagnosed due to the observed combination of RA, splenomegaly, and absolute neutropenia. Prompt recognition of this condition allowed the patient to receive appropriate care, including oral steroids, hydroxychloroquine, and methotrexate, decreasing the risk of severe complications.

Pylephlebitis-induced acute liver failure: A case report and review of literature.

BACKGROUND: Pylephlebitis is an extremely rare form of septic thrombophlebitis involving the portal vein, carrying high rates of morbidity and mortality. CASE SUMMARY: We present a case of a 42-year-old male with no past medical history who presented with acute onset of abdominal pain and altered mental status with laboratory tests demonstrating new-onset acute liver failure. Pylephlebitis was determined to be the underlying etiology due to subsequent workup revealing polymicrobial gram-negative anaerobic bacteremia and complete thrombosis of the main and left portal veins. To our knowledge, this is the first documented case of acute liver failure as a potential life-threatening complication of pylephlebitis. CONCLUSION: Our case highlights the importance of considering pylephlebitis in the broad differential for abdominal pain, especially if there are co-existing risk factors for hypercoagulability. We also demonstrate that fulminant hepatic failure in these patients can potentially be reversible with the immediate initiation of antibiotics and anticoagulation.

Improving Discharge Rates to Home With the Help of Mobility Technicians: A Step in the Right Direction.

Background Early ambulation during acute hospitalization has been associated with improved clinical outcomes for patients. Despite the benefits of mobility in the hospital setting, physical therapists and nursing staff are often constrained by time. Mobility technicians (MTs) are individuals with specialized training who have emerged as a potential solution by providing safe ambulation for patients during their hospital stay. Objectives The purpose of this quality improvement project was to investigate the impact of MTs on clinical and financial outcomes for admitted patients at a high-volume tertiary institution. Methods A quality improvement project was implemented at Jersey Shore University Medical Center, Neptune City, from October 2022 to March 2023. The study was a prospective, single-institution cohort study and included patients admitted to two medical floors. Patients were divided into an experimental group that received services from MTs and a control group that did not receive this service but was eligible based on clinical status. The primary endpoint was the proportion of patients discharged to home. Secondary outcomes included the length of stay and financial impact. Results A total of 396 admitted patients were included, with 222 patients in the MT group and 174 in the non-MT group. Patients in the MT group were discharged home more frequently, at a rate of 79.7% compared to 66.1% for patients in the non-MT group (p = 0.002). MTs contributed to an average 2.4-day reduction in the length of hospital stay (7.8 days vs. 10.2 days, p = 0.007). The MT intervention led to an estimated net savings of $148,500 during the six-month study period. Additionally, 2.9 daily hospital beds were created. Conclusion Implementing an MT program significantly increased the discharge-to-home rates and decreased hospital length of stay. Preliminary analysis suggests that this intervention is cost-effective and can assist institutions in managing increased hospital capacity strain through the creation of additional hospital beds.

A Double Hit to Ubiquitination Leading to a New Diagnosis of VEXAS Syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly defined illness that bridges hematology, oncology, and rheumatology. Its pathophysiology originates in a mutation in the UBA1 gene that leads to a defect in ubiquitination resulting in a severe systemic inflammatory syndrome. It is associated with significant morbidity and mortality; however, data are scarce due to limited cases described in the literature. Here we describe a case of a male in his 60s who was referred to hematology-oncology due to progressive dyspnea, poor oral intake, and weight loss. He was diagnosed with relapsing polychondritis 2 years prior; however, his symptoms did not improve despite treatment. He was ultimately diagnosed with VEXAS syndrome with a mutation in UBA1 (ubiquitin-like modifier activating enzyme 1) and a concurrent SQSTM1 mutation. In addition, the coexistence of two mutations in the ubiquitination pathway in the same patient has not been reported to date. This patient and the treatment course were compared to pre-existing literature to increase awareness and improve the medical management of VEXAS syndrome.

Borderline rpoB mutations transmit at the same rate as common rpoB mutations in a tuberculosis cohort in Bangladesh.

The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. So-called borderline rpoB mutations confer low-level resistance, in contrast to more common rpoB mutations which confer high-level resistance. While some borderline mutations show lower fitness in vitro than common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44 % of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8 %) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages two, three, and four relative to lineage one. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.

CaMKK2 is not involved in contraction-stimulated AMPK activation and glucose uptake in skeletal muscle.

OBJECTIVE: The AMP-activated protein kinase (AMPK) gets activated in response to energetic stress such as contractions and plays a vital role in regulating various metabolic processes such as insulin-independent glucose uptake in skeletal muscle. The main upstream kinase that activates AMPK through phosphorylation of α-AMPK Thr172 in skeletal muscle is LKB1, however some studies have suggested that Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) acts as an alternative kinase to activate AMPK. We aimed to establish whether CaMKK2 is involved in activation of AMPK and promotion of glucose uptake following contractions in skeletal muscle. METHODS: A recently developed CaMKK2 inhibitor (SGC-CAMKK2-1) alongside a structurally related but inactive compound (SGC-CAMKK2-1N), as well as CaMKK2 knock-out (KO) mice were used. In vitro kinase inhibition selectivity and efficacy assays, as well as cellular inhibition efficacy analyses of CaMKK inhibitors (STO-609 and SGC-CAMKK2-1) were performed. Phosphorylation and activity of AMPK following contractions (ex vivo) in mouse skeletal muscles treated with/without CaMKK inhibitors or isolated from wild-type (WT)/CaMKK2 KO mice were assessed. Camkk2 mRNA in mouse tissues was measured by qPCR. CaMKK2 protein expression was assessed by immunoblotting with or without prior enrichment of calmodulin-binding proteins from skeletal muscle extracts, as well as by mass spectrometry-based proteomics of mouse skeletal muscle and C2C12 myotubes. RESULTS: STO-609 and SGC-CAMKK2-1 were equally potent and effective in inhibiting CaMKK2 in cell-free and cell-based assays, but SGC-CAMKK2-1 was much more selective. Contraction-stimulated phosphorylation and activation of AMPK were not affected with CaMKK inhibitors or in CaMKK2 null muscles. Contraction-stimulated glucose uptake was comparable between WT and CaMKK2 KO muscle. Both CaMKK inhibitors (STO-609 and SGC-CAMKK2-1) and the inactive compound (SGC-CAMKK2-1N) significantly inhibited contraction-stimulated glucose uptake. SGC-CAMKK2-1 also inhibited glucose uptake induced by a pharmacological AMPK activator or insulin. Relatively low levels of Camkk2 mRNA were detected in mouse skeletal muscle, but neither CaMKK2 protein nor its derived peptides were detectable in mouse skeletal muscle tissue. CONCLUSIONS: We demonstrate that pharmacological inhibition or genetic loss of CaMKK2 does not affect contraction-stimulated AMPK phosphorylation and activation, as well as glucose uptake in skeletal muscle. Previously observed inhibitory effect of STO-609 on AMPK activity and glucose uptake is likely due to off-target effects. CaMKK2 protein is either absent from adult murine skeletal muscle or below the detection limit of currently available methods.

Role of Plasmapheresis in Hemolysis, Elevated Liver Enzymes and Low Platelets (HELLP) Syndrome.

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a rare abnormality comprising a series of symptoms that make up a syndrome. It usually happens during pregnancy or right after delivery. We describe a case of a 31-year-old female G4P2A2 (Gravida 4 Para 2 Abortions 2) who presented to the hospital for normal vaginal delivery but immediately postpartum developed HELLP syndrome. Acute fatty liver of pregnancy was a differential that the patient also met the criteria for. Her condition improved after starting her on plasmapheresis without considering hepatic transplantation. We emphasize distinguishing the overlap of symptoms between HELLP syndrome vs. acute fatty liver of pregnancy and the outcomes of plasmapheresis in managing HELLP syndrome without needing hepatic transplantation.

Ominous Sign of Pneumatosis Intestinalis With Portal Venous Gas.

The presence of gas and free air in the extraluminal space of the intestines is known as pneumatosis intestinalis (PI). There are many different causes of this finding, including gastrointestinal, pulmonary, autoimmune, and many more. It is often difficult to differentiate the etiology and clinical importance of the radiographic evidence on pneumatosis intestinalis due to the unclear pathophysiology causing the disease. To complicate things further, the ominous sign of portal venous gas poses the question of whether surgical intervention is needed. We report two cases both with clinical and radiographic evidence of secondary pneumatosis intestinalis with an associated sinister finding of portal venous gas. The cases differ by urgent surgical intervention versus observation before surgery. In this case series, we emphasize the importance of recognizing the radiographic finding and stress the need for further research to standardize a plan of care, including indications for surgery. We encourage more cases like this to be reported to aid in diagnosing and treating this condition early on with the aim of improving the mortality associated with it.

Comparative Study of Three Biological Control Agents and Two Conventional Fungicides against Coriander Damping-off and Root Rot Caused by Rhizoctonia solani.

The in vitro and in vivo efficacy of three biocontrol agents, Trichoderma viride, Pseudomonas fluorescence, and Bacillus subtilis, were tested against Rhizoctonia solani (AG-4) infection compared to two conventional fungicides (Rizolex-T 50%wettable powder and Amistar 25%). Antifungal enzyme activity was assayed in the culture filtrate of the biocontrol agents. The impact of the tested biocontrol agents on the induction of the coriander immune system was investigated against R. solani by assessing the resistance-related enzymes and compounds in biocontrol agent-treated plants compared with the control. The obtained results revealed that all tested biocontrol agents significantly reduced the linear growth of R. solani, and T. viride recorded the highest inhibition percentage. This could be linked to the ability of T. viride to produce higher activities of antimicrobial enzymes, i.e., cellulase, chitinase, and protease, compared to P. fluorescence and B. subtilis. Applying the tested biocontrol agents significantly alleviated pre- and post-emergence damping-off and root rot/wilt diseases of infected coriander compared with untreated plants. The tested biocontrol agents exhibited significantly higher germination percentage and vigor index of the coriander than the tested fungicides. The tested biocontrol agents significantly minimized the reduction of photosynthetic pigments induced by R. solani. In addition, the results showed a significant increase in enzymes/molecules (i.e., phenylalanine, catalase, peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, phenolics, ascorbic acids, and salicylic acid) involved directly and indirectly in coriander resistance to R. solani. The principal component analysis of the recorded data recommended the role of the high accumulation of oxidative parameters (hydrogen peroxide and lipid peroxidation) and the inhibition of phenolic compounds in the downregulation of coriander resistance against R. solani. The heatmap analysis results revealed that biocontrol agents, especially Trichoderma, enhanced the resistance against R. solani via the stimulation of salicylic acid, phenolics, and antioxidant enzymes. Overall, the data recommended the efficacy of biocontrol agents, especially T. viride, against R. solani infecting coriander plants, which could be an efficient and a safer alternative to conventional fungicides.

Hemophilia B: A Pain in the Back.

This case report describes an unusual manifestation of hemophilia B, in the form of a lateral chest wall hematoma. A 27-year-old hemophiliac male was found to have a lateral chest wall hematoma after presenting with back pain associated with localized chest wall swelling. Even more unusual than the location of his hematoma was the absence of any preceding triggers such as a fall or trauma to the area. To our knowledge, this is the first reported case of its kind in a patient with inherited hemophilia B. We believe the reporting of such rare presentations increases awareness of these possibilities and thus aids in the prompt diagnosis and treatment of other similar cases when they are encountered.

Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.

Naphthyridine-based inhibitors were synthesized to yield a potent and cell-active inhibitor of casein kinase 2 (CK2). Compound 2 selectively inhibits CK2α and CK2α' when profiled broadly, thereby making it an exquisitely selective chemical probe for CK2. A negative control that is structurally related but lacks a key hinge-binding nitrogen (7) was designed on the basis of structural studies. Compound 7 does not bind CK2α or CK2α' in cells and demonstrates excellent kinome-wide selectivity. Differential anticancer activity was observed when compound 2 was profiled alongside a structurally distinct CK2 chemical probe: SGC-CK2-1. This naphthyridine-based chemical probe (2) represents one of the best available small molecule tools with which to interrogate biology mediated by CK2.

Appendiceal Bulge on Routine Colonoscopy: Not All Disease Is Luminal.

Appendiceal mucocele is an extremely rare pathology accounting for 0.3-0.7% of all appendiceal pathology. It is characterized by appendiceal lumen dilatation by mucinous secretion collection. Though abdominal imaging and tissue Biopsy aids in diagnosis, suspicion should arise when a slight bulge or protrusion is seen on colonoscopy. We present a case of incidental appendiceal bulge found on a routine colonoscopy to evaluate abdominal pain that led to prompt diagnosis and management of appendiceal mucocele.

Triple Jeopardy: Rapidly Progressive Glomerulonephritis Induced by Triple Seropositive Disease-A Rare Case.

The double-positive disease is the co-occurrence of antiglomerular basement membrane (anti-GBM) disease and antineutrophil cytoplasmic antibodies (ANCAs) and is an uncommon cause of renal failure. Our case of triple-positive disease is an even rarer cause of isolated renal failure, as it includes anti-GBM, antimyeloperoxidase (MPO), and antiproteinase 3 (PR3). We present a case of a 62-year-old Caucasian male with a history of multiple comorbidities, who presented to the emergency department (ED) with worsening dyspnea on exertion that started about one month prior to admission. He was found to be in renal failure secondary to triple-positive disease. We believe that the likely mechanism of our patient's triple-positive disease was a drug-induced ANCA vasculitis overlapping with Goodpasture's syndrome. We believe our case to be a valuable addition to the literature as it is a rare overlap syndrome without a previously established disease course or etiology.

A Unique Presentation of Extrapulmonary Legionella: Rhabdomyolysis-Induced Acute Renal Failure and Cerebellar Dysfunction.

Legionella is most known for causing pneumonia. However, it is a systemic disease that can directly cause severe multi-organ injury in what is sometimes referred to as "extrapulmonary Legionella." In this case report, a reasonably healthy 80-year-old man is found to have Legionella pneumonia complicated by rhabdomyolysis with acute, severe, non-oliguric acute kidney injury, uremic encephalopathy, transaminitis, and cerebellar dysfunction. With a 14-day course of azithromycin and prompt initiation of dialysis, the patient's pneumonia and systemic sequelae improved. This case demonstrates the importance of considering Legionella in the differential diagnosis of patients who present with community-acquired pneumonia and multi-organ dysfunction. Prompt diagnosis and management may decrease mortality associated with this disease sequela.

Modifying Beauty Is Not Priceless: A Rare Case of Silicone-Induced Hypercalcemia With Renal Failure.

Silicone implant-induced hypercalcemia is a rather rare pathological entity. There are only a few published reports on the topic. Here, we have reported a case of acute kidney injury in the background of hypercalcemia and elevated vitamin D level in a transgender patient with a history of silicone injections in the breast and buttocks for cosmetic purposes.

Rare Overlap of Granulomatosis With Polyangiitis in a Patient With Rheumatoid Arthritis.

Granulomatosis with polyangiitis (GPA) is a systemic small/medium-sized vessel vasculitis, which is a member of the family of antineutrophil cytoplasmic auto-antibody-associated vasculitides. This disorder affects multiple organs as it is a systemic disease, but overlapping with rheumatoid arthritis is extremely rare, with few cases reported in the medical literature. We report a case of a 55-year-old female with a history of rheumatoid arthritis who presented with recurrent upper/lower respiratory tract symptoms that responded poorly to antibiotics. The patient had elevated antiproteinase antibodies, ANCA IgG titer with a cytoplasmic staining pattern, proteinuria, hematuria, chest imaging showing cavitating and non-cavitating masses, and biopsies of lung and nasal tissue confirming the diagnosis of GPA. Our patient was given immunosuppressant therapy and improvement in lab work and clinical symptoms were seen throughout the course of treatment. This case report is unique as GPA usually rarely presents with rheumatoid arthritis (RA), but in this case, the patient had a history of rheumatoid arthritis with a new biopsy-proven GPA. This case report will help future physicians to better diagnose similar cases and help to facilitate clinical recognition and treatment for the same.

Inpatient glycemic control and outcome of COVID-19 patients: A retrospective cohort.

OBJECTIVES: Although there have been associations between diabetes and mortality in COVID-19 patients, it is unclear whether this is driven by the disease itself or whether it can be attributed to an inability to exhibit effective glucose control. METHODS: We conducted a retrospective cohort study of 292 patients admitted to a tertiary referral center to assess the association of mortality and glycemic control among COVID-19-positive patients. We used a logistic regression model to determine whether average fasting glycemic levels were associated with in-hospital mortality. RESULTS: Among the diabetic and non-diabetic patients, there were no differences between mortality or length of stay. Mean glucose levels in the first 10 days of admission were higher on average among those who died (150-185 mg/dL) compared with those who survived (125-165 mg/dL). When controlling for multiple variables, there was a significant association between mean fasting glucose and mortality (odds ratio = 1.014, p < 0.001). The associations between glucose and mortality remained when controlled for comorbidities and glucocorticoid use. CONCLUSION: The results of this retrospective study show an association between mortality and inpatient glucose levels, suggesting that there may be some benefit to tighter glucose control in patients diagnosed with COVID-19.

Large Vessel Stroke Following Multiple Other Strokes and Cardiomyopathy in a Forty-Nine-Year-Old COVID-19 Patient.

The novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made its presence known on the centerstage of worldwide healthcare in 2020. Although it is widely known about its pulmonary presence and ensuing complications, evidence is emerging that there are other organ systems including the cardiovascular and cerebrovascular systems that may be damaged by this virus. There have been reports of large vessel stroke occurring in coronavirus disease 2019 (COVID-19) positive patients, with very few reported in the age group less than 50 years. In this case, we describe a previously healthy 49-year-old male who presented with signs of stroke, and was found to have the novel coronavirus as he had been suffering from upper respiratory tract symptoms for 3 weeks. He subsequently developed further large vessel stroke while in the hospital despite being started on antiplatelet therapy. He was also found to have new onset cardiomyopathy. He was started on anticoagulation and discharged with follow-up for cardiomyopathy testing outpatient. This case begs the question on which anticoagulation to utilize in COVID-19 positive patients to be effective in preventing thrombotic events. It is postulated that a pro-inflammatory state induced by the virus and the virus' affinity for angiotensin converting enzyme-2 receptors in the cerebral vasculature are predispositions to cause a stroke. The virus also directly damages cardiac myocytes causing a number of cardiac complications including cardiomyopathy. It is crucial that guidelines on anticoagulation choice and indications for when to start anticoagulation be developed in order to prevent the more devastating consequences of thrombosis and embolism and their subsequent clinical sequelae.

Trends of Ordering Hypercoagulability Work-Up at an Academic Medical Center.

BACKGROUND: Venous thromboembolism is a significant clinical event, with an annual incidence of 1-2 per 1000 population. Risk factors include recent surgery, prolonged immobility, oral contraceptive use, and active cancer. Inherited risks include protein C and S deficiencies, antithrombin deficiency, factor V Leiden mutation and prothrombin. These factors can be tested to guide therapy, but current evidence suggests that testing for inherited thrombophilia is not recommended in most inpatient settings. In the era of high value care, hypercoagulable testing for VTE creates a financial burden for the hospital and patients. We performed a retrospective chart review of hypercoagulable orders on VTE patients at our institution. METHODS: Institutional Review Board approval was obtained. A total of 287 adult patients admitted over a 3-month period with the diagnosis of VTE were included. Patients were identified via ICD-10 codes and data were collected from electronic medical records. Patient characteristics, provoked versus unprovoked VTE, and relative contraindications for hypercoagulability work-up were analyzed. Our primary outcome was to assess the appropriateness of thrombophilia testing in VTE patients based on screening guidelines. Our secondary outcome was to analyze the cost burden of ordering these tests. RESULTS: A total of 287 patients were included in our data analysis. Patient risk factors for VTE were malignancy, previous DVT, immobilization, surgery 3 months prior, and central line placement. Fifty-seven of 287 patients had at least one hypercoagulable test ordered during hospitalization which did not adhere to guidelines. Misuse of testing occurred during active thrombosis, active anticoagulation, presence of risk factors, first episode of VTE, and malignancy. The cost of ordering these 5 thrombophilia tests totaled over $40,000. CONCLUSION: In our study, numerous patients were tested without compliance to standard recommendations, which created financial and value-based burdens on our health care system. Increased awareness among clinicians is thus warranted to ensure high value care.

Outcomes of Renal Function in Cardiogenic Shock Patients With or Without Mechanical Circulatory Support.

BACKGROUND: The objective of the study was to compare the renal outcomes in patients presenting with all-cause cardiogenic shock who were supported by either Impella devices (Abiomed, Danvers, MA), intra-aortic balloon pump (IABP), or vasopressors alone. Outcomes of cardiogenic shock remain poor even with the advancement of early revascularization and circulatory supportive care. Percutaneous mechanical circulatory support (MCS) device has emerged as an effective strategy in protecting end organ function especially renal function during high risk percutaneous coronary intervention (PCI) and in patients with cardiogenic shock. Currently, comparative data amongst various MCS modalities and their association with improvement of renal function in cardiogenic shock patients have not been well characterized. METHODS: Data from New Jersey Cardiac Catheterization Data registry of cardiogenic shock patients from a single tertiary care institution that underwent cardiac catheterization and the modality used to treat were obtained, either with Impella devices, IABP, or treatment with vasopressors alone. Retrospective chart review was conducted to assess the incidence of acute kidney injury (AKI) on patients with cardiogenic shock prior to and after cardiac catheterization and renal function was evaluated over the course of 96 h after cardiac catheterization. Statistical analysis was performed to ascertain significant difference in creatinine and estimated glomerular filtration rate (eGFR) in patients who received Impella devices, IABP, or were treated with vasopressors alone. RESULTS: A total of 61 all-cause cardiogenic shock patients met the inclusion and exclusion criteria and were included in the study with 19 receiving IABPs, 15 receiving Impella devices, and 27 treated with vasopressors alone. Baseline characteristics among these three groups did not show any statistically significant difference. A total of 29 cardiogenic shock patients had experienced AKI prior to cardiac catheterization in which those receiving Impella devices showed statistically significant decrease in creatinine and increase in eGFR at 72 and 96 h (P < 0.05) compared to baseline. Within the same cohort, Impella group showed statistically significant lower creatinine at 96 h when compared to IABP. Patients that experienced AKI after cardiac catheterization did not show any statistically significant changes in renal function regardless of modality used. CONCLUSION: The results of our study suggest that Impella devices improve renal function in all-cause cardiogenic shock patients who experience AKI prior to undergoing cardiac catheterization.