An observational study on the use of long acting buprenorphine (Sublocade) and a Tamper resistant PICC for Outpatient IV antibiotic administration in Patients with serious infections and Opioid Use Disorder; The STOP OUD project.

What is STOP OUD?: The STOP OUD project is an observational study on the use of long-acting buprenorphine (Sublocade) and a Tamper resistant PICC clamp for Outpatient IV antibiotic administration in Patients with serious infections and Opioid Use Disorder (STOP OUD). Background: The US opioid crisis is driving up serious infections related to intravenous drug use. These infections require prolonged courses of antibiotics, often resulting in lengthy hospital stays. Extended hospitalizations for monitored parenteral antibiotics for patients with opioid use disorder are challenging for patients, reduce bed capacity, and are associated with significant cost. This observational study reviews the administration of intravenous (IV) antibiotics in a monitored outpatient setting using long-acting injectable buprenorphine (Sublocade, Indivior Inc., North Chesterfield, VA) and a tamper resistant clamp in patients with opioid use disorder . Methods: Long-acting buprenorphine and a tamper resistant clamp were used to treat patients with serious infections and opioid use disorder as outpatients. Results: Hospital days avoided were 30-days per STOP OUD project participant. Eleven of thirteen STOP OUD project participants completed their antibiotic courses as prescribed, there was no evidence of peripherally inserted central catheter (PICC) tampering, and they rated their care as a mean of 4.9/5 (SD 0.4). Institutional savings per STOP OUD patient was $33,000. Outpatient infusion costs were $9,300 for a net savings of $23,700 per STOP OUD project participant. Infections resolved in all participants. Conclusions: The STOP OUD project reduced hospital length of stay for patients with opioid use disorder and serious infections, and had a favorable financial impact.

Warm Autoimmune Hemolytic Anemia as the Initial Presentation of Systemic Lupus Erythematosus (SLE): A Case Report.

BACKGROUND Autoimmune hemolytic anemia is an acquired disorder resulting in the presence of antibodies against red blood cell (RBC) antigens causing hemolysis. Autoimmune hemolytic anemia is of 2 types, Warm antibody mediated and cold agglutinin disease. Warm autoimmune hemolytic anemia (warm agglutinin disease) usually presents with fatigue and other constitutional symptoms and is diagnosed by the presence of IgG antibodies. The disease can occur as idiopathic or secondary to other autoimmune diseases, infections, or even malignancies. The systemic lupus erythematosus (SLE) is an autoimmune disease prevalent in young females. Autoimmune hemolytic anemia can occur as a part of the SLE spectrum however warm autoimmune hemolytic anemia as the initial manifestation of SLE is extremely rare. CASE REPORT Here, we describe a unique case of a 32-year-old woman who presented with vague clinical presentation found to have warm autoimmune hemolytic anemia and further immunological and inflammatory work-up during and after hospitalization lead to the diagnosis of systemic lupus erythematosus. CONCLUSIONS The systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease with unclear etiology affecting multi organs. Variable presentation in addition to the lack of definite pathognomonic features or tests makes the diagnosis of SLE challenging. On the whole autoimmune hemolytic anemia can not only be part of other disease processes but can be an initial presentation, highlighting the importance of thorough work-up in patients presenting with autoimmune hemolytic anemia to aid in timely diagnosis and management of underlying secondary conditions. It is important for providers to be aware of various disease spectrums that contain autoimmune hemolytic anemia for day-to-day clinical practice.

Coronary vasospasm as an etiology of recurrent ventricular fibrillation in the absence of coronary artery disease: a case report.

Background: Vasospastic angina (VA), or Prinzmetal's angina, is characterized by symptoms of coronary angina caused by coronary vasospasm, usually in the absence of atherosclerotic changes. It typically presents with chest pain, which can be accompanied by transient electrocardiographic changes, if visualized during the attack. It can also rarely present with severe manifestations of acute myocardial angina, ventricular fibrillation, or cardiac arrest. Case presentation: We present a case of a 50-year-old Caucasian male who initially presented to the hospital with chest pain and was diagnosed with VA. Later, he was brought to the hospital by emergency medical services later with ventricular fibrillation, despite normal coronary anatomy on angiogram. He was managed with placement of an intra-cardiac defibrillator (ICD) for secondary prevention. The patient continued to have recurrent episodes of ventricular fibrillation with associated ICD shocks, and had multiple admissions to the hospital with similar presentations. Symptoms and arrhythmia improved after optimizing antianginal therapy. Conclusions: Ventricular fibrillation can be an uncommon but severe manifestation during VA crises. In cases with normal coronary vasculature, it is important to recognize VA as a cause of recurrent ventricular fibrillation in order to optimize medical management for prevention of fatal arrhythmias.

Genetic Variation and the Role of Multigene Panel Testing for Hereditary Breast Cancer: A Single-Institution Experience.

Background Breast cancer is the second leading cause of cancer death in women. There are multiple pathogenic mutations in addition to BRCA1/2 that are implicated in causing hereditary breast cancer. Methods and results We conducted a retrospective analysis of 1568 patients with breast cancer diagnosed between January 1, 2015, and December 31, 2018. The age range is 23-87. Among the study population, 26% had genetic testing and 8% of those were found to carry a pathogenic variant, as designated in NCCN (National Comprehensive Cancer Network) Guidelines. Of that 8%, 3.4% were BRCA1 and BRCA2 mutations, and the rest were other prevalent pathogenic variants. Discussion Expanded panel testing has the potential to increase the detection rate of pathogenic variants compared to testing for BRCA1/2 alone. Diagnostic accuracy of genetic causes of breast cancer has a significant clinical impact on patients and their families in terms of targeted treatment and prevention strategies. There is a strong need for further understanding of genetic patterns and variations in hereditary breast cancer. Awareness of the possibility of moderate to low penetrance genes and variants of uncertain significance (VUS) is important to assist with appropriate genetic counseling. We believe that physicians should consider re-testing with an expanded panel if patients previously had BRCA1 and BRCA2 testings only with a negative result as it may identify additional mutations.

The clinical impacts of sleep apnea on mortality and allograft function in kidney transplant patients: A meta-analysis.

BACKGROUND: Sleep apnea (SA) is common in patients with advanced chronic kidney disease. However, its prevalence and clinical significance in kidney transplant patients are unknown. OBJECTIVE: To demonstrate the clinical impacts of SA on kidney allograft and mortality from current evidence to date. MATERIALS AND METHODS: Ovid -MEDLINE, EMBASE, and the Cochrane Library were searched for eligible publications. Kidney transplant recipients aged ≥ 18 years with SA were included. The outcomes included overall mortality, graft failure, and graft loss. Graft loss was attributed by either 1) graft failure requiring renal replacement therapy (RRT)or 2) death. RESULTS: Four observational studies (n = 5,259) were included in the meta-analyses. The mean age was 49.6 ± 0.4 years. Most patients were male (58.3%) and white (82.1%). Up to 25.1% had diabetes, 15.2% had SA, and 36.8% had history of smoking. The mean body mass index was 26.9 ± 0.9 kg/m2. With the mean follow-up duration of 14.4 ± 4.2 years, the pooled adjusted odds ratios (ORs) for graft failure and mortality among kidney transplant patients with SA were 1.061 (95% CI, 0.851 - 1.322; I2 = 41.3%) and 1.044 (95% CI, 0.853 - 1.278; I2 = 0%), respectively. The pooled adjusted OR for graft loss was 0.837 (95% CI, 0.597 - 1.173; I2 = 0%). On subgroup analyses, the ORs for graft failure were similar after adjusted by study year, country, study design, sample size, ethnicity, and sex. No potential publication bias was detected. CONCLUSION: With 14-year follow-up, SA in kidney transplant patients was not associated with worsening clinical and allograft outcomes, such as graft loss, graft failure, and mortality. However, additional observational studies are needed to confirm this finding.

Infectious mononucleosis mimicking Epstein-Barr virus positive diffuse large B-cell lymphoma not otherwise specified.

The Epstein-Barr virus (EBV) causes infectious mononucleosis (IM). In the case of atypical presentation, lymph node and tonsillar biopsies are required to rule out lymphoma. Here, we discuss an 83-year-old male who presented with findings suggestive of diffuse large B-cell lymphoma, which was later ruled out in favor of IM. The distinction between IM and lymphomas is quite challenging due to the extensive overlap between the two diseases. Various studies have demonstrated that EBV-positive diffuse large B-cell lymphoma mimics IM due to large B-cell proliferation in acute EBV infection. We suggest testing for acute EBV infection in addition to utilizing advanced testing to confirm IM in patients with atypical infection, to avoid misdiagnosis leading to inappropriate treatment.

Recurrence of Endometrial Stromal Sarcoma, Two Decades Post-Treatment.

Endometrial stromal cell sarcomas (ESS) are a unique subtype of uterine malignancy. Recurrent low grade endometrial stromal sarcomas (LESS) is identified in half of the patients. Here, we discuss a case of a 76-year-old Asian female with a past medical history of adenomyosis and hypertension who presented to the outpatient clinic with a chief complaint of painless hematuria for one day. Computed tomography scan of abdomen and pelvis with contrast showed a new right-sided mixed cystic and solid pelvic mass measuring up to 6 cm, obstructing and invading the distal right ureter, which was concerning for malignancy. Positron emission tomography (PET scan) demonstrated a right pelvic mass with increased radiotracer activity consistent with malignancy. She underwent laparotomy with excision of the right-sided pelvic mass with an abdominal washout and at the same time, also underwent cystoscopy with right ureteral stent placement. Tissue pathology was consistent with spindle cell neoplasm with staining and histologic features consistent with a recurrent stromal cell sarcoma. Uterine sarcomas tend to have an aggressive nature but there are key features about ESS that distinguish it from other uterine sarcomas. ESS has a more indolent clinical course and can reoccur years after initial diagnosis. They usually relapse locally, although relapses in extra-uterine sites have also been reported. Treatment of ESS depends on the grade and stage at the time of diagnosis. The main line of treatment for ESS consists of a total abdominal hysterectomy (TAH) and salpingo-oophorectomy (BSO). The significance of this case demonstrates that, although remission can be obtained after the initial diagnosis, recurrence can happen. Even when patients seem to be disease-free, clinicians should follow them closely; early diagnosis is important as treatment for this type of entity has a high survival rate.

Triple-Negative Essential Thrombocythemia Complicated by Thrombosis and Acquired von Willebrand Disease in a Young Man.

BACKGROUND Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm (MPN) characterized by sustained thrombocytosis in peripheral blood. Patients typically have gene mutations like JAK2V617F, CALR, and MPLW515L/K. This report describes a young man with ET without any of the above mutations who had paradoxical bleeding due to acquired Von-Willebrand disease. CASE REPORT A young man with a medical history of thrombocytosis on aspirin presented with acute chest pain and was found to have had a myocardial infarction. Emergency cardiac catheterization revealed a thrombotic occlusion of the left anterior descending (LAD) artery and the right posteriolateral system, with an ejection fraction of 25%. He underwent thrombectomy and balloon angioplasty with LAD stenting, and an Impella 2.5 was inserted due to severe left ventricular dysfunction with akinesia. Aspirin and ticagrelor were administered, but the patient later experienced postoperative bleeding from the site of the Impella device. The bleeding was attributed to acquired Von-Willebrand disease secondary to ET. Emergency plateletpheresis was recommended. Further workup demonstrated that he was triple-negative for JAK2, MPL, and CALR gene mutations. CONCLUSIONS The paradoxical bleeding resulting from acquired Von-Willebrand disease was likely an entirely separate entity from the hyper-thrombotic state expected from ET. Careful assessment of clinical symptoms and laboratory markers, in addition to a high degree of suspicion, are needed to diagnose acquired Von-Willebrand disease as a complication of ET.

When Anti-Neutrophil Cytoplasmic Antibody Fails: A Case of Anti-Neutrophil Cytoplasmic Antibody Negative Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a vasculitis of small and medium-sized vessels and presents with varying signs and symptoms. It includes upper and lower airway manifestations and glomerulonephritis with a positive antineutrophil cytoplasmic antibody (ANCA) in serology in 90% of cases. However, about 10% of cases with GPA can have negative serology, often resulting in a diagnostic delay. Obtaining a tissue pathology is needed to confirm GPA. Here we present a 77-year-old male who presented with generalized weakness and loss of appetite and was found to have glomerulonephritis and bilateral opacities in the lungs with a negative ANCA. He was diagnosed with ANCA negative granulomatosis with polyangiitis after a renal biopsy revealed necrotizing inflammation with crescent formation. He was successfully treated with systemic glucocorticoids and rituximab. In conclusion, prompt diagnosis and treatment of ANCA negative vasculitis are required to decrease mortality.

Biosimilars as a Future, Promising Solution for Financial Toxicity: A Review with Emphasis on Bevacizumab.

A biosimilar is a biochemical product like another already approved biologic agent, known as the reference agent. To be endorsed by the Food and Drug Administration (FDA), biosimilars must demonstrate that they are as safe and effective as their reference item, with no clinical distinction. Humanized monoclonal antibodies (mAb) are revolutionizing the treatment of gastrointestinal and gynecologic malignancies. Bevacizumab, trastuzumab, cetuximab, rituximab, and pegfilgrastim are the most widely used mAb products with oncologic indications. Due to the complexities of the regulatory system, it may take time for anti-cancer biosimilars to play a significant game-changing role. Over the last decade, the use of generics has saved billions of dollars every year, and it is expected that biosimilars will soon prove to be a cost-effective alternative and can play an important role in driving down healthcare costs globally. In this review, we provide a critical appraisal of biosimilars with an emphasis on bevacizumab-awwb (Avastin) and its clinico-pharmacologic characteristics, safety, efficacy, interchangeability, regulatory and oncologic perspectives, and overall clinical perception.

Pancytopenia as a Complication of Low-Dose Methotrexate in a Septuagenarian: A Rare Presentation.

Methotrexate (MTX) is an antimetabolite that was initially developed as a chemotherapeutic agent to treat malignancies but later used extensively to treat rheumatological conditions. MTX-induced toxicity is dose- and duration-dependent. Myelosuppression is a rare but fatal complication of MTX that can occur even with low doses used for inflammatory conditions. Multiple factors such as age, renal impairment, and nutritional status increase the risk of developing MTX toxicity. Frequent monitoring of symptoms and lab values are the hallmarks of prompt diagnosis and prevention of complications. Clinicians should have a high degree of suspicion to diagnose pancytopenia secondary to MTX especially in patients with multiple confounding comorbidities. We present the case of a 79-year-old male who presented with mucositis and pancytopenia diagnosed to be secondary to weekly MTX for giant cell arteritis leading to anemia and septic shock causing death.

Drug-Induced Immune Hemolytic Anemia due to Amoxicillin-Clavulanate: A Case Report and Review.

Drug-induced immune hemolytic anemia (DIIHA) is a rare cause of anemia. It is often difficult to distinguish from other causes of hemolytic anemia, thereby delaying diagnosis and treatment. Antibiotics, including penicillins and cephalosporins, are the drugs most often implicated in the development of DIIHA. Discontinuation of the offending agent is often sufficient for treatment. Here, we review the case of a 25-year-old Caucasian female who presented with jaundice and generalized weakness in the setting of outpatient treatment with amoxicillin-clavulanate due to sinus infection. Laboratory testing revealed transaminitis and hemolytic anemia. Direct antiglobulin test (DAT) revealed negative IgG and positive anti-C3. Cold agglutinin titer and Donath-Landsteiner test were negative. The patient was diagnosed with DIIHA most likely due to amoxicillin. She improved with drug cessation and a short course of glucocorticoids. Mechanism of DIIHA, workup, and management are subsequently reviewed.

Opioid antidote induced pulmonary edema and lung injury.

INTRODUCTION: Opioid overdose emergencies are increasing every year, naloxone is the antidote for the treatment of opioid overdose. Naloxone is being dispensed to even lay persons through some programs to prevent opioid overdose deaths. CASE: 23 year old patient presented with naloxone treated opioid overdose complained of chest pain, pink frothy sputum production and shortness of breath. Physical exam showed tachycardia, tachypnea and coarse breath sounds. Imaging of the lungs showed diffuse pulmonary edema. Within an hour after the administration of naloxone patient developed pulmonary edema and lung injury. Patient was managed with non-invasive positive pressure ventilation which improved patient's symptoms in less than 6 hours confirmed by radiological improvement in 24-36 hrs. DISCUSSION: There are no specific observation guidelines post naloxone treatment in opiate overdose patients. We recommend early treatment of naloxone induced pulmonary complications during the observation period with non-invasive positive pressure ventilation to reduce the morbidity.

Stenotrophomonas maltophilia: An Emerging Pathogen of the Respiratory Tract.

BACKGROUND Stenotrophomonas maltophilia has the propensity to cause a plethora of opportunistic infections in humans owing to biofilm formation and antibiotic resistance. It is often seen as a co-organism along with Pseudomonas aeruginosa. CASE REPORT A 70-year-old woman with several co-morbidities presented reporting hypoglycemia and dyspnea. An imaging study of the chest was suggestive of deterioration of pneumonia, with increased opacities. Initial respiratory cultures were negative, while subsequent repeat cultures revealed the growth of Stenotrophomonas maltophilia susceptible to trimethoprim plus sulfamethoxazole and levofloxacin. The patient had a poor prognosis and eventually died despite appropriate measures. CONCLUSIONS A decline in the clinical status of a patient such as ours makes it hard to quickly diagnose this organism correctly. Physicians should thus be cautious of Stenotrophomonas maltophilia-induced infection and more emphasis should be placed on appropriate treatment due to the emerging risk of antibiotic resistance.

Angioimmunoblastic T-cell Lymphoma: An Unusual Case in an Octogenarian.

Angioimmunoblastic T-cell lymphoma (AITL) is an unusual subtype of mature peripheral T-cell lymphoma originating from the follicular T-helper cells and is often associated with autoimmune disorders. AITL is an aggressive lymphoma, presenting with constitutional symptoms, generalized lymphadenopathy, and hepatosplenomegaly. Immunohistochemistry and biopsy are diagnostic methods. The treatment modalities range from steroids, immunomodulators, and cytotoxic chemotherapy. An 87-year-old female presented to the emergency department with cough, dyspnea, dizziness, night sweats, and unintentional weight loss with multiple discrete swellings over her body for a duration of three days. Her physical exam was significant for tachycardia with dry mucous membranes and generalized lymphadenopathy. However, no hepatosplenomegaly was noted. Laboratory investigations revealed neutrophilic leukocytosis (12.8 K/uL), with elevated inflammatory markers (C-reactive protein of 1.39 mg/dL, sedimentation rate of 86 mm/hour). The biopsy of the cervical lymph node revealed atypical lymphoid infiltrates. Flow cytometry showed CD10+ and CD4+/CD8+ T-cells with a minority of CD23+ B-cells, and fluorescence in situ hybridization (FISH) reported gains of the BCL2 gene region on chromosome 18, all of which were suggestive of AITL. She was transferred to an advanced hematology center for staging and targeted therapy. A careful review of the patient with the prompt clinical and histological examination is essential for the correct diagnosis as the differentials are vast due to its non-specific clinical presentation and accurate treatment is a must for complete remission.

Sarcopenia Index Is a Simple Objective Screening Tool for Malnutrition in the Critically Ill.

BACKGROUND: Reliable and valid tools to screen for malnutrition in the intensive care unit (ICU) remain elusive. The sarcopenia index (SI) [(serum creatinine/serum cystatin C) × 100], could be an inexpensive, objective tool to predict malnutrition. We evaluated the SI as a screening tool for malnutrition in the ICU and compared it with the modified-NUTRIC score. MATERIALS AND METHODS: This was a historical cohort study of ICU patients with stable kidney function admitted to Mayo Clinic ICUs between 2008 and 2015. Malnutrition was defined by the Subjective Global Assessment. Diagnostic performance was evaluated with the area under the receiver operating characteristic curve (AUC) and multivariable logistic regression. RESULTS: Of the 398 included patients, 181 (45%) had malnutrition, with 34 (9%) scored as severely malnourished. The SI was significantly lower in malnourished patients than in well-nourished patients (64 ± 27 vs 72 ± 25; P = 0.002), and reductions in SI corresponded to increased malnutrition severity (P = 0.001). As a screening tool, the SI was an indicator of malnutrition risk (AUC 0.61) and performed slightly better than the more complex modified-NUTRIC score (AUC = 0.57). SI cutoffs of 101 and 43 had >90% sensitivity and >90% specificity, respectively, for the prediction of malnutrition. Patients with a low SI (≤43) had a significantly higher risk of mortality (HR = 2.61, 95% CI 1.06-6.48, P = 0.038). CONCLUSION: The frequency of malnutrition was high in this critically ill population, and it was associated with a poor prognosis. The SI could be used to assess nutrition risk in ICU patients.