Impact of Simultaneous Circulating Tumor DNA and Tissue Genotyping in the Workup of Stage IV Lung Adenocarcinoma on Quality of Care in an Academic Community Medical Center.

PURPOSE: In patients with metastatic lung adenocarcinoma, evidence-based first-line treatment decisions require analysis of tumors for genomic alterations (GAs). Optimizing the genotyping paradigm may improve the delivery of precision oncology care. Actionable GAs can be identified by analyzing tumor tissue or circulating tumor DNA using liquid biopsy. Consensus guidelines for when to use liquid biopsy have not been established. We evaluated the routine use of liquid biopsy performed simultaneously with tissue testing in patients with newly diagnosed, stage IV lung adenocarcinoma. METHODS: We performed a retrospective study comparing patients who underwent tissue genotyping alone (standard biopsy group) with patients who had simultaneous liquid and tissue genotyping (combined biopsy group). We examined the time to reach a final diagnosis, the need for repeat biopsies, and diagnostic accuracy. RESULTS: Forty two patients in the combined biopsy group and 78 in the standard biopsy group met the inclusion criteria. The standard group had a mean time to diagnosis of 33.5 days, compared with 20.6 days in the combined group (P < .001 by two-tailed t-test). In the combined group, 14 patients did not have sufficient tissue for molecular analysis (30%); however, in 11 (79%) of these patients, liquid biopsy identified a GA that eliminated the need for a second tissue biopsy. In patients who completed both tests, each test found actionable GAs missed by the other. CONCLUSION: Performing liquid biopsy simultaneously with tissue genotyping is feasible in an academic community medical center. Potential advantages of simultaneous liquid and tissue biopsies include shorter time to obtain a definitive molecular diagnosis, reduced need for a repeat biopsy, and improved detection of actionable mutations, although a sequential strategy that saves costs by beginning with a liquid biopsy may be ideal.

Risk Factors, Clinical Characteristics, and Prognosis of Acute Kidney Injury in Hospitalized COVID-19 Patients: A Retrospective Cohort Study.

Background: Acute kidney injury (AKI) is a serious complication of COVID-19. Methods: Records of hospitalized adult patients with confirmed SARS-CoV-2 infection from 1 March to 31 May 2020 were retrospectively reviewed. Results: Of 283 patients, AKI occurred in 40.6%. From multivariate analyses, the risk factors of AKI in COVID-19 can be divided into: (1) demographics/co-morbidities (male, increasing age, diabetes, chronic kidney disease); (2) other organ involvements (transaminitis, elevated troponin I, ST segment/T wave change on electrocardiography); (3) elevated biomarkers (ferritin, lactate dehydrogenase); (4) possible bacterial co-infection (leukocytosis, elevated procalcitonin); (5) need for advanced oxygen delivery (non-invasive positive pressure ventilation, mechanical ventilation); and (6) other critical features (ICU admission, need for vasopressors, acute respiratory distress syndrome). Most AKIs were due to pre-renal (70.4%) and intrinsic (34.8%) causes. Renal replacement therapy was more common in intrinsic AKI. Both pre-renal (HR 3.2; 95% CI 1.7-5.9) and intrinsic AKI (HR 7.7; 95% CI 3.6-16.3) were associated with higher mortality. Male, stage 3 AKI, higher baseline and peak serum creatinine and blood urea nitrogen were prevalent in intrinsic AKI. Urine analysis and the fractional excretion of sodium and urea were not helpful in distinguishing intrinsic AKI from other causes. Conclusions: AKI is very common in COVID-19 and is associated with higher mortality. Characterization of AKI is warranted due to its diverse nature and clinical outcome.

Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state.

Objective: COVID-19 is a respiratory disease caused by SARS-CoV-2 with the highest burden in the USA. Data on clinical characteristics of patients with COVID-19 in US population are limited. Thus, we aim to determine the clinical characteristics and risk factors for in-hospital mortality from COVID-19. Design: Retrospective observational study. Setting: Single-network hospitals in Pennsylvania state. Participants: Patients with confirmed SARS-CoV-2 infection who were hospitalised from 1 March to 31 May 2020. Primary and secondary outcome measures: Primary outcome was in-hospital mortality. Secondary outcomes were complications, such as acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS). Results: Of 283 patients, 19.4% were non-survivors. The mean age of all patients was 64.1±15.9 years. 56.2% were male and 50.2% were white. Several factors were identified from our adjusted multivariate analyses to be associated with in-hospital mortality: increasing age (per 1-year increment; OR 1.07 (1.045 to 1.105)), hypoxia (oxygen saturation <95%; OR 4.630 (1.934 to 1.111)), opacity/infiltrate on imaging (OR 3.077 (1.276 to 7.407)), leucocytosis (white blood cell >10 109/µL; OR 2.732 (1.412 to 5.263)), ferritin >336 ng/mL (OR 4.016 (1.195 to 13.514)), lactate dehydrogenase >200 U/L (OR 7.752 (1.639 to 37.037)), procalcitonin >0.25 ng/mL (OR 2.404 (1.011 to 5.714)), troponin I >0.03 ng/mL (OR 2.242 (1.080 to 4.673)), need for advanced oxygen support other than simple nasal cannula (OR 4.608-13.889 (2.053 to 31.250)), intensive care unit admission/transfer (OR 13.699 (6.135 to 30.303)), renal replacement therapy (OR 21.277 (5.025 to 90.909)), need for vasopressor (OR 22.222 (9.434 to 52.632)), ARDS (OR 23.810 (10.204 to 55.556)), respiratory acidosis (OR 7.042 (2.915 to 16.949)), and AKI (OR 3.571 (1.715 to 7.407)). When critically ill patients were analysed independently, increasing Sequential Organ Failure Assessment score (OR 1.544 (1.168 to 2.039)), AKI (OR 2.128 (1.111 to 6.667)) and ARDS (OR 6.410 (2.237 to 18.182)) were predictive of in-hospital mortality. Conclusion: We reported the characteristics of ethnically diverse, hospitalised patients with COVID-19 from Pennsylvania state.

A 45-Year-Old Man with Scleroderma Renal Crisis Associated with a History of Systemic Sclerosis Sine Scleroderma.

BACKGROUND The diagnosis of systemic sclerosis sine scleroderma (ssSSc) with renal crisis is difficult because of its unusual presentation and rarity. CASE REPORT A 45-year-old man presented to the Emergency Department with worsening nausea, vomiting, and exertional dyspnea for 3 weeks. Initial examination showed blood pressure 182/108 mmHg without skin thickening or other skin manifestations. Laboratory investigations showed serum creatinine level 21.73 mg/dL and diffuse airspace opacities on chest radiography. He was admitted to the intensive care unit and started on emergent hemodialysis. He was anemic and became gradually hypoxic, requiring supplemental oxygen. Computed tomography of the chest showed bilateral infiltrates. Antinuclear antibodies (ANA) were positive for centromere pattern with titer of 320. Antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were negative. He was started on therapeutic plasmapheresis (TP) and captopril, which resulted in significant improvement of respiratory symptoms. The kidney biopsy revealed thrombotic microangiopathy. Anticentromere, anti-Scl-70, and antiribonucleic acid polymerase III antibodies, drawn after 4 sessions of TP, were not detected. CONCLUSIONS Here we report a rare case of ssSSc with renal crisis in a patient who presented with acute renal failure requiring hemodialysis and suspected pulmonary hemorrhage. Clinical improvement was achieved by TP and angiotensin-converting enzyme inhibitor. The diagnosis of ssSSc was difficult and required an ANA pattern and kidney biopsy.

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.

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.

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.

A Fatal Case of Vancomycin Associated Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome in a Septuagenarian.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially life-threatening multi-system disorder with a mortality rate of up to 10%, due to severe hypersensitivity drug reaction involving the skin and multiple internal organ systems. We emphasize the increasing prevalence of DRESS syndrome secondary to vancomycin use. A 79-year-old woman presented to the hospital with complaints of right upper quadrant pain, intense pruritis, and jaundice of one-week duration. She was on vancomycin and cefepime for six weeks after a wound infection, and both the medicines were withheld a week ago due to the increasing creatinine. She was afebrile with a pulse-94/min, blood pressure-92/46 mm of Hg, and respiratory rate-14/min. She had scleral icterus, diffuse maculopapular rash, generalized edema, right upper quadrant tenderness, and a positive Murphy's sign. Investigations revealed hemoglobin-10.5 gm/dl, white blood cell count-16.0 K/uL, peripheral eosinophil count-1730 K/uL, alkaline phosphatase-2742 U/L, aspartate transaminase-612 U/L, alanine transaminase-674 U/L, total bilirubin-14.2 mg/dl with a direct component of 9.5mg/dl, blood urea nitrogen-64 mg/dl, creatinine-5.01 mg/dl, glomerular filtration rate-8 ml/min and vancomycin trough level-10.8 mcg/ml. Imaging studies were unremarkable. The renal function improved after high dose steroids, N-acetylcysteine and withdrawal of vancomycin, but the progression of liver failure continued. Eventually, she passed away due to multiorgan failure. Vancomycin is a rare drug to cause DRESS syndrome with 31 cases reported to date. Early recognition of this condition can hasten proper treatment and recovery. Further research on the association of vancomycin trough levels and DRESS syndrome needs to be conducted.

Active Hepatitis C Leading to Refractory Thrombotic Thrombocytopenic Purpura - A Dubious Association and The Challenges Faced in Management.

Acquired thrombotic thrombocytopenic purpura is a combination of thrombocytopenia with microangiopathic hemolytic anemia. A 62-year-old female was transferred from an outside hospital for rapidly worsening mental status and severe thrombocytopenia. Laboratory studies were significant for reduced hemoglobin and platelet count along with raised blood urea nitrogen, creatinine, and serum lactate dehydrogenase levels. Peripheral smear showed numerous schistocytes and further testing showed low ADAMTS13 activity, high ADAMTS13 inhibitor, and positive hepatitis C virus antibody with a high hepatitis C virus ribonucleic acid (RNA) load. The patient was diagnosed with acquired thrombotic thrombocytopenic purpura and started on plasma exchange and steroids. Since no response was achieved until day four of treatment, weekly rituximab was initiated. After the initial two doses of rituximab, she showed significant improvement clinically. ADAMTS13 levels returned back to normal. Cyclosporine was added, following which platelet counts were normalized. Cyclosporine was discontinued, plasma exchange and steroids were slowly tapered off. Follow-up visits showed that the patient is off treatment and continues to be in remission and on regular treatment for hepatitis C. Acquired thrombotic thrombocytopenic purpura is a hematological emergency. Our patient remained refractory to standard therapies and required rituximab and immunosuppressive agents like cyclosporine. We describe the association of active hepatitis C with acquired thrombotic thrombocytopenic purpura that was refractory to plasma exchange, high dose steroids and rituximab. As per our knowledge, this is the first case in the literature to describe a possible association between active hepatitis C and acquired thrombotic thrombocytopenic purpura.

Spontaneous Tumor Lysis Syndrome in Diffuse Large B-cell Lymphoma: Early Diagnosis and Management.

Spontaneous tumor lysis syndrome is a rare oncological emergency associated with multiorgan failure. It is characterized by an elevation of uric acid, hyperphosphatemia, hypocalcemia, hyperkalemia and renal failure in the setting of no active chemotherapy as a result of lysis of massive tumor burden. Early recognition of the disease and prompt management would affect morbidity and mortality. We present the case of an 80-year-old Caucasian male with a history of recently diagnosed diffuse large B-cell lymphoma who had worsening fatigue, weakness and decreased appetite for three days. On admission, laboratory investigations were significant for elevated creatinine, uric acid, and phosphorous. He was started on hemodialysis and rasburicase in view of hyperuricemia. Subsequently, chemotherapy was started. He tolerated chemotherapy initially but later developed multiorgan failure. His family then opted for comfort measures and the patient passed away soon after. In conclusion, spontaneous tumor lysis syndrome is a common association with hematological cancers. Prophylaxis with allopurinol and rasburicase is recommended in all patients who are at an increased risk for tumor lysis syndrome.

From the Breast to the Bowel: An Unconventional Metastatic Presentation.

Breast cancer is the most common cancer in women. The common sites of metastasis include the lungs, liver, and, infrequently, the gastrointestinal (GI) tract. A 72-year-old Caucasian female presented to the hospital with nausea and vomiting, diarrhea, intermittent abdominal pain, and unintentional weight loss. She had had a past medical history of bilateral lobular breast carcinoma and severe iron-deficiency anemia treated with iron transfusions. On arrival, the examination was significant for hypotension and pallor. Laboratory investigations revealed abnormal liver enzymes and raised tumor markers Ca-125 and carcinoembryonic antigen. Imaging studies established a diagnosis of distal small bowel obstruction. The surgical intervention showed the presence of a small bowel tumor, the biopsy findings of which were consistent with metastatic breast cancer, with ER and PR positive but HER-2 negative. She was managed with a selective estrogen receptor degrader and CDK4/6 inhibitor and has been in remission since. Metastasis to the small bowel from the breast is a very rare occurrence. Clinicians should thus maintain a modest amount of suspicion when encountering an uncommon GI presentation of primary breast malignancy. We describe the case of metastatic breast cancer with an atypical GI presentation.