Impact of genotype on clinical course in sickle cell disease and the utility of neutrophil-lymphocyte ratio: a ten-year single-institution experience.

BACKGROUND: Sickle cell disease (SCD) is a diverse group of blood disorders with significant global disease burden. Contemporary interest in the underlying inflammatory paradigm of SCD has emphasized the role of the neutrophil-lymphocyte ratio (NLR) as a prognostic inflammatory marker. METHODS: We retrospectively reviewed 268 hospitalized patients with SCDs of different genotypes (HbSS, HbSß0 thalassemia, HbSß+ thalassemia, and HbSC), totaling 3329 hospital admissions over a 10-year period. Patients were stratified into SS/Sß0 and Sß+/SC groups for statistical analysis of parameters collected at steady state and at hospital admission. RESULTS: At steady state, per unit increase of hemoglobin values was associated with reduced odds of ≥ 2 hospital admissions per year in SS/Sß0 and Sß+/SC groups; per unit increase in platelet count and white blood cell count was associated with increased odds only in the SS/Sß0 group. The NLR had no association in either group. During admission, a cutoff of NLR = 3.5 discerned infection with a sensitivity of 60% and specificity of 57%. Performance improved when excluding patients on outpatient hydroxyurea therapy (cutoff of NLR = 3.5; sensitivity of 68% and specificity of 64%). CONCLUSION: This study supports the utility of NLR as an accessible adjunctive clinical tool in SCD prognostication.

Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown. MATERIALS AND METHODS: A single-institution retrospective review included patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021. Peri-ampullary tumors were excluded. Levels of CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal Ca 19-9 <35 U/ml; CEA <3 ng/ml). Survival analysis was conducted using Kaplan Meier curves, log-rank test and Cox proportional hazards model. RESULTS: There were 68 patients included in the final analysis. Median age was 67 years old and median follow-up time was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. A concomitant elevation of both tumor markers was associated with worsened OS (HR 2.140, 95% CI: 1.114-4.112; p = 0.019). After controlling for age and sex on multivariate analysis, elevation in both CA 19-9 ≥35 and CEA ≥3.0 remained significantly associated with increased mortality (HR 2.278, 95% CI: 1.162-4.466; p = 0.016). CONCLUSIONS: In summary, CA 19-9 and, to a lesser extent, CEA, show promise as prognostic markers in DA. Larger studies are needed to validate their use and to evaluate their performance as markers of recurrence.

Pericardial Effusion: A Novel Presentation of Aplastic Anemia.

Pericardial effusion is defined as the accumulation of fluid between the visceral and parietal pericardium. The underlying etiology varies as any pathology that causes pericarditis or involves the pericardium can cause effusion. In practice, the majority of pericarditis cases are idiopathic, although these are assumed to be secondary to occult viral infection or inflammatory phenomena. Malignancy, particularly the metastatic spread of noncardiac primary tumors, has been implicated as a differential in the diagnosis of pericardial effusion. Though commonly seen in solid malignancies, effusion has been reported in hematologic malignancies such as myelodysplastic syndrome (MDS), acute leukemia, and lymphoma. Nonetheless, pericardial effusions associated with hematologic conditions are extremely rare with only one case report published describing pericardial effusion secondary to immune thrombocytopenia (ITP). We herein report the first documented case, to our knowledge, of pericardial effusion as an initial clinical manifestation of aplastic anemia in a middle-aged male presenting with pancytopenia.

Recurrent Subclavian Steal Syndrome: A Novel Case of Vasculopathy.

Subclavian steal syndrome (SSS) refers to the phenomenon of retrograde flow in an ipsilateral branch of the subclavian artery due to hemodynamically significant stenosis or occlusion of the ipsilateral proximal subclavian artery. While SSS is usually asymptomatic, it can manifest as vertebrobasilar insufficiency (VBI), ischemia of the affected extremity, or cardiac angina when an internal mammary artery (IMA) is used as a bypass graft. The underlying etiology is most often atherosclerosis but can include Takayasu arteritis, thoracic outlet syndrome, cervical rib, and stenosis secondary to surgical repair of aortic coarctation or tetralogy of Fallot. There are several case reports describing unique presentations of SSS as well as limited reports of double SSS, where the brachiocephalic steno-occlusive disease causes flow reversal in both the ipsilateral vertebral and carotid arteries. We report herein the first documented case, to our knowledge, of a patient with SSS previously treated with left subclavian artery stenting and left common carotid-subclavian bypass who developed recurrent SSS in conjunction with orthostatic cerebral hypoperfusion syndrome (OCHOS) secondary to severe vasculopathy. She presented with recurrent, paroxysmal vertigo and near-syncope associated with left upper extremity paresthesias that would only abate with sitting in the context of left subclavian artery stent restenosis and occlusion of her left common carotid-subclavian bypass graft. Interestingly, her initial presentation entailed retrograde flow from the left vertebral artery to the left subclavian artery, classic for SSS, but recurrence of her SSS involved retrograde flow from the left common carotid artery to the left subclavian artery, a phenomenon which has also not been described in the literature to our knowledge. As her symptoms of VBI appeared to be triggered by standing and not left arm movement, they were considered to be primarily secondary to OCHOS. Consequently, her primary treatment was to increase salt and fluid intake and thus increase intravascular volume for improved cerebral perfusion as she was not deemed to be a suitable candidate for regrafting of the left subclavian artery.

Radiation Treatment for Cancer of the Anal Margin.

OBJECTIVE: To identify best treatment practices by examining outcomes of anal margin cancer patients treated with radiotherapy. METHODS: Relevant literature was compared with 38 patients at our institution treated 1979 to 2019 with curative radiotherapy. Median age was 51. Four patients had T1, 22 had T2, and 12 had T3 disease based on the American Joint Committee on Cancer (AJCC) staging at time of diagnosis. Nodal staging distribution was: N0=33; N1=2; N2=2; N3=1. Median radiation dose was 56 Gy/30 fractions. Five received nodal radiation for node positivity, 29 received elective nodal radiation, and 29 had perineal boost. Twenty-seven received concurrent chemotherapy. RESULTS: Three patients experienced isolated local recurrence, 2 had isolated inguinal node recurrences, and 2 developed distant metastases, 1 of whom also had local and regional recurrence. Ten-year disease-free survival (DFS), cause-specific survival, and overall survival were 87%, 92%, and 68%, respectively. One patient did not complete radiation, and 4 had unexpected treatment breaks. Two received salvage abdominoperineal resections. At last follow-up, 17 were alive with no evidence of disease, 2 were alive with anal margin cancer present, 3 had died with anal margin cancer present at 11, 18, and 21 months from radiation therapy, and 16 had died from intercurrent disease. Median follow-up was 6.6 years (range 0.9 to 29.0 y). Age ≥51 was associated with worse locoregional control ( P =0.018) and DFS ( P =0.0233), males had worse DFS ( P =0.0311), and HIV-positive patients had worse overall survival ( P =0.006). CONCLUSIONS: Radiation provides high locoregional control of anal margin cancer with good long-term outcomes.

A 26-Year-Old Woman With Retinal Telangiectasias, Onychodystrophy, and Persistent Dyspnea.

CASE PRESENTATION: A 26-year-old woman with no significant past medical history sought treatment for worsening dyspnea and hypoxia. The exertional dyspnea began 2 years prior and was associated with substernal chest discomfort. She did not report myalgia, edema, or worsening of dyspnea on supine or upright position. The patient reported no personal history of tobacco or illicit drug use. Family history was unremarkable. She was started on supplemental oxygen at 3 L/min. Initial workup included CT scan angiography of the chest, which showed no pulmonary embolism and normal lung parenchyma. Transthoracic echocardiography showed unremarkable results. She was not given a clear diagnosis for hypoxia and was treated empirically with antibiotics and bronchodilators without improvement. Over the course of 2 years, her condition progressed to requiring 6 L/min nasal canula at rest and associated dyspnea with minimal exertion and a 30-pound unintentional weight loss. During this time, pulmonary function tests noted normal spirometry results and lung volumes, but a decreased diffusing capacity for carbon monoxide of 33%. She also was discovered incidentally to be leukopenic and thrombocytopenic, with subsequent bone marrow biopsy revealing hypocellularity of 30% to 40%. The patient concurrently demonstrated bilateral visual impairment secondary to retinal telangiectasias with increased severity of deficit in the right eye. She subsequently was referred to our institution for further evaluation.