Mutant PPM1D- and TP53-Driven Hematopoiesis Populates the Hematopoietic Compartment in Response to Peptide Receptor Radionuclide Therapy.

PURPOSE: Hematologic toxic effects of peptide receptor radionuclide therapy (PRRT) can be permanent. Patients with underlying clonal hematopoiesis (CH) may be more inclined to develop hematologic toxicity after PRRT. However, this association remains understudied. MATERIALS AND METHODS: We evaluated pre- and post-PRRT blood samples of patients with neuroendocrine tumors. After initial screening, 13 cases of interest were selected. Serial blood samples were obtained on 4 of 13 patients. Genomic DNA was analyzed using a 100-gene panel. A variant allele frequency cutoff of 1% was used to call CH. RESULT: Sixty-two percent of patients had CH at baseline. Persistent cytopenias were noted in 64% (7 of 11) of the patients. Serial sample analysis demonstrated that PRRT exposure resulted in clonal expansion of mutant DNA damage response genes (TP53, CHEK2, and PPM1D) and accompanying cytopenias in 75% (3 of 4) of the patients. One patient who had a normal baseline hemogram and developed persistent cytopenias after PRRT exposure showed expansion of mutant PPM1D (variant allele frequency increased to 20% after exposure from < 1% at baseline). In the other two patients, expansion of mutant TP53, CHEK2, and PPM1D clones was also noted along with cytopenia development. CONCLUSION: The shifts in hematopoietic clonal dynamics in our study were accompanied by emergence and persistence of cytopenias. These cytopenias likely represent premalignant state, as PPM1D-, CHEK2-, and TP53-mutant clones by themselves carry a high risk for transformation to therapy-related myeloid neoplasms. Future studies should consider CH screening and longitudinal monitoring as a key risk mitigation strategy for patients with neuroendocrine tumors receiving PRRT.

"Tear Drops in the Duodenum": Uncommon Cause of Iron Deficiency Anemia in Adults.

A 64-year-old man presented to the internal medicine resident clinic with fatigue and abdominal pain of six-month duration. He did not have diarrhea, hematemesis, melena, or hematochezia. Physical examination was unremarkable. Laboratory findings were consistent with iron deficiency anemia. Upper and lower gastrointestinal (GI) endoscopies revealed normal findings. Duodenal biopsy showed trophozoites (tear-drop-shaped) morphologically consistent with Giardia duodenalis. He was prescribed metronidazole and iron replacement therapy, with a resultant improvement in symptoms as well as lab values at the four-month follow-up visit.

Immunization Against Hepatitis A Virus and Hepatitis B Virus in Patients with Chronic Liver Disease: Are We Doing a Good Job?

INTRODUCTION: In the era of highly effective vaccines for Hepatitis A Virus (HAV) and Hepatitis B Virus (HBV), acute viral hepatitis in patients with a chronic liver disease remains a public health concern. Vaccination for HAV and HBV is endorsed by all liver society guidelines. The aim of our study was to determine the rates of immunization in an internal medicine resident clinic. METHODS: We identified patients with a chronic liver disease seen at the University of Oklahoma Internal Medicine resident clinic between June 2014 and May 2015. ICD-9 code 571 was used to identify patients with a chronic liver disease. Vaccination records and patient data were reviewed. RESULTS: A total of 141 patients with a chronic liver disease (mean age 54.1 years, 56% males) were identified. Almost half of the patients (47.5%) were also being seen in the gastroenterology clinic. During the internal medicine resident clinic visit, vaccination against HAV and HBV was addressed for 50% and 46% of the patients, respectively. Patients being seen by senior residents were more likely to be immunized against HAV (OR 2.7, p=0.009) and HBV (OR 2.1, p=0.03). Patients followed in the GI clinic were more likely to be immunized against HAV (OR 2.1, p= 0.02) and HBV (OR 2.0, p=0.02). The gender of the treating physician and etiology had no impact on vaccination rates. DISCUSSION: Immunization rates for HAV and HBV remain subpar despite clear guidelines for patients with a chronic liver disease. This provides an important avenue for improvement. Different strategies, including resident education, developing vaccination protocols, and referral to the gastroenterology clinic, are likely to improve vaccination status for patients with chronic liver diseases.

Chilaiditi's Sign Associated with Acute Colonic Pseudo-obstruction: A Radiological Diagnosis.

Chilaiditi's sign is a rare radiological anomaly of hepato-diaphragmatic interposition of the bowel. We report a case of Chilaiditi's sign associated with acute colonic pseudo-obstruction. A 90-year-old male was admitted for hypertensive emergency. His physical examination showed a distended abdomen, decreased bowel sounds, and right upper quadrant tenderness. A chest radiograph demonstrated marked elevation of the right diaphragm and interposition of the hepatic flexure of the colon between the diaphragm and the liver, along with marked gaseous distension up to 9 cm in the ascending colon without any small bowel distension. The patient was managed conservatively with bowel rest, stool softeners, enemas, and intravenous (IV) hydration. The patient improved clinically with resolution of colonic distension. Chilaiditi's sign and Chilaiditi syndrome are rare entities and therefore are often misdiagnosed and mismanaged. Awareness of the radiological sign, the syndrome itself, and the association with acute colonic pseudo-obstruction is important for all care providers so that they can opt for more conservative management strategies instead of unnecessary interventions including surgeries.