Treatment of HER2+ breast cancer: a retrospective of disease prognosis with loss of HER2 amplification on residual disease after neoadjuvant treatment in a community hospital setting.

Neoadjuvant chemotherapy (NAC) with Anti-Human Epidermal Growth Factor Receptor 2 (Anti-HER2) agents increase rates of pathologic complete response (pCR) in stage II-III, HER2+ breast cancer (BC). Several retrospective studies show HER2 amplification discordance from biopsy to post-NAC residual disease (RD). This phenomenon has unclear prognostic significance. This data was obtained from patients with HER2+ BC treated with NAC between 2018-2021 at our institution. Patients with biopsy and surgical specimens at our institution were analyzed. PCR was defined as ypT0/is N0, and HER2 status on RD was evaluated. 2018 HER2 ASCO/CAP definitions were used. In total, 71 patients were identified. 34/71 patients had pCR and were not included in further analysis. 37/71 patients had RD and HER2 was analyzed. 17/37 had HER2 loss and 20/37 remained HER2 positive. Mean follow-up time for HER2 loss was 43 months and 27 months for patients remaining HER2 positive, but neither group met 5-year Overall Survival as follow-up is ongoing. Recurrence Free Survival (RFS) was 35 months for HER2+ and 43 months for HER2 loss (P = 0.007). However, short follow-up time since diagnosis likely contributed to the underrepresentation of the true RFS of both groups. Therefore, at our institution, retained HER2 positivity on RD after NAC was associated with a statistically worse RFS. Although limited by sample size and follow-up time, further prospective investigation into the significance of HER2 discordance on RD assessed by 2018 definitions could clarify true RFS and if next-generation tumor profiling on RD will yield changes in tailored management.

Pembrolizumab induced pericardial tamponade: A case report.

Key Clinical Message: The occurrence of a large pericardial effusion is not a commonly noted adverse event associated with pembrolizumab and our report demonstrates that a rapid development can be diagnosed with close monitoring and triage to acute medical settings. Abstract: Pembrolizumab is an immune checkpoint inhibitor used in various types of cancers. Pericardial tamponade is a rare side effect reported in only very few case reports. Early recognition and therapeutic intervention is vital in all cases. We report a case of a 54-year-old male with Stage 3 lung adenocarcinoma who developed cardiac tamponade secondary to pembrolizumab and subsequently required pericardial window.

COVID-19 vaccine (Ad26.COV2.S), an unlikely culprit of portal vein thrombosis in a middle-aged man.

While vaccination is the single most effective intervention to prevent spread of COVID-19, rare thromboembolic events have been reported following vaccination with COVID-19 vaccines ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2·S (Johnson & Johnson/Janssen). We present here a case of one such patient who received Ad26.COV2-S (recombinant) JanssenCOVID_19 vaccine. A 55-year-old male presented with a two week history of abdominal pain, nausea, vomiting, and distention. He received the Ad26.COV2-S (recombinant) JanssenCOVID_19 vaccine, one month before onset of symptoms. On presentation, lab results revealed hyponatremia, lactic acidosis, and leukocytosis. CT abdomen and pelvis with contrast revealed moderate circumferential bowel wall thickening, prominent mesenteric vessels present, and a portal vein thrombus extending to the superior mesenteric and splenic veins. An extensive hypercoagulable workup was negative. Patient's history revealed he was a frequent airline passenger but was otherwise negative. Additional etiologies were examined before associating the COVID-19 vaccine with thrombosis and the penultimate diagnosis was only reached by exclusion of other causes after initial evaluation and further outpatient follow up.

The Conundrum of "Warfarin Hypersensitivity": Prolonged Partial Thromboplastin Time From Factor IX Propeptide Mutation.

Carboxylation of glutamic acid residues of vitamin K dependent clotting factors (II, VII, IX, and X) is essential to their biological functioning. Binding of these factors to γ-glutamyl carboxylase enzyme for carboxylation reaction is mediated by wild-type propeptide, a small sequence of amino acids that precede the actual polypeptide. Missense mutations at certain residue severely decrease the affinity of mutated propeptide for the enzyme. Such mutations are reported to occur at codon-10 of factor IX propeptide, a clinically silent metabolic event in normal conditions. However in the presence of warfarin, such mutations and resultant decrease affinity of factor IX propeptide for the enzyme that causes severe selective decrease in factor IX activity. This can potentially leads to life-threatening bleeding complications and known as one of the causes of warfarin hypersensitivity. It is imperative to recognize such cases early on to avoid additional warfarin therapy. Recurrent bleeding episodes, subtherapeutic to therapeutic range international normalized ratio values with relatively prolong partial thromboplastin time should raise the suspicion of underlying factor IX propeptide mutations.

Mobile physician reporting of clinically significant events-a novel way to improve handoff communication and supervision of resident on call activities.

OBJECTIVES: Reporting of clinically significant events represents an important mechanism by which patient safety problems may be identified and corrected. However, time pressure and cumbersome report entry procedures have discouraged the full participation of physicians. To improve the process, our internal medicine training program developed an easy-to-use mobile platform that combines the reporting process with patient sign-out. METHODS: Between August 25, 2011, and January 25, 2012, our trainees entered clinically significant events into i-touch/i-phone/i-pad based devices functioning in wireless-synchrony with our desktop application. Events were collected into daily reports that were sent from the handoff system to program leaders and attending physicians to plan for rounds and to correct safety problems. RESULTS: Using the mobile module, residents entered 31 reportable events per month versus the 12 events per month that were reported via desktop during a previous 6-month study period. CONCLUSIONS: Advances in information technology now permit clinically significant events that take place during "off hours" to be identified and reported (via handoff) to next providers and to supervisors via collated reports. This information permits hospital leaders to correct safety issues quickly and effectively, while attending physicians are able to use information gleaned from the reports to optimize rounding plans and to provide additional oversight of trainee on call patient management decisions.

Selective inhibitors of nuclear export (SINE)--a novel class of anti-cancer agents.

Dysregulation of the nucleo-cytoplasmic transport of proteins plays an important role in carcinogenesis. The nuclear export of proteins depends on the activity of transport proteins, exportins. Exportins belong to the karyopherin ß superfamily. Exportin-1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), mediates transport of around 220 proteins. In this review, we summarized the development of a new class of antitumor drugs, collectively known as selective inhibitors of nuclear export (SINE). KPT-330 (selinexor) as an oral agent is showing activities in early clinical trials in both solid tumors and hematological malignancies.

Warfarin use and prevalence of coronary artery calcification assessed by multislice computed tomography.

Warfarin inhibits the synthesis and function of matrix Gla protein, a vitamin K-dependent protein, which is a potent inhibitor of tissue calcification. We had earlier reported the association of warfarin use with valvular calcification in patients with nonvalvular atrial fibrillation. The aim of our present study was to investigate the association of warfarin use with the presence and severity of coronary artery calcification. A total of 233 patients underwent computed tomography scan (CT) at our institution for the assessment of coronary artery calcium score (CACS). Of 233 patients, the mean age was 63 years, 28 patients (12%) were treated with warfarin, and 205 patients (88%) were not on warfarin. Based on their total CACS, the patients were subsequently stratified into 59 with no coronary calcium (CACS = 0), 63 with low CACS (1-100), 49 with moderate CACS (101-400), 33 with severe CACS (410-1000), and 29 with very severe CACS (>1000). The χ test and Student t-test were used for the comparison of categorical and continuous variables, respectively, between warfarin users and nonusers. Using the variables age, gender, race, smoking, hypertension, diabetes, dyslipidemia, glomerular filtration rate, calcium-phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins, stepwise logistic regression analysis did not show any association of coronary calcification with use of warfarin. In our study, warfarin use was not associated with a higher prevalence or severity of CACS assessed by coronary computed tomography.

Interstitial lung disease associated with azacitidine use: a case report.

Azacitidine is a pyrimidine nucleoside analog licensed for treatment of adult patients with myelodysplastic syndrome. Azacitidine acts as an inducer of cell differentiation by causing demethylation and re-expression of genes silenced by hypermethylation. We report a 56-year-old man with myelodysplastic syndrome who developed interstitial lung disease after azacitidine therapy. Open lung biopsy revealed a nonresolving organizing pneumonia pattern and bronchocentric granulomatous pattern suggestive of drug-induced lung injury. Treatment with steroids and discontinuation of azacitidine led to resolution of interstitial lung disease. The Naranjo adverse drug reaction probability scale score indicated that the association between azacitidine and interstitial lung disease was probable. Interstitial lung disease is a serious but uncommon side effect of this relatively safe drug. The mechanism underlying this is still unclear. The patient was subsequently treated with decitabine with no recurrence of interstitial lung disease.

Association of warfarin use with valvular and vascular calcification: a review.

Vitamin K is required for the activity of various biologically active proteins in our body. Apart from clotting factors, vitamin K-dependent proteins include regulatory proteins like protein C, protein S, protein Z, osteocalcin, growth arrest-specific gene 6 protein, and matrix Gla protein. Glutamic acid residues in matrix Gla protein are γ-carboxylated by vitamin K-dependent γ-carboxylase, which enables it to inhibit calcification. Warfarin, being a vitamin K antagonist, inhibits this process, and has been associated with calcification in various animal and human studies. Though no specific guidelines are currently available to prevent or treat this less-recognized side effect, discontinuing warfarin and using an alternative anticoagulant seems to be a reasonable option. Newer anticoagulants such as dabigatran and rivaroxaban offer promise as future therapeutic options in such cases. Drugs including statins, alendronate, osteoprotegerin, and vitamin K are currently under study as therapies to prevent or treat warfarin-associated calcification. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Very late relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation.

Allogeneic stem cell transplantation is considered to be a curative treatment modality in patients with chronic myelogenous leukemia. However patients are at risk for relapse years after transplantation. Currently we present two patients who relapsed 16 and 24 years after allogeneic bone marrow transplantation, respectively. These patients emphasize the need for long term follow-up of such patients.

Treatment of patients with supraventricular tachyarrhythmias in a medical intensive care unit.

Direct-current cardioversion has a higher success rate than does medical therapy in converting supraventricular tachyarrhythmias to sinus rhythm and should be performed immediately in patients with hemodynamic instability. Hemodynamically stable patients with atrial fibrillation or atrial flutter, a rapid ventricular rate and without preexcitation syndrome should be treated with intravenous beta-adrenergic blocking drugs, amiodarone, verapamil, or diltiazem. In hemodynamically unstable patients with supraventricular tachycardia, intravenous adenosine is the drug of choice.