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We examined a large dataset of female metastatic breast cancers (MBCs) profiled with comprehensive genomic profiling (CGP) to identify the prevalence and distribution of immunotherapy responsiveness‐associated biomarkers. DNA was extracted from 3831 consecutive MBCs: 1237 (ERpos/HER2neg), 1953 ERneg/HER2amp, and 641 triple‐negative breast cancer (TNBC). CGP was performed using the FoundationOne® or FoundationOne®CDx NGS assay. Tumor mutational burden (TMB) and microsatellite instability (MSI) were determined in a subset of cases. PD‐L1 expression in immunocytes in a subset of cases was determined by immunohistochemistry using the companion diagnostic VENTANA PD‐L1 SP142 Assay. The median age of the cohort was 54 years (range 20–89). Genomic alterations (GAs)/tumor were similar (range: 5.9–7.3). Markers of potential immune checkpoint inhibitor (ICPI) benefit included: CD274 (PD‐L1) amplification (1%–3%), BRAF GA (1%–4%), TMB of ≥10 mutations/Mb (8%–12%), MSI‐high (0.1%–0.4%), PBRM1 GA (1%), and positive PD‐L1 staining of immunocytes ranging from 13% in ERpos/HER2neg and 33% in ERneg/HER2amp to 47% in the TNBC group. Potential markers of ICPI resistance included inactivating STK11 GA (1%–2%) and MDM2 amplification (3%–6%). MTOR pathway targets were common with lowest frequency in TNBC. ERBB2 short variant mutations were most frequent ERpos/HER2neg and absent in TNBC. BRCA1/2 GA were least frequent in ERneg/HER2amp. The demonstrations of clinical benefit of immunotherapy in MBC support the need for development and utilization of biomarkers to guide the use of ICPIs for these patients. In addition to guiding therapy selection, CGP shows potential to identify GA linked to response and resistance to ICPI in MBC. Both our results and published literature suggest that in addition to guiding targeted therapy selection, comprehensive genomic profiling shows potential to identify genomic alterations linked to response and resistance to immune checkpoint inhibitor (ICPI) therapy in metastatic breast cancer (MBC). The demonstration of clinical benefit of immune checkpoint blockade in MBC supports the need for the development of biomarkers used to guide the use of ICPI drugs for these patients.

Background Appropriate Use Criteria (AUC) for echocardiography are a useful tool to deliver quality healthcare. Our quality-based interventional study was designed to assess the trends in appropriate utilization rates for echocardiography in our institution and improve adherence to the AUC criteria for transthoracic echocardiograms (TTE). Methodology A prospective, time series analysis was conducted at the Upstate University Hospital for the months of July 2019 and August 2020. A chart analysis was performed on 620 consecutive inpatients who underwent TTE for the month of July 2019. We assessed the trends of the appropriate ordering of TTEs. We then updated our order form incorporating the 42 most common appropriate indications. A post-intervention chart analysis was performed on all inpatient TTEs ordered for the month of August 2020 (n = 410). The appropriateness of the TTE for the entire group was determined based on the true indication per chart review. The primary outcome was the proportion of appropriate and inappropriate TTEs ordered. Secondary outcomes included assessing for concordance between the indication on the order requisition form and by chart review. A p-value <0.05 was considered significant. Results Using the 2011 AUC for the entire group, 81% of the pre-intervention TTEs and 79.5% of the post-intervention TTEs were appropriate (p = 0.55). There was a statistically significant reduction in the number of discordant TTE orders before and after the intervention (p < 0.01). In addition, we noted increased appropriateness of TTEs in the concordant group both pre and post-intervention. Conclusions Our study demonstrates a significant increase in the concordance between the TTE order sheet and actual indication per chart review with the intervention. This can translate into improved scanning and physician reading quality and time, thereby increasing focus on areas of interest according to the true indication. There was no significant increase in the appropriate TTEs ordered.

Introduction New treatment strategies for advanced non‐small‐cell lung carcinoma (NSCLC) include synthetic lethality targets focused on protein arginine methyl transferases such as PRMT5 that exploit the impact of genomic loss of methylthioadenosine phosphorylase (MTAP). Methods Twenty nine thousand three hundred seventy nine advanced NSCLC cases underwent hybrid‐capture based comprehensive genomic profiling between June 1, 2018 and May 31, 2020. PD‐L1 expression was determined by immunohistochemistry (Dako 22C3 PharmDx assay). Results 13.4% (3928/29,379) NSCLC cases exhibited MTAP loss distributed in adenocarcinoma (59%), squamous cell carcinoma (22%), NSCLC not otherwise specified (16%), and 1% each for large‐cell neuroendocrine, sarcomatoid, and adenosquamous carcinoma. Statistically significant differences in mitogenic driver alterations included more KRAS G12C mutations in MTAP‐intact versus MTAP‐lost (12% vs. 10%, p = 0.0003) and fewer EGFR short variant mutations in MTAP‐intact versus MTAP‐lost NSCLC (10% vs. 13%, p < 0.0001). Statistically significant differences in currently untargetable genomic alterations included higher frequencies of TP53 (70% vs. 63%, p < 0.0001) and RB1 inactivation (10% vs. 2%, p < 0.0001) in MTAP‐intact compared to MTAP‐lost NSCLC. SMARCA4 inactivation (7% vs. 10%, p < 0.0001) was less frequent in MTAP‐intact versus MTAP‐lost NSCLC. Alterations in ERBB2, MET, ALK, ROS1, and NTRK1 did not significantly differ between the two groups. Predictors of immunotherapy efficacy were higher in MTAP‐intact versus MTAP‐lost NSCLC including tumor mutational burden (9.4 vs. 8.6 mut/Mb, p = 0.001) and low (30% vs. 28%, p = 0.01) and high PD‐L1 (32% vs. 30%, p = 0.01) expression. Alterations in biomarkers potentially predictive of immune checkpoint inhibitor resistance (STK11, KEAP1, and MDM2) were similar in the two groups. Conclusions MTAP loss occurs in 13% of NSCLC, supporting the development of targeted therapies to exploit PRMT5 hyper‐dependence. MTAP loss is accompanied by small differences in targeted and immunotherapy options which may impact future combination strategies. MTAP loss occurs in 13% of non‐small‐cell lung cancers, raising the possibility of targeted treatment with synthetic lethality agents such as PRMT5 inhibitors.

Shewanella species are distributed ubiquitously in the soil and water, being common in the marine habitat. Although these bacilli were thought to be rarely pathogenic, there has been an increasing number of reports of them being implicated in a wide variety of clinically significant infections. Three distinct species were initially recognized by MacDonell and Colwell. They were Shewanella putrefaciens, hanedai and benthica. Shewanella algae, which is the most common human clinical isolate, was believed to be a strain of Shewanella putrefaciens by some authors, and was later grouped as a separate and distinct entity. With multi-drug resistance on the rise and the lack of large-scale systemic studies, we describe a case of bacteremia caused by this rare organism. We hope to increase the awareness among care providers on the same.

Background: Lacrimal gland tumors are rare with data limited to very few large studies. Contemporary strategies like orbit sparing surgeries and neoadjuvant intraarterial chemotherapy remain controversial.Methods: This is a retrospective cohort analysis of epithelial lacrimal gland tumors from the 2004-2016 National Cancer Database. Patients were stratified based on the type of surgery (limited vs destructive) and various treatment modalities employed.Results: Squamous cell carcinoma (33.48%) and adenoid cystic carcinoma (29.45%) were the commonest histologies (N=669). Comparison of limited (46.33%) vs destructive procedures (53.11%) among 482 patients did not show any survival difference, nor the comparison between surgery vs ± chemotherapy vs ± radiotherapy among 472 patients.Conclusion: Squamous cell carcinoma and adenoid cystic carcinoma are the commonest types of lacrimal gland tumors seen in our study. Tumor spread from adjacent sites may have contributed to the higher percentage of squamous cell carcinomas seen. The type of surgery or chemoradiation use did not alter survival.

Drug-induced pancreatitis is a rare entity. The diagnostic criteria for drug-induced pancreatitis include the development of pancreatitis during drug therapy, elimination of all other possible causes, resolution with discontinuation of the offending drug, and reappearance on using the same drug. Several drugs have been implicated in having an association with pancreatitis. Tetracyclines are considered to be a Class I medication (medications implicated in greater than 20 reported cases of acute pancreatitis). However, there are very few reported cases of doxycycline-induced acute pancreatitis. We report the case of a 55-year old male who presented to the emergency department (ED) with three days of progressively severe and constant mid-epigastric abdominal pain. On evaluation, he was found to have elevated lipase levels. Computed tomography (CT) scan of his abdomen revealed findings consistent with pancreatitis without any evidence of gallstones or common bile duct dilation. He denied alcohol use, trauma, and insect bites or stings. His calcium and triglyceride levels were within normal limits. His blood cultures did not show any bacterial growth. He had recently been initiated on doxycycline for concerns of cellulitis and had begun to develop abdominal pain seven days after the initiation of doxycycline. He had completed his antibiotic course on the day of presentation to the ED. He had no other recent medication changes. He had subsequent improvement of symptoms off of the doxycycline and with supportive care. Given that all other causes of pancreatitis had been excluded and that he had been initiated on doxycycline prior to presentation, the etiology was attributed to being likely secondary to doxycycline use. Our case highlights the importance of reviewing outpatient medications by the hospital medicine team and awareness of rare triggers for acute pancreatitis.

In the pre-antibiotic era, neurosyphilis (NS) was common, occurring in 34% of patients with syphilis. Currently, there has been a rising trend in syphilis with HIV-infected patients being more prone to develop NS. Ocular involvement is very rare in NS and accounts for only 1%-5% of the cases in the United States. We report the case of a 53-year-old male with a past medical history of gastroesophageal reflux disease and hyperlipidemia who presented to his ophthalmologist for blurred vision in both eyes. He had been noticing a black spot in the visual field of his left eye for two weeks. He had also noticed a rash on his forearms. His past and social history was significant for treated Lyme disease, having pet cats. He identified as a heterosexual male, married, and with five children. However, on further history taking, he reported a homosexual exposure about five years prior. He denied any history of genital ulcer or penile discharge. On examination at the ophthalmology clinic, he was found to have a visual acuity of 20/20 right eye and 20/100 left eye. Posterior segment examination of the both eyes showed subtle neuritis and vasculitis. Fundus photography revealed subtle neuroretinitis bilaterally. Work up was initiated for inflammatory and infectious causes. His rapid plasma reagin and fluorescent treponemal antibody absorption showed positive titers for syphilis. His presentation was most consistent with ocular syphilis. A lumbar puncture (LP) was done with Venereal Disease Research Laboratory (VDRL) positivity in the spinal fluid. He was therefore initiated on intravenous (IV) penicillin four million units every four hours for 14 days. His ophthalmology follow-up after one month showed both subjective and objective improvement in his visual symptoms. He also followed with the infectious disease team and a repeat LP done three months later showed nonreactive VDRL in cerebrospinal fluid (CSF). Ocular syphilis is increasing in incidence. Clinical presentation is variable, and a high index of suspicion with a low threshold for serological testing are important as early treatment can reverse retinal changes and restore visual acuity. There is a recommendation for CSF examination in all patients with ocular syphilis including HIV-negative cases. There have been studies showing a high CSF abnormal rate in HIV-negative patients with ocular syphilis. The recommended treatment for NS is aqueous crystalline penicillin G (18 to 24 million units per day, administered as three to four million units IV every four hours, or 24 million units daily as a continuous infusion) for 10 to 14 days. Follow-up is a key component of management with neurological examination and LP for CSF VDRL performed three months after treatment and every six months after, until the CSF is nonreactive for VDRL with normal white blood cell count. It is important to be cognizant of the rising trend of ocular syphilis, even in HIV-negative individuals. Early treatment is time sensitive to preventing permanent vision loss. Our case also emphasizes on thorough history taking, even for patients who appear to be at a low risk for sexually transmitted infections.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive malignancy with poor outcomes. Although novel options like tagraxofusp, a CD123-directed cytotoxin, has emerged and is promising, treatment options are very limited in the relapsed and recurrent setting. We present a case of refractory BPDCN in a 62-year-old man who showed a complete bone marrow response to liposomal daunorubicin and cytarabine (vyxeos).

Therapeutic plasma exchange (TPE) is a procedure for removal of plasma and its components while leaving behind cellular elements via an apheresis device. It is used in multiple conditions one among which is systemic lupus erythematosus (SLE). Adverse reactions from TPE range from mild hypotension and fever to life-threatening cardiovascular compromise. We report the case of sudden hemodynamic collapse following TPE for a neuropsychiatric lupus flare in a patient on losartan. A 62-year-old Caucasian female with a history of drug-induced lupus presented to the hospital with symptoms of a neuropsychiatric lupus flare. She was initiated on TPE with 5% albumin based on recommendations by her rheumatologist. Shortly after TPE, she became hypotensive with poor response to fluid boluses, requiring pressor support and intubation. These symptoms resolved within 24 hours on supportive measures. This was believed to be due to losartan use on the day of TPE. The medication was discontinued and she had further sessions of TPE with no complications. Angiotensin-converting enzyme (ACE) inhibitors have previously been associated with flushing and hypotension in patients undergoing TPE. Patients undergoing TPE have an activation of the prekallikrein and bradykinin system on contact with the extracorporeal membranes. ACE inhibitors potentiate this reaction by inhibiting bradykinin catabolism. Angiotensin receptor blockers (ARBs) have also been postulated to cause elevated bradykinin levels although data pertaining to the use of ARBs in TPE is limited. We hope to highlight this rare interaction in our case and emphasize the need for further data with regard to the same.

Perivascular epithelioid cell tumors (PEComas) are related to the tuberous sclerosis complex (TSC) and are commonly benign. When malignant, they can be aggressive with local invasion and metastatic spread. Conventional PEComas do not have TFE3 gene rearrangement and are associated with TSC with a preference for an occurrence at a younger age. We report a case of a young male who had progressive chronic hip pain and was found to have a TFE3-associated PEComa in his pelvic region.