Disseminated Histoplasmosis: A Rare Cause of Pancytopenia in an Immunocompromised Patient.

Histoplasma capsulatum  is a dimorphic fungus endemic to North and South America. This organism's ubiquity outside the traditionally defined region of the Mississippi and Ohio River Valley makes it an important yet often forgotten cause of systemic inflammatory disease. Progressive disseminated histoplasmosis is an uncommon opportunistic infection, largely affecting immunocompromised individuals with defects in T-cell immunity. The initial manifestations of disseminated histoplasmosis present non-specifically with symptoms such as fever, malaise, anorexia, and weight loss. Given this fungi's endemic nature, disseminated histoplasmosis is an essential disease for physicians to diagnose accurately. Diagnosis can be established through antigen detection in the blood or urine, although the gold standard is tissue diagnosis or fungal culture. Treatment of mild to moderate disease consists of an itraconazole regimen for a year, yet severe disease requires an additional 14-day induction therapy with amphotericin B. We present a case of disseminated histoplasmosis in a breast cancer patient, recently treated with neoadjuvant chemotherapy, who presented with new-onset pancytopenia.

The Value of Managing Acute Pancreatitis With Standardized Order Sets to Achieve "Perfect Care".

OBJECTIVES: We aimed to define perfect care index (PCI) metrics and to evaluate whether implementation of standardized order sets would improve outcomes without increasing hospital-based charges in patients with acute pancreatitis (AP). METHODS: This is a retrospective, pre-post, observational study measuring clinical quality, processes of care, and hospital-based charges at a single tertiary care center. The first data set included AP patients from August 2011 to December 2014 (n = 219) before the implementation of a standardized order set (Methodist Acute Pancreatitis Protocol [MAPP]) and AP patients after MAPP implementation from January 2015 to September 2018 (n = 417). The second data set included AP patients (n = 150 in each group) from January 2013 to September 2014 (pre-MAPP) and January 2018 to September 2019 (post-MAPP) to evaluate perfect care between the 2 cohorts after controlling for systemic inflammatory response syndrome at baseline. Length of stay, PCI, and hospital-based charges were measured. RESULTS: The post-MAPP cohort had a significantly shorter length of stay (median, 3 days vs 4 days; P = 0.01). In the second data set, PCI significantly increased after implementation of MAPP order sets (5.3%-35.3%, P < 0.0001). CONCLUSIONS: The MAPP order sets increased the value of care by improving clinical outcomes without increasing hospital-based charges.

Spontaneous pneumothorax secondary to chronic cavitary pulmonary histoplasmosis.

Histoplasma capsulatum is a dimorphic fungus that causes histoplasmosis. Chronic cavitary pulmonary histoplasmosis is rare, and typically manifests as apical cavitary lesions in patients with pre-existing chronic obstructive pulmonary disease. We report a case involving a 60-year-old female who presented to our facility with acute onset of dyspnea and dry cough. Chest x-ray revealed a large left-sided pneumothorax with nearly complete collapse of the left lung. A chest computed tomography scan revealed a left upper lobe cavitary lesion with a bronchopleural fistula. After thoracic surgical bleb resection, a surgical specimen sent for biopsy was positive for Histoplasma capsulatum. The patient's pneumothorax was subsequently diagnosed as chronic cavitary pulmonary histoplasmosis, and itraconazole treatment was initiated. After admission, the patient underwent a thoracotomy with decortication to improve lung expansion; however, the patient's pneumothorax persisted. After a prolonged hospital stay and serial chest x-rays that showed stable residual pneumothorax, the patient was discharged to a long-term acute care facility and itraconazole treatment was continued. Two months after discharge, a repeat chest x-ray showed resolution of her left-sided pneumothorax. This case report highlights the importance of considering pulmonary histoplasmosis (or other endemic pulmonary fungal infections) when a patient presents with apical cavitary lesions.

I can't hear you, you said I had what?: A case report and literature review.

We report the case of a 46-year old African American woman who presented to the emergency department with one week of progressive bilateral deafness associated with worsening gait abnormalities, visual changes, and confusion. She was diagnosed with Wernicke encephalopathy (WE) attributed to alcohol abuse; her symptoms, including hearing loss, improved with thiamine replacement. WE, a condition due to thiamine deficiency, commonly affects those with alcohol use disorder or gastric bypass history. Though traditionally associated with a triad of encephalopathy, ophthalmoplegia, and ataxia, it can be more rarely associated with auditory deficits or other neurologic findings. Though hearing loss has previously been reported as a rare symptom of WE, it has not been described in WE due to alcohol abuse. We performed a review of the literature to determine if WE associated with hearing loss had been previously reported.

Acute Pancreatitis Task Force on Quality: Development of Quality Indicators for Acute Pancreatitis Management.

INTRODUCTION: Detailed recommendations and guidelines for acute pancreatitis (AP) management currently exist. However, quality indicators (QIs) are required to measure performance in health care. The goal of the Acute Pancreatitis Task Force on Quality was to formally develop QIs for the management of patients with known or suspected AP using a modified version of the RAND/UCLA Appropriateness Methodology. METHODS: A multidisciplinary expert panel composed of physicians (gastroenterologists, hospitalists, and surgeons) who are acknowledged leaders in their specialties and who represent geographic and practice setting diversity was convened. A literature review was conducted, and a list of proposed QIs was developed. In 3 rounds, panelists reviewed literature, modified QIs, and rated them on the basis of scientific evidence, bias, interpretability, validity, necessity, and proposed performance targets. RESULTS: Supporting literature and a list of 71 proposed QIs across 10 AP domains (Diagnosis, Etiology, Initial Assessment and Risk Stratification, etc.) were sent to the expert panel to review and independently rate in round 1 (95% of panelists participated). Based on a round 2 face-to-face discussion of QIs (75% participation), 41 QIs were classified as valid. During round 3 (90% participation), panelists rated the 41 valid QIs for necessity and proposed performance thresholds. The final classification determined that 40 QIs were both valid and necessary. DISCUSSION: Hospitals and providers managing patients with known or suspected AP should ensure that patients receive high-quality care and desired outcomes according to current evidence-based best practices. This physician-led initiative formally developed 40 QIs and performance threshold targets for AP management. Validated QIs provide a dependable quantitative framework for health systems to monitor the quality of care provided to patients with known or suspected AP.

A comparison of five methods for extracting DNA from paucicellular clinical samples.

Translational protocols in cancer and carcinogenesis often require isolation of genomic DNA from paucicellular clinical samples. DNA extraction methods for PCR-based applications should optimize the recovery of amplifiable DNA. We compared five methods for DNA extraction in paucicellular epithelial and lymphocyte samples using proportion of extractions producing amplifiable DNA and mean real-time PCR Ct values for GAPDH as the endpoint measures. The methods included solid-phase DNA adsorption (QIAamp), sequential protein and DNA precipitation (Puregene), magnetic bead adsorption (Dynabeads), phenol-chloroform extraction, and single-step proteinase K digestion. In general, the performance of the three commercial kits was superior to either phenol-chloroform extraction or single-step proteinase K digestion. However, QIAamp and Puregene produced amplifiable DNA more frequently than Dynabeads for starting cell numbers <50,000. GAPDH Ct values for QIAamp extractions showed the greatest dynamic range and the best linearity across the range of starting cell numbers, but QIAamp was not statistically significantly superior to Puregene. Of the three commercial kits, Puregene is the least expensive. QIAamp and Puregene DNA extraction methods are well-suited for the preparation of paucicellular clinical samples for PCR-based assays.

Reproducibility of cytologic atypia in repeat nipple duct lavage.

BACKGROUND: It is believed that atypical cells identified by nipple duct lavage (NDL) indicate an increased risk for breast carcinoma similar to atypical ductal hyperplasia diagnosed by tissue biopsy, but many basic performance characteristics of NDL currently are undefined. METHODS: NDL was performed in 108 patients unselected for breast carcinoma risk and then was repeated after 2-14 months (median, 8 months) if the initial lavage was classified as atypical. Breast magnetic resonance images (MRIs) were obtained from a subset of patients who had atypical lavage results. RESULTS: Marked atypia was diagnosed in 22% of 36 breasts with an incident carcinoma compared with 7% of 172 unaffected breasts (P = 0.01). After excluding breasts with an incident carcinoma, there were 32 patients (30%) with either mild or marked atypia. The lavage was repeated in 23 of these women, and the second lavage was classified as atypical in 48%. Neither marked atypia on the initial lavage nor a 5-year Gail risk > or = 1.7% predicted atypia on repeat lavage, but there was a trend for improved reproducibility when the atypia initially was diagnosed in a fluid-producing duct. MRIs were abnormal in 13% of 24 breasts with an atypical lavage, and ductal carcinoma in situ was diagnosed subsequently in 1 breast. CONCLUSIONS: Atypia frequently is diagnosed by NDL, but the reproducibility of repeat lavage is low. Lavage atypia may be physiologic or artifactual rather than pathologic in many instances. Marked atypia occasionally may represent mammographically occult ductal carcinoma in situ.

Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk.

INTRODUCTION: The tumor suppressor genes RASSF1A, APC, H-cadherin, RARbeta2, and cyclin D2 are methylated more frequently in breast cancer than in adjacent benign tissue. However, it is unclear whether promoter methylation of tumor suppressor genes in benign breast tissue is associated with an increased risk for breast cancer. METHODS: Promoter hypermethylation was measured in benign and malignant breast samples obtained by fine needle aspiration biopsy from 27 breast cancer patients and 55 unaffected women whose risk of breast cancer had been defined using the Gail, Claus, and BRCAPRO models. RESULTS: Cyclin D2 methylation occurred in 57% of tumor samples but not in corresponding benign breast samples and in only one sample from an unaffected patient (P < 0.0001). RARbeta2 methylation occurred in 32% of benign breast samples from cancer patients but only 9% of similar samples from unaffected women (P = 0.002). Promoter methylation of RASSF1A and APC occurred more frequently (70% and 56%, respectively) in unaffected women at high-risk for breast cancer as defined by the Gail model than in low/intermediate risk women (29% and 20%, P = 0.04 and P = 0.03). Of the Gail model risk factors, only number of prior breast biopsies was highly correlated with APC and RASSF1A methylation (P = 0.0001 and 0.02, respectively). CONCLUSIONS: Since cyclin D2 promoter methylation occurs almost exclusively in tumors, it may be possible to exploit it for the early detection of breast cancer. Promoter methylation of APC, RARbeta2, and RASSF1A in benign breast epithelium is associated with epidemiologic markers of increased breast cancer risk.

A variant of DNA polymerase beta is not cancer specific.

DNA polymerase beta (pol beta) carries out base-excision repair (BER) required for DNA maintenance, replication, and recombination in eukaryotic cells. A variant characterized by a deletion of exon 11, an 87-bp region in the catalytic domain (pol betadelta208-236), was previously described as a possible cause of genomic instability in cancer. The variant form was hypothesized to act in a dominant negative fashion, due to the fact that the variant inhibits the gap filling and DNA binding activities of the wild-type pol beta protein. DNA polymerase beta transcripts were analyzed in 8 breast cancer cell lines, snap-frozen benign breast tissues from 10 women, and lymphocytes from 10 normal controls, using reverse-transcription polymerase chain reaction (RT-PCR) and three separate primer pairs. The exon 10-12 splice site (variant) was identified using a primer designed to span the spliced exons and by sequencing RT-PCR products that included exon 10, exon 11 (if present), and exon 12. In all of the samples tested, we found both the wild-type and exon 11 87-bp deleted variant mRNAs expressed. We conclude that expression of the DNA polymerase beta variant (pol betadelta208-236) is ubiquitous and not breast cancer specific.

Loss of heterozygosity in benign breast epithelium in relation to breast cancer risk.

The multistage model of breast carcinogenesis suggests that errors in DNA replication and repair generate diversity in the breast epithelium (the mutator phenotype), resulting in selection and expansion of premalignant clones with an acquired survival advantage. We measured loss of heterozygosity (LOH) in breast epithelial cells obtained by random fine-needle aspiration (FNA) biopsy from 30 asymptomatic women whose risk of breast cancer had been defined by the Gail model. Polymorphic microsatellite markers were selected on the basis of their relevance to breast cancer. Breast epithelium of 11 (37%) of 30 women had normal cytology, and that of 19 (63%) had proliferative cytology (eight with atypia and 11 without atypia). LOH was detected in two women with normal cytology and in 14 women (seven with atypia and seven without atypia) with proliferative cytology (P =.007). The frequency of LOH was associated with the cytological diagnosis, as well. The mean proportion (range) of informative markers demonstrating LOH was 0.02 (0-0.20) for the 11 women with normal cytology, as compared with 0.15 (0-0.50) for the 19 women with proliferative cytology (P =.02). Mean lifetime risk for developing breast cancer, as calculated by the Gail model, was 16.7% for women with no LOH compared with 22.9% for women with any LOH (P =.05). These observations support a multistage model of breast carcinogenesis where the initiating events are those that result in genomic instability. Accurate individualized breast cancer risk assessment may be possible based on molecular analysis of breast epithelial cells obtained by random FNA.