Mixed-methods process evaluation of a respiratory-culture diagnostic stewardship intervention.

OBJECTIVE: To conduct a process evaluation of a respiratory culture diagnostic stewardship intervention. DESIGN: Mixed-methods study. SETTING: Tertiary-care pediatric intensive care unit (PICU). PARTICIPANTS: Critical care, infectious diseases, and pulmonary attending physicians and fellows; PICU nurse practitioners and hospitalist physicians; pediatric residents; and PICU nurses and respiratory therapists. METHODS: This mixed-methods study was conducted concurrently with a diagnostic stewardship intervention to reduce the inappropriate collection of respiratory cultures in mechanically ventilated children. We quantified baseline respiratory culture utilization and indications for ordering using quantitative methods. Semistructured interviews informed by these data and the Consolidated Framework for Implementation Research (CFIR) were then performed, recorded, transcribed, and coded to identify salient themes. Finally, themes identified in these interviews were used to create a cross-sectional survey. RESULTS: The number of cultures collected per day of service varied between attending physicians (range, 2.2-27 cultures per 100 days). In total, 14 interviews were performed, and 87 clinicians completed the survey (response rate, 47%) and 77 nurses or respiratory therapists completed the survey (response rate, 17%). Clinicians varied in their stated practices regarding culture ordering, and these differences both clustered by specialty and were associated with perceived utility of the respiratory culture. Furthermore, group "default" practices, fear, and hierarchy were drivers of culture orders. Barriers to standardization included fear of a missed diagnosis and tension between practice standardization and individual decision making. CONCLUSIONS: We identified significant variation in utilization and perceptions of respiratory cultures as well as several key barriers to implementation of this diagnostic test stewardship intervention.

Using Administrative Billing Codes to Identify Acute Musculoskeletal Infections in Children.

BACKGROUND AND OBJECTIVES: Acute hematogenous musculoskeletal infections (MSKI) are medical emergencies with the potential for life-altering complications in afflicted children. Leveraging administrative data to study pediatric MSKI is difficult as many infections are chronic, nonhematogenous, or occur in children with significant comorbidities. The objective of this study was to validate a case-finding algorithm to accurately identify children hospitalized with acute hematogenous MSKI using administrative billing codes. METHODS: This was a multicenter validation study using the Pediatric Health Information System (PHIS) database. Hospital admissions for MSKI were identified from 6 PHIS hospitals using discharge diagnosis codes. A random subset of admissions underwent manual chart review at each site using predefined criteria to categorize each admission as either "acute hematogenous MSKI" (AH-MSKI) or "not acute hematogenous MSKI." Ten unique coding algorithms were developed using billing data. The sensitivity and specificity of each algorithm to identify AH-MSKI were calculated using chart review categorizations as the reference standard. RESULTS: Of the 492 admissions randomly selected for manual review, 244 (49.6%) were classified as AH-MSKI and 248 (50.4%) as not acute hematogenous MSKI. Individual algorithm performance varied widely (sensitivity 31% to 91%; specificity 52% to 98%). Four algorithms demonstrated potential for future use with receiver operating characteristic area under the curve greater than 80%. CONCLUSIONS: Identifying children with acute hematogenous MSKI based on discharge diagnosis alone is challenging as half have chronic or nonhematogenous infections. We validated several case-finding algorithms using administrative billing codes and detail them here for future use in pediatric MSKI outcomes.

Evaluating Pancreatic and Biliary Neoplasms with Small Biopsy-Based Next Generation Sequencing (NGS): Doing More with Less.

Pancreatic cancer and cholangiocarcinoma are lethal diseases mainly diagnosed at an inoperable stage. As pancreatobiliary surgical specimens are often unavailable for further molecular testing, this review aimed to highlight the diagnostic, prognostic, and therapeutic impact of next-generation sequencing (NGS) performed on distinct small biopsies, including endoscopic ultrasound fine-needle aspirations and biopsies of pancreatic solid and cystic lesions, biliary duct brushings, and also "liquid biopsies" such as the pancreatic juice, bile, and blood. NGS could clarify indeterminate pancreatic lesions or biliary strictures, for instance by identifying TP53 or SMAD4 mutations indicating high-grade dysplasia or cancer. It could also stratify pancreatic cystic lesions, by distinguishing mucinous from non-mucinous cysts and identifying high-risk cysts that should be excised in surgically fit patients, whereas the combination of cytology, elevated cystic CEA levels and NGS could improve the overall diagnostic accuracy. When NGS is performed on the pancreatic juice, it could stratify high-risk patients under surveillance. On the plasma, it could dynamically monitor the disease course and response to therapy. Notably, the circulating tumor DNA (ctDNA) levels have been associated with staging, grading, and survival. Lastly, NGS has shown potential in identifying potentially actionable molecular alterations. In conclusion, NGS applied on small biopsies could carry significant diagnostic, prognostic, and therapeutic value.

The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management.

This review aims to explore, present, and discuss disorders of glucose metabolism implicated in pituitary gland diseases, the appropriate interventions, as well as the therapeutic challenges that may arise. Pituitary pathologies may dysregulate glucose homeostasis, as both the excess and deficiency of various pituitary hormones can affect glucose metabolism. Increased circulating levels of growth hormone, glucocorticoids or prolactin have been shown to mainly provoke hyperglycemic states, while hypopituitarism can be associated with both hyperglycemia and hypoglycemia. Addressing the primary cause of these disorders with the use of surgery, medical treatment or radiotherapy forms the cornerstone of current management strategies. Physicians should bear in mind that some such medications have an unfavorable effect on glucose metabolism too. When unsuccessful, or until the appropriate treatment of the underlying pituitary problem, the addition of established antidiabetic therapies might prove useful. Further studies aiming to discover more accurate and effective drug preparations in combination with optimal lifestyle management models will contribute to achieving a more successful glycemic control in these patients.

Glucose metabolism disorders in patients with adrenal gland disorders: pathophysiology and management.

The aim of this review is to explore and discuss disorders of glucose metabolism that can arise in individuals with adrenal gland disorders, as well as to enumerate the available therapeutic treatments for these while considering their benefits and drawbacks. Hyperfunctioning adrenal glands, as in hypercortisolism, hyperaldosteronism, and malignancy, or hypofunctioning of adrenal glands, as in adrenal insufficiency, can lead to carbohydrate metabolism dysregulation with subsequent glucometabolic repercussions, either hyperglycemia or hypoglycemia. Glycemic disorders further affect patients' quality of life and represent a therapeutic dilemma for physicians. Current management strategies for glycemic dysregulation in individuals with adrenal gland disorders are fighting the underlying causes, as well as utilizing antidiabetic therapies that aid in maintaining euglycemia. Further research focused on discovering drug preparations of greater accuracy and effectiveness tailored to patients with adrenal problems as well as studies investigating optimal lifestyle management models for these individuals will assist towards achieving optimal regulation of glucose metabolism.

EUS-FNA diagnosis of pancreatic serous cystadenoma with the aid of cell blocks and α-inhibin immunochemistry: A case series.

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow-up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine-needle aspiration (EUS-FNA). In this brief report, we describe six EUS-FNA cases from five patients that were reported as "benign, consistent with serous cystadenoma". Samples were hypocellular, composed of loose clusters and single cuboidal, bland-looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α-inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS-FNAs of SCA commonly result in non-diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management.

Evaluation of metastases to the pancreas with fine needle aspiration: A case series from a single centre with review of the literature.

OBJECTIVE: Fine needle aspiration (FNA) is a minimally invasive albeit highly effective modality used to detect solid and cystic pancreatic lesions. This manuscript aims to present our experience in diagnosing metastases to the pancreas and highlight the importance of immunocytochemistry in the diagnostic process. It also aims to provide a brief review of the literature on this topic. METHODS: We retrospectively searched our archives for cases of metastatic deposits to the pancreas diagnosed with FNA over a 5-year period. We also reviewed the literature for such cases. RESULTS: We describe seven cases from our archives that metastasised to the pancreas. Three of them (43%) represented metastatic renal cell carcinoma while the rest four comprised deposits from a lung adenocarcinoma, a colon adenocarcinoma, an adrenal leiomyosarcoma, and a small cell carcinoma of the urinary bladder, respectively. History of primary malignancy was available for all seven patients. All diagnoses were confirmed with the use of immunostains. In our literature review, similar to our case series, renal cell carcinoma was the most common metastasis to the pancreas managed with FNA (around one out of three patients; 35%). Of interest, our endoscopic ultrasound-FNA case of pancreatic metastasis from urinary bladder small cell carcinoma is the first reported. CONCLUSIONS: As metastases to the pancreas are commonly accompanied by diverse prognostic signatures and management strategies compared to primary pancreatic malignancies, their accurate identification is imperative. Pancreatic FNA is a diagnostic modality that can confirm or exclude metastasis to the organ, especially when immunocytochemistry is applied.

Dissecting the presence of malignant squamous cells in pancreatic cytopathology: A case series.

The presence of malignant squamous cells in pancreatic cytopathology is a rare phenomenon that results either from a primary or a metastatic process. Pancreatic adenosquamous carcinoma (PASC) represents the most common variant of pancreatic ductal adenocarcinoma and is associated with a dismal prognosis. Within the period of 2013-2018, the archives of "Hygeia and Mitera Hospital" were searched for pancreatic cytopathology-related diagnoses that included the interpretation of "malignant squamous cells present." All fine needle aspirations (FNAs) of pancreatic lesions, including liver metastases in patients with known pancreatic primaries, were retrieved along with their relevant clinical information. Five pancreatic and two liver FNAs acquired from a total of six patients were reexamined. None of these patients had any documented history of primary squamous malignancy elsewhere. All pancreatic and one of the two liver FNAs showed malignant squamous cells, identified based on either morphology or immunochemistry. The other liver FNA represented a metastatic deposit which comprised of only a glandular component, whereas the associated pancreatic FNA exhibited both squamous and glandular counterparts. Most cases characteristically showed necrosis and keratinization. Of interest, two cases revealed the presence of tumor-associated giant cells. In conclusion, the presence of malignant squamous cells in pancreatic FNAs could mean the presence of PASC, especially when there is no documented history of a primary malignancy and a complete clinical and imaging workup has been performed. Immunochemistry on cell block material could help to confirm squamous differentiation in the absence of overt keratinization.

Insulin resistance and adrenal incidentalomas: A bidirectional relationship.

An adrenal incidentaloma (AI) is an adrenal mass incidentally found via a radiological modality, independent of an endocrinological investigation. In this review, we aimed to investigate the possible reasons behind the increased frequency in AI detection, especially in ageing populations. The pathophysiological effects of insulin resistance (IR), hyperinsulinemia and various anabolic pathways are analyzed. In addition, we review data from studies indicating an increased incidence of adrenal adenomas and carcinomas in patients with type 2 diabetes mellitus (T2DM). The establishment of obesity as a global epidemic, with a higher prevalence in the female than in the male population, coincide with data regarding AIs and the conditions may share a pathophysiological basis. Furthermore, we discuss the bidirectional association of AIs with obesity, insulin resistance and T2DM, especially in patients with autonomous cortisol secretion. Lastly, as per the definition of an AI, we touch upon the evolution of radiological imaging as another possible cause of the rise in prevalence of AIs, especially concerning the greater use and precision of computed tomography (CT).