Expert Elicitation Provides a Rapid Alternative to Formal Case-Control Study of an H7N9 Avian Influenza Outbreak in the United States.

An expert elicitation was staged to rapidly decipher plausible routes and risks of pathogen transmission in the 2017 H7N9 avian influenza (AI) outbreak in the four-state region of Tennessee, Alabama, Georgia, and Kentucky. The process included the identification of risk factors found in a preponderance of commercial broiler breeder case farms over matched controls and an opinion-based weighting of risks and mitigations perceived influential to this outbreak. Although the two highly pathogenic AI case farms had general location and company ownership in common, obvious connections were lacking for the remainder of H7N9-infected (all low pathogenicity) commercial farms. Expert elicitation of differences between known cases and controls suggested a key role for environmental rather than lateral (business network) pathways in the distribution of low pathogenicity AI across commercial broiler breeder operations. Factors with greatest strength as predictors of disease, whether or not they were causal, included mesopredator or rodent incursions, enclosure defects, and habitat disturbance that might attract wildlife to the farm (e.g., feed spills and vacating of neighboring properties). Business affiliations that may have facilitated farm-to-farm transfer, in contrast, were limited. Biosecurity standards varied across this study group but were no more or less stringent among cases over controls. However, results from a parallel hypothetical scenario staged to address field data gaps suggest that uniformity and consistency in the implementation of biosecurity practices may impact risk of disease introduction. Importantly, this study was conducted within a few weeks and with little disruption to emergency response activities. As such, the approach offers an alternative model for interim field investigation of new or emerging high-consequence diseases with immediate decision support needs.

Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases.

Three men, aged 53 to 77 years, had carcinomas of the urinary bladder characterized by foci with a deceptively benign histological appearance. In two cases, this feature led to a significant delay in establishing the correct diagnosis. The diagnostic difficulty in these cases resulted from the resemblance of foci of infiltrating carcinoma to von Brunn's nests, cystitis glandularis, cystitis cystica, and nephrogenic adenoma, alone or in combination. Features that helped distinguish these foci from benign processes were an irregular distribution, the presence of large numbers of closely packed epithelial aggregates, focal mild to moderate cytologic atypia, and transitions to unequivocal carcinoma. In a third case, the superficial component of a carcinoma closely resembled an inverted papilloma.

Changes seen in lymph nodes draining the sites of large joint prostheses.

We report the histological findings seen in the lymph nodes draining the sites of large joint prostheses. Two patients underwent multiple prosthetic joint replacements. In one patient, the regional lymph nodes were enlarged during the revision of a total hip prosthesis, and a representative lymph node was resected. The other patient had undergone a pelvic lymph node dissection as part of a staging procedure for prostatic carcinoma. By light microscopy, the lymph nodes from both patients showed markedly dilated nodal sinuses filled with macrophages containing abundant eosinophilic, PAS-positive, granular material. Polarization microscopy revealed needle-like particles within the cytoplasm of the macrophages. We believe that the histological appearance of the lymph nodes represents a florid foreign body reaction to fragments of polyester or polyethylene derived from the articulating surfaces of the joint prostheses and transported to the regional lymph nodes via the lymphatic circulation. Sinus histiocytosis seen in the lymph nodes draining the sites of joint prostheses may resemble, and must be distinguished from, other conditions invoking a sinus pattern of lymphadenopathy, as well from benign and malignant diseases that involve the lymph nodes in a pattern mimicking sinus histiocytosis.

Southwestern Internal Medicine Conference: high-dose intravenous gamma globulin therapy: how does it work?

In the past, IgG replacement has been used primarily to treat patients with hypoglobulinemia or agammaglobulinemia. With the availability of preparations of IgG suitable for intravenous use (IVIG), much higher doses may now be given safely. Surprisingly, administration of very high doses of IVIG in several immunologically related diseases have produced improvement not achieved by other means of therapy. The mechanisms by which IVIG causes these diseases to improve vary with the immunopathogenesis of each disease. Provision of antibodies otherwise unavailable to a given patient, IgG-Fc-receptor blockade, modification of complement activation and modulation of the immune response by anti-idiotypic antibodies are discussed as mechanisms of action of IVIG. Because of the expense and relative scarcity of large amounts of purified, pooled normal IgG, this form of therapy should be used only for selected illnesses for which other treatment is ineffective.

Benzylpenicillin migrates irreversibly into human erythrocytes.

Benzylpenicillin, 5.2% 14C-enriched, was incubated with human whole blood. The erythrocyte component was washed and exhaustively dialyzed and found to contain 6.3% of the original radioactivity. None of the penicillin was found to bind to the cell membrane. Dialysis of the cell contents indicated that none of the penicillin binds irreversibly to the proteins within the cell. Infrared examination of the contents of the cell leads to the conclusion that benzylpenicillin (a monovalent anion) enters the erythrocyte and is hydrolyzed to benzylpenicilloic acid (a divalent anion). This structural change prevents the antibiotic from migrating out of the cell.

Sarcomas of the gastrointestinal tract. Separation into favorable and unfavorable prognostic groups by mitotic count.

The authors reviewed the Massachusetts General Hospital experience with primary malignant stromal tumors of the gastrointestinal tract since 1962. Fifty-one of fifty-five lesions were leiomyosarcomas, and the most common anatomic location was the stomach (47%), followed by small intestine (24%), rectum (11%), colon (7%), duodenum (5%), and esophagus (5%). Most patients presented with gastrointestinal bleeding. There were peaks in age incidence in the fourth and sixth decades. All patients underwent surgery initially, and 40 of 55 had resections with "curative intent." Radiation therapy and chemotherapy were employed to a lesser extent, mainly in a palliative setting. The authors found that using number of mitoses per high-power field as the sole determinant of tumor grade yielded two very distinct clinical populations. Patients curatively resected with low-grade lesions had a better than 80% disease-free survival at 8 years, compared with a mean disease-free interval of only 18 months for high-grade lesions. In resectable disease, tumor grade appears to be the single most important prognostic factor. For gastric lesions there was no apparent advantage in extended resections compared with lesser resections encompassing all gross disease. Because of limited numbers of patients, no benefit could be demonstrated for adjuvant radiotherapy.

Conservative surgery and radiation therapy for soft tissue sarcoma of the wrist, hand, ankle, and foot.

Seventy-eight patients with soft tissue sarcoma (STS) arising in the distal extremities--wrist, hand, finger, ankle, foot, and toe--who were treated with conservation surgery and radiation therapy were studied retrospectively with respect to survival, local recurrence, functional limb preservation, complications, and distant metastasis. After a median follow-up of 7.9 years, actuarial 5-year and 10-year survival rates were 80% and 69%, respectively, and disease-free rates were 61% and 51% at the same times. Actuarial local control rates were 80% and 74% at 5 and 10 years, respectively. Fifteen patients (19%) had local recurrence, but 12 of these were salvaged. Ultimately, 53 patients (68%) retained a normal or fairly normal extremity, six (8%) needed amputation for complications, and 13 (17%) needed amputation to control recurrent disease. The functional outcome was significantly better for patients with upper extremity lesions than for those with lower extremity tumors; even for the latter, this treatment strategy was preferable to amputation. The incidence of hematogenous metastases from distal extremity sarcomas depends on the size of the primary tumor. It was concluded that conservation surgery and radiation therapy (XRT) is an acceptable treatment strategy for STS arising in distal extremities; it yielded a high rate of disease control and functional limb preservation.

Benign smooth muscle tumors of the gastrointestinal tract. A 24-year experience.

Between 1963 and 1987, 131 patients with benign gastrointestinal stromal tumors, primarily leiomyomas, were treated at the Massachusetts General Hospital. Eighty per cent of tumors were located in stomach or small intestine. Two thirds of the tumors were discovered in symptomatic patients before operation by a variety of diagnostic studies. A mitotic index (MI) was determined for each tumor, defined as the number of mitoses per 50 high-power microscopic fields. Only gastric and small intestine tumors had MIs more than 2. Tumors were treated by conservative excision in 67% and radical excision in 33%. At a median follow-up of 6 years there were no local recurrences. No patient with a tumor discovered incidentally has recurred. Three symptomatic patients have died of metastatic liver disease. Each patient with recurrence had a tumor with MI of 2 or more, which represents a recurrence rate of 16% in this group. We conclude that symptomatic gastric and small intestine tumors having two or more mitoses per 50 high-power fields carry a significant risk for recurrence, and that routine pathologic assessment of MI may identify a subset of patients who would potentially benefit from close follow-up and consideration for further therapy.

Minitek urea disk test, a sensitive and cost-effective method to screen for Campylobacter pylori in gastric biopsies.

One hundred fifty-five biopsy specimens from the gastric mucosa of 81 patients undergoing routine endoscopy procedures were tested for the presence of Campylobacter pylori by three methods: Gram stain, culture, and modified Minitek, a rapid urea disk test (BBL Microbiology Systems, Cockeysville, Md.). Twenty-nine patients were infected with C. pylori. Sensitivities and specificities of detection were 100 and 94% with the Minitek test and 93 and 100% with Gram stain, respectively. Rapid testing by the urea disk is a simple, cost-effective, and accurate method for detecting the presence of C. pylori in gastric biopsy specimens.

Management of preterm prematurely ruptured membranes: a prospective randomized comparison of observation versus use of steroids and timed delivery.

The use of hydrocortisone and timed delivery was compared to expectant management of pregnancies complicated by preterm prematurely ruptured membranes in a prospective randomized trial of 73 patients. The incidence of maternal and neonatal complications was compared. There was no significant difference in the incidence of respiratory distress syndrome. Steroid-treated mothers had an increased incidence of postpartum febrile morbidity. We conclude that treatment of women with preterm prematurely ruptured membranes with hydrocortisone and timed delivery offers no advantage over expectant management.