Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

Effect of vitamin D and omega-3 on nocturnal enuresis of 7-15-year-old children.

INTRODUCTION: Nocturnal enuresis is known to be a common urinary bladder complication in children. Recent studies have associated vitamin D and omega-3 insufficiency with nocturnal enuresis. AIM: This was a 2-month randomized, placebo-controlled, double-blind trial to measure the effects of vitamin D, omega-3 supplements, and their combination on nocturnal enuresis among 7-15-year-old children. MATERIALS AND METHODS: Participants (180 children with nocturnal enuresis) were selected from children referred to the Pediatric ward of Imam Reza Clinic in Shiraz, Iran. Demographic information and anthropometric measures were taken. Fasting blood and urine samples were also collected, and serum vitamin D and urine prostaglandin E2 were measured before and after intervention. Enuretic children were randomly assigned to four groups: Group A, vitamin D (1000 IU/day); Group B, omega-3 (1000 mg/day); Group C, both omega-3 (1000 mg/day) and vitamin D (1000 IU/day); and Group D, placebo. RESULTS: The results suggested that the study groups were not significantly different regarding demographic and anthropometric measures at baseline. Comparison of different groups revealed that 44.4% of participants in Group A, 28.2% of Group B and 45% of Group C were cured from enuresis (P = 0.03). Serum 25(OH) D was significantly increased in Group A, but urine prostaglandin E2 was not significantly decreased in response to supplementation. Although supplementation with both Group A and Group B were found to be effective, the combined intervention did not increase the effect of each intervention solely. CONCLUSIONS: The results showed that supplementation with vitamin D and omega-3 could reduce the number of wet nights among 7-15-year-old children with nocturnal enuresis.

Over-the-counter use of oral contraceptives in Kuwait.

Oral contraceptive pills (OCPs) are available over-the-counter (OTC) in Kuwait, and constitute a leading method for spacing and limiting children. Data from a nationally representative survey of Kuwaiti women are used to examine OTC use of OCPs. One-fourth of the women initiated use without consulting a doctor, and 50% bought OCPs from the pharmacy. No socioeconomic or demographic differences were found between those who consulted a physician, implying that women of different background have similar accessibility to the physician. Using multivariate analysis, the odds of consulting a physician were found to be significantly lower for women who first bought OCPs directly from the commercial pharmacy. The duration of first time OCP use did not differ according to physician consultation. It is concluded that OTC availability of OCPs has many advantages and prevents unwanted pregnancy. However, there is a need for better packaging and instructions that would enable high-risk women to identify themselves and to use OCPs under physician supervision.

Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice.

BACKGROUND: Pathologic interpretation of biopsy specimens of columnar lined esophagus guides subsequent endoscopic surveillance and/or surgical intervention. The aim of this study was to evaluate pathologic interpretation of columnar lined esophagus by general pathologists in community practice. METHODS: Five histologic slides representing different types of columnar lined esophagus were submitted for review by 20 randomly selected general pathologists in community practice. There were three cases with intestinal metaplasia (one with no dysplasia, one with low-grade dysplasia, and one with high-grade dysplasia) and two cases of gastric metaplasia (one fundic-type and one cardia-type). RESULTS: High-grade dysplasia was identified as such by 30% of pathologists and was called invasive adenocarcinoma by 20%, low-grade dysplasia by 30%, and moderate dysplasia by the remaining 20%. Low-grade dysplasia was identified as such by 35% of pathologists and was called high-grade dysplasia by 20%, moderate dysplasia by 20%, and no dysplasia by 25%. Specialized columnar epithelium with no dysplasia was identified as such by 35%, called low-grade dysplasia by 35%, moderate dysplasia by 15%, indeterminate for dysplasia by 10%, and invasive adenocarcinoma by 5%. Gastric metaplasia without specialized columnar epithelium was identified as Barrett's esophagus in 38% of cases. CONCLUSIONS: Pathologic interpretation of columnar lined esophagus by community pathologists may be subject to marked interobserver variation. The term Barrett's esophagus is often used to describe columnar lined esophagus without goblet cells. Because this finding is not clearly associated with an increased risk of cancer, these data support recent suggestions that the term Barrett's esophagus be abandoned. Interpretations of both high-grade and low-grade dysplasia should be considered for review by experts in esophageal pathology.

Z-stent for malignant esophageal obstruction.

The Z-stent was one of the first self-expanding metal prostheses used for palliation of malignant esophageal obstruction and respiratory esophageal fistula. Its placement has proved to be effective and relatively safe. This article reviews the evolution of the Z-stent; its multiple designs, placement technique, efficacy, complications, and assets and limitations.

Failure of colonoscopy to detect colorectal cancer: evaluation of 47 cases in 20 hospitals.

BACKGROUND: Colonoscopy is the gold standard for the detection of colon polyps and cancers, but failed detections can occur and the reasons are incompletely understood. METHODS: During a retrospective evaluation of the sensitivity of barium enema and colonoscopy in 20 Indiana Hospitals, we encountered 47 cases of colorectal cancer in which a colonoscopy performed within 3 years of the diagnosis had not detected the cancer. Cases were reviewed for location of tumor, extenuating factors, pathologic features, delay in diagnosis from failed detection, and who performed the examination. RESULTS: Failed detection was more likely when colonoscopy was performed by a nongastroenterologist than a gastroenterologist (odds ratio 5:36, 95% CI [2.94,9.77]). Twenty-seven cancers were "missed," and 20 were estimated to be not reached. However, the location of missed tumors and a general absence of adequate documentation of cecal intubation suggested that some cecal and ascending colon cancers recorded as missed may actually have been not reached. Variation in sensitivity among gastroenterologists suggested that meticulous examination is also important in maximizing sensitivity. CONCLUSIONS: These cases suggest several factors that might improve the quality and sensitivity of colonoscopy: (1) examiners should receive adequate training, (2) cecal intubation rates should be high, (3) cecal intubation should be verified by specific landmarks in all cases, (4) failure to reach the cecum should be followed by prompt barium enema, and (5) meticulous examination would appear to improve sensitivity for cancer detection.

Relative sensitivity of colonoscopy and barium enema for detection of colorectal cancer in clinical practice.

BACKGROUND & AIMS: The relative sensitivities of barium enema and colonoscopy for colorectal cancer are still debated. The aim of this study was to determine the relative sensitivity of barium enema and colonoscopy in general clinical practice. METHODS: Medical records of 2193 consecutive colorectal cancer cases identified in 20 central Indiana hospitals were reviewed. All procedures performed within 3 years of the diagnosis were identified. RESULTS: The sensitivity of colonoscopy for colorectal cancer (95%) was greater than that for barium enema (82.9%), with an odds ratio of 3.93 for a missed cancer by barium enema compared with colonoscopy. The sensitivity of double-contrast barium enema (85.2%) was not different from that of single-contrast (81.8%). Barium enema performed no better in the right than the left colon. Cancers detected by colonoscopy were more likely to be Dukes' class A (24.9%) than cancers detected by barium enema (9.8%). Colonoscopy performed by gastroenterologists was more sensitive (97.3%) for cancer than colonoscopy by nongastroenterologists (87%), with an odds ratio of 5.36 for a missed cancer by a nongastroenterologist compared with a gastroenterologist. CONCLUSIONS: Hospital quality assurance committees and/or third-party payors should review the sensitivity of barium enema and colonoscopy by practitioners in their institutions. Corrective measures are recommended when sensitivity deviates significantly below the standard set by gastroenterologists performing colonoscopy in this study.

Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies.

BACKGROUND & AIMS: The miss rate of colonoscopy for neoplasms is poorly understood. The aim of this study was to determine the miss rate of colonoscopy by same day back-to-back colonoscopy. METHODS: Two consecutive same day colonoscopies were performed in 183 patients. The patients were randomized to undergo the second colonoscopy by the same or a different endoscopist and in the same or different position. RESULTS: The overall miss rate for adenomas was 24%, 27% for adenomas < or = 5 mm, 13% for adenomas 6-9 mm, and 6% for adenomas > or = 1 cm. Patients with two or more adenomas at the first examination were more likely than patients with no or one adenoma detected at the first examination to have one or more adenomas at the second examination (odds ratio, 3.3; 95% confidence interval, 1.69-6.46). Right colon adenomas were missed more often (27%) than left colon adenomas (21%), but the difference was not significant. There was evidence of variation in sensitivity between endoscopists, but significant miss rates for small adenomas were found among essentially all endoscopists. CONCLUSIONS: Using current colonoscopic technology, there are significant miss rates for adenomas < 1 cm even with meticulous colonoscopy. Miss rates are low for adenomas > or = 1 cm. The results suggest the need for improvements in colonoscopic technology.

Neoplasia distal to the splenic flexure in patients with proximal colon cancer.

BACKGROUND: Current American Cancer Society recommendations are that persons aged 50 years or older undergo screening flexible sigmoidoscopy every 3 to 5 years. In clinical practice, persons with adenomas at sigmoidoscopy are generally referred for full colonoscopy. However, cancers proximal to the splenic flexure may not be accompanied by neoplasia distal to the splenic flexure. METHODS: In order to estimate how often screening flexible sigmoidoscopy would be negative in persons with proximal cancer, we retrospectively reviewed 2053 consecutive colorectal cancer cases diagnosed from 1988 to 1994. Seven hundred ninety-nine (38.9%) had tumors proximal to the splenic flexure. We selected 358 study cases based on full colonoscopy performed and the colonoscopy reports available. RESULTS: Colonoscopy demonstrated distal adenomas in 77 cases (21.5%): 29 (8.1%) had hyperplastic polyps only, 4 (1.1%) had synchronous cancer, and 248 (69.3%) had no distal polyps. In this population, 77.4% of patients with proximal colon cancer had no distal neoplasia. We estimate that 30% of all patients with colorectal cancer would have a negative screening flexible sigmoidoscopy. CONCLUSIONS: Prospective evaluation of colonoscopic findings in persons with proximal cancers is needed. Ongoing evaluation of colonoscopy as a general screening test is appropriate.