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γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but they also constitute a major lymphocyte population infiltrating colorectal cancers (CRCs); however, their temporal contribution to CRC development or progression remains unclear. Using human CRC samples and murine CRC models, we found that most γδ T cells in premalignant or nontumor colons exhibit cytotoxic markers, whereas tumor-infiltrating γδ T cells express a protumorigenic profile. These contrasting T cell profiles were associated with distinct T cell receptor (TCR)-Vγδ gene usage in both humans and mice. Longitudinal intersectional genetics and antibody-dependent strategies targeting murine γδ T cells enriched in the epithelium at steady state led to heightened tumor development, whereas targeting γδ subsets that accumulate during CRC resulted in reduced tumor growth. Our results uncover temporal pro- and antitumor roles for γδ T cell subsets.

Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection 1,2 , but the host response at the lung tissue level is poorly understood. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19. The lungs from individuals with COVID-19 were highly inflamed, with dense infiltration of aberrantly activated monocyte-derived macrophages and alveolar macrophages, but had impaired T cell responses. Monocyte/macrophage-derived interleukin-1β and epithelial cell-derived interleukin-6 were unique features of SARS-CoV-2 infection compared to other viral and bacterial causes of pneumonia. Alveolar type 2 cells adopted an inflammation-associated transient progenitor cell state and failed to undergo full transition into alveolar type 1 cells, resulting in impaired lung regeneration. Furthermore, we identified expansion of recently described CTHRC1 + pathological fibroblasts 3 contributing to rapidly ensuing pulmonary fibrosis in COVID-19. Inference of protein activity and ligand-receptor interactions identified putative drug targets to disrupt deleterious circuits. This atlas enables the dissection of lethal COVID-19, may inform our understanding of long-term complications of COVID-19 survivors, and provides an important resource for therapeutic development.

Many of the causes of complaints can be reduced but not completely eliminated. Appropriate attention through education and quality management keeps the department's attention focused on increasing patient satisfaction.

Young, febrile children are at risk for occult bacteremia. However, some positive blood cultures are contaminants. This study assesses the ability of preliminary blood culture results to distinguish between pathogens and contaminants. Positive blood cultures were obtained and evaluated from 210 otherwise well febrile children, at risk for occult bacteremia, three months to three years of age, who were without invasive bacterial disease. These children had entered a pediatric emergency department between 1983 and 1989 and were not admitted to the hospital. Blood cultures of true pathogens became positive more rapidly than contaminants, 13.8 +/- 7.0 hours versus 37.6 +/- 29.9 hours, respectively (P < 0.0001). Gram stain results were used as a diagnostic test for pathogenicity with a sensitivity of 98.1% and specificity of 54.5% for the entire population, and 100% and 77.3% respectively, for those cultures becoming positive after 24 hours. Time to positivity and initial gram stain results are valuable diagnostic tests in distinguishing between pathogens and contaminants for blood cultures obtained from children at risk for occult bacteremia.

Short-course therapy for pediatric urinary tract infection (UTI) remains controversial. The present study was undertaken to compare the effectiveness of cefuroxime axetil (Ceftin) as short-course (2-day) versus conventional (10-day) therapy for uncomplicated pediatric UTIs. In a randomized, controlled, prospective study, we enrolled 50 children, 2-11 years of age, to receive oral cefuroxime axetil, 125 mg twice a day, for either 2 or 10 days. UTI was defined as at least 10(5) colonies/ml of a single pathogen isolated on clean catch, or at least 10(4) colonies/ml on a catheterized specimen. A 10-fold or greater reduction in colony count of the initially isolated organism (3-5) days after stopping therapy was considered a bacteriologic success, as long as the absolute colony count was below the threshold for UTI described above. Patients were followed for 15 months with multiple repeat urine cultures and radiologic studies. Twenty-five of the 50 patients enrolled were withdrawn, including 12 for initially inadequate colony counts. Eight of 12 patients in the short-course group (67%), versus 12 of 14 in the conventional-therapy group (86%), were initial bacteriological successes, a nonsignificant difference. All 37 initially isolated uropathogens were sensitive to cefuroxime axetil in vitro. Cefuroxime axetil is an effective antimicrobial for uncomplicated pediatric UTIs. Two-day therapy with cefuroxime axetil appears to be as effective as 10-day therapy, although sample size was limited in this study.

Acute infectious epiglottitis in children is a well-recognized clinical entity. We report the development of acute thermal epiglottitis after ingestion of hot tea by a three-year-old patient. Clinical and radiographic findings in our patient and others reported in the literature resemble acute infectious epiglottitis. In all cases of burns around the mouth, the possibility of intraoral and respiratory damage must be considered. Because of the high risk of upper airway obstruction, children in whom thermal epiglottitis is suspected should be observed in the intensive care unit and have appropriate airway management.

The diagnosis of bacterial meningitis depends on a lumbar puncture (LP). Sometimes, antibiotics are administered before a LP that is delayed owing to prior need for computerized tomography (CT) scan, technical problems, inability to obtain consent, or an unstable patient. We examined the accuracy of blood culture, cerebrospinal fluid (CSF) Gram's stain, and antigen detection by latex for organism identification of meningitis. All patients admitted to the Children's Hospital of Buffalo between January 1, 1984 and December 31, 1989 and having a CSF culture diagnosis of bacterial meningitis had their charts retrospectively reviewed. Patients excluded from the study were those with neural tube defects or CSF catheters, those admitted directly to the Intensive Care Nursery (ICN), those whose positive CSF cultures were determined to be a contaminant, those whose medical records were not found, or those older than 16 years. We analyzed a total of 178 patients with positive CSF cultures and the confirmed diagnosis of bacterial meningitis. Of 169 patients who had a blood culture performed, 86% had the organism responsible for meningitis recovered by this test, with the highest yield of 91% occurring in the 2.5-month to 24-month age group. Blood culture identified the bacteria in 94% of those patients with Haemophilus influenzae meningitis, and this yield increased to 100% when patients who had been pretreated with antibiotics were excluded. The combination of blood culture, CSF Gram's stain, and/or latex agglutination identified the causative bacteria in 92% of patients with meningitis. Blood culture, CSF Gram's stain, and latex agglutination are useful in identifying the organism causing pediatric meningitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Children suffering physical abuse are at risk for abdominal trauma. When the abdominal trauma is not evident clinically and remains occult, the child's condition can rapidly deteriorate before the diagnosis is made, and delay may occur in the activation of child protective services. The use of markers for abdominal trauma in the evaluation of cases of child physical abuse was examined. Children younger than 12 years presenting to the Emergency Department at the Children's Hospital of Buffalo from August 1989 through April 1990 for the evaluation of suspected physical abuse were prospectively entered in the project. All patients had a complete history and physical examination performed. Those patients who did not show any signs of abdominal injury had the following laboratory tests done: (1) levels of liver transaminases, lactate dehydrogenase, and alkaline phosphatase; (2) amylase level; and (3) uranlysis. Of 49 patients without clinical signs of abdominal trauma, 4 children had elevated transaminase levels. Three of these 4 patients had liver lacerations documented by subsequent abdominal computed tomographic scans. A new finding of transaminase levels as markers of occult liver injury in children suffering physical abuse is reported.

Study Objectives: To determine the effect of syrup of ipecac (SOI) on time to receive and retention of activated charcoal (AC) and on total ED time., Design: During a two-year period, patients were enrolled in a prospective, randomized, unblinded, controlled trial., Setting: All patients were recruited and studied in a pediatric emergency department., Participants: Seventy children less than 6 years old (mean age, 2.4 +/- 0.2 years) who presented with mild-to-moderate acute oral ingestions., Interventions: Group 1 received SOI before AC. Group 2 received only AC., Measurements and Main Results: Group 1 patients took significantly longer to receive AC than group 2 from the time of ED arrival (2.6 +/- 0.1 vs 0.9 +/- 0.1 hours, P less than .0001). Group 1 children were significantly more likely to vomit AC than were group 2 children (18 of 32 vs six of 38, P less than .001). Patients receiving SOI who were subsequently discharged spent significantly more time in the ED than those receiving only AC (4.1 +/- 0.2 vs 3.4 +/- 0.2 hours, P less than .05)., Conclusions: Ipecac delays the administration of AC, hinders its retention, and prolongs ED time in pediatric ingestion patients. These data support the recommendation that AC alone should be the gastrointestinal decontamination method of choice for the mild-to-moderate pediatric ingestion patient presenting to an ED.

The additional effect, if any, of subcutaneous, long-acting epinephrine (Sus-Phrine) to aerosolized albuterol for acute pediatric asthma was studied. Over an eight-month period, patients were enrolled in a prospective, randomized, controlled trial. All patients were recruited and studied in a pediatric emergency department. Forty-three children between the ages of three and 12 years, with a mean age of 8.9 years, presenting with acute asthma were enrolled. Group 1 received Sus-Phrine, 0.005 ml per kg before albuterol aerosols, as appropriate. Group 2 only received albuterol aerosols. There was no significant difference in the extent of improvement between the two groups at either 20 minutes or two hours for clinical score, peak flow, or respiratory rate. Subcutaneous, long-acting epinephrine provides no additional benefit to a beta-2 agonist by nebulization for children with acute asthma.

The clinical course of a five-month-old male with CSF otorrhea in the absence of head trauma is presented. The anatomy, workup, and management of this condition are described. The need to consider communication between the subarachnoid space and middle ear in any child with ear drainage, sensorineural hearing loss, or recurrent meningitis is emphasized.