A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons

Breathing is maintained and controlled by a network of neurons in the brainstem that generate respiratory rhythm and provide regulatory input. Central chemoreception, the mechanism for CO(2) detection that provides an essential stimulatory input, is thought to involve neurons located near the medullary surface, whose nature is controversial. Good candidates are serotonergic medullary neurons and glutamatergic neurons in the parafacial region. Here, we show that mice bearing a mutation in Phox2b that causes congenital central hypoventilation syndrome in humans breathe irregularly, do not respond to an increase in CO(2), and die soon after birth from central apnea. They specifically lack Phox2b-expressing glutamatergic neurons located in the parafacial region, whereas other sites known or supposed to be involved in the control of breathing are anatomically normal. These data provide genetic evidence for the essential role of a specific population of medullary interneurons in driving proper breathing at birth and will be instrumental in understanding the etiopathology of congenital central hypoventilation syndrome.     

EMR of large sessile colorectal polyps

BACKGROUND: EMR optimizes histopathologic assessment of resected lesions. This study evaluated the outcome of EMR of large sessile colorectal polyps in terms of complications and recurrence. METHODS: An uncontrolled prospective study was conducted of a cohort of 136 patients with sessile colorectal polyps referred for EMR. After submucosal injection, EMR was performed piecemeal by either snare polypectomy alone or with cap aspiration. RESULTS: In 136 patients, a total of 139 sessile polyps were resected, 86 of which were in the right colon. Median polyps diameter was 20 mm in the right colon and 30 mm in the other colonic segments. Intraprocedure bleeding occurred after 15 polypectomies (10.8%) and was controlled endoscopically in all cases; there was no delayed bleeding. Post-polypectomy syndrome occurred in 5 patients (3.7%). There was no perforation. Invasive carcinoma was found in 17 sessile colorectal polyps, and surgery was performed in 10 of 17 cases. Follow-up colonoscopy in 93 patients without invasive carcinoma (96 polyps), over a median of 12.3 months, disclosed local recurrence of 21 adenomatous polyps (21.9%). Colonoscopic follow-up in 5 of the 7 patients, who had sessile colorectal polyps with invasive carcinoma and did not undergo surgery, disclosed no local recurrence. CONCLUSIONS: EMR, including EMR with cap aspiration, is effective and safe for removal of sessile colorectal polyps throughout the colon.     

Adrenalectomy for Clinically Isolated Metastasis from Colorectal Carcinoma: Report of Eight Cases

Purpose  Metastasis to the adrenal glands is a relatively frequent finding at autopsy. Adrenal metastasis of colorectal carcinoma is rare (14 percent). Isolated adrenal metastasis is even rarer, and presents a therapeutic dilemma. Methods  Between 1997 and 2006, eight patients (5 men; mean age, 62 years) underwent adrenalectomy for metastasis of colorectal carcinoma. The tumors were Stage D in four cases, Stage B in two cases, and Stage C in the remaining two. Adjuvant chemotherapy was instituted. Results  All patients were asymptomatic, and adrenal metastasis was suspected from an elevated serum level of carcinoembryogenic antigen or discovered by computed tomography. Adrenal metastases were metachronous in seven patients, with median disease-free interval of 3.75 years. At the time of follow-up, one patient remained alive and free of disease 12 months after adrenalectomy, one patient was lost to follow-up after 22 months, and 6 patients have died from malignancy. The mean survival for the patients who died was 32 months. Conclusions  The rarity of isolated adrenal metastasis of colorectal carcinoma makes a randomized, prospective trial comparing surgery vs. nonsurgical management highly unlikely. Our results provide further support for surgical resection of solitary adrenal metastasis, which may translate into survival benefit. Presented in part in abstract form at European Society of ColoProctology (ESCP) meeting. Lisbon, Portugal, September 13–15, 2006. Reprints are not available.     

Diagnostic accuracy of coronary in-stent restenosis using 64-slice computed tomography: comparison with invasive coronary angiography.

OBJECTIVES: This study sought to evaluate the diagnostic accuracy of coronary binary in-stent restenosis (ISR) with angiography using 64-slice multislice computed tomography coronary angiography (CTCA) compared with invasive coronary angiography (ICA). BACKGROUND: A noninvasive detection of ISR would result in an easier and safer way to conduct patient follow-up. METHODS: We performed CTCA in 81 patients after stent implantation, and 125 stented lesions were scanned. Two sets of images were reconstructed with different types of convolution kernels. On CTCA, neointimal proliferation was visually evaluated according to luminal contrast attenuation inside the stent. Lesions were graded as follows: grade 1, none or slight neointimal proliferation; grade 2, neointimal proliferation with no significant stenosis (<50%); grade 3, neointimal proliferation with moderate stenosis (> or =50%); and grade 4, neointimal proliferation with severe stenosis (> or =75%). Grades 3 and 4 were considered binary ISR. The diagnostic accuracy of CTCA compared with ICA was evaluated. RESULTS: By ICA, 24 ISRs were diagnosed. Sensitivity, specificity, positive predictive value, and negative predictive value were 92%, 81%, 54%, and 98% for the overall population, whereas values were 91%, 93%, 77%, and 98% when excluding unassessable segments (15 segments, 12%). For assessable segments, CTCA correctly diagnosed 20 of the 22 ISRs detected by ICA. Six lesions without ISR were overestimated as ISR by CTCA. As the grade of neointimal proliferation by CTCA increases, the median value of percent diameter stenosis increased linearly. CONCLUSIONS: Binary ISR can be excluded with high probability by CTCA, with a moderate rate of false-positive results.     

Management and outcomes of acute respiratory distress syndrome patients with and without comorbid conditions

Rationale

The standard of care for patients with acute respiratory distress syndrome (ARDS) has been developed based on studies that usually excluded patients with major comorbidities.

Objectives

To describe treatments and outcomes according to comorbidities in patients with ARDS admitted to 19 ICUs (1997–2014).

Methods

Patients were grouped based on comorbidities. Determinants of day-28 mortality were identified by multivariable Cox analysis stratified on center.

Measurements and main results

Among 4953 ARDS patients, 2545 (51.4%) had major comorbidities; the proportion with major comorbidities increased after 2008. Hematological malignancy was associated with severe ARDS and rescue therapies for refractory hypoxemia. COPD, HIV infection, and hematological malignancy were associated with a lower likelihood of invasive mechanical ventilation on the admission day. Admission-day SOFA score was higher in patients with major comorbidities, who more often received vasopressors, dialysis, or treatment-limitation decisions. Day-28 mortality was 33.7% overall, 27.2% in patients without major comorbidities, and 31.1% (COPD) to 56% (hematological malignancy) in patients with major comorbidities. By multivariable analysis, mortality was lower in patients with COPD and higher in those with chronic heart failure, solid tumors, or hematological malignancies. Mortality was independently associated with P_aO₂/F_iO₂ and PaCO₂ on day 1, ARDS of pulmonary origin, worse SOFA score, and ICU-acquired events.

Conclusions

Half the patients with ARDS had major comorbidities, which were associated with severe ARDS, multiple organ dysfunction, and day-28 mortality. These findings do not support the exclusion of ARDS patients with severe comorbidities from randomized clinical trials. Trials in ARDS patients with whatever comorbidities are warranted.