Immature Platelets As a Predictor of Disease Severity and Mortality in Sepsis and Septic Shock: A Systematic Review.

Sepsis is associated with high morbidity and mortality, and short-term mortality remains above 30% despite relevant supportive and antibiotic treatments. The aim of this systematic review was to summarize and discuss the current evidence of the association of an increased number of circulating immature platelets with disease severity and mortality in patients with sepsis or septic shock. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered at the PROSPERO database (registration number: CRD42018104326). A systematic literature search was performed in PubMed, Web of Science, Scopus, and Embase on June 20, 2018, without time restrictions. The included studies were quality-assessed by the National Institutes of Health's Quality Assessment Tools. In total, 14 studies were included. The parameters used for the determination of platelet maturity were mean platelet volume, immature platelets fraction, reticulated platelet percentage, and absolute immature platelets count. Nine studies reported significantly increased immature platelet markers in nonsurvivors of septic shock compared with survivors, as well as in patients with severe sepsis or septic shock compared with patients without severe sepsis and septic shock. Six of these nine studies demonstrated that increased immature platelet markers were predictors of mortality and/or disease severity (area under the receiver operating curve: 0.599-0.886). This review suggests that an increased number of circulating immature platelets is associated with increased disease severity and mortality in patients with sepsis and septic shock. Larger studies are needed to confirm whether immature platelets should be routinely monitored to support the prediction of disease severity and mortality in septic patients.

First reported CABP2-related non-syndromic hearing loss in Northern Europe.

BACKGROUND: CABP2-related non-syndromic hearing loss have only been reported in a few families worldwide (Iran, Turkey, Pakistan and Italy). The hearing loss was in these cases described as prelingual, symmetrical, and moderate to severe. METHODS: Following DNA isolation, exome sequencing was performed in 123 genes related to non-syndromic hearing loss. Variant verification and carrier testing were performed by direct sequencing. RESULTS: We report the first Northern European individual with CABP2-related hearing loss: an 8-year-old Danish Caucasian boy with non-syndromic, prelingual, and sensorineural hearing loss, who is homozygous for the splice site variant CABP2: c. 637+1G>T previously found in three Iranian families and in one Pakistani family. Both parents are of Danish Caucasian origin with no known history of consanguinity. This is in contrast to the four reported Middle Eastern families, who all were consanguineous. However, loss of heterozygosity in a 3.2 Mb area on chromosome 11 including CABP2 was observed, suggesting a common parental ancestor. CONCLUSION: We report the first case of CABP2-related autosomal recessive hearing loss in Northern Europe. The index is of Danish Caucasian origin and found to be homozygous for the splice site variant c.637+1G>T.

Carcinoma of the nasal cavity and paranasal sinuses in Denmark 1995-2004.

OBJECTIVE: To evaluate the treatment outcome for sino-nasal carcinomas in Denmark from 1995-2004 and compare the results to the previous Danish survey covering 1982-1991. DESIGN: Retrospective follow-up. MATERIALS AND METHODS: In the five Danish head and neck oncology centres, charts of all consecutive patients with sino-nasal carcinomas were reviewed and data extracted to a common database. Altogether 242 patients from the period 1995-2004 were identified. Of these 162 (67%) were male and 80 (33%) female. Histologies included squamous cell carcinoma (55%), adenocarcinoma (28.5%), adenoid-cystic carcinoma (5.0%), undifferentiated carcinoma (4.5%), transitiocellular carcinoma (1.7%), mucoepidermoid carcinoma (0.8%), neuroendocrine carcinoma (2.5%), small cell carcinomas (1.2%) and carcinomas not otherwise specified (0.8%). Treatments included radiotherapy alone 79 (33%), surgery alone 29 (12%), combined surgery and radiotherapy 96 (40%), palliative/no treatment 38 (16%). A total of 204 (86%) patients were treated with curative intent. RESULTS: Of the 204 patients treated with curative intent, 94 (46%) relapsed. Most failures were in T-site (63, 30%). N-site failures were 10 (5%) and M-site failures six (3%). Failure occurring in T+N-site, T+M-site, N+M-site and T+N+M-site were seven (3%), two (1%), one (0.5%) and five (3%) respectively. The 5-year actuarial local, nodal and loco-regional control rates were 55 + or - 4%, 86 + or - 3%, 49 + or - 4%, respectively. The overall 5-year actuarial survival rate for the entire cohort was 47 + or - 3%, and the corresponding cancer-specific 5-year actuarial survival rate was 57 + or - 3%. Female gender, nasal cavity tumour, adenocarcinoma and low clinical stage were significant positive prognostic factors in univariate analysis. A Cox multivariate analysis showed that only tumour site and clinical stage were independent significant prognostic factors. CONCLUSION: The current series has confirmed stage and tumour site as independent prognostic factors. Compared to the previous Danish survey covering the period 1982-1991, the overall survival and cancer-specific survival rates have improved significantly.

Brief losartan treatment in young spontaneously hypertensive rats abates long-term blood pressure elevation by effects on renal vascular structure.

OBJECTIVE: We studied the importance of regional vascular structural changes for the long-term antihypertensive effect of brief angiotensin II receptor blockade with losartan in young spontaneously hypertensive rats (SHRs). DESIGN/METHODS: SHRs were treated from 3 to 8 weeks of age with losartan (SHRLos, 30 mg/kg per day in drinking water) or vehicle (SHRCon). Mean arterial blood pressure (MAP) was measured using a telemetric technique from 12 to 25 weeks of age. Indices of vascular structure in the renal and hindquarter limb (HQ) were assessed using a haemodynamic perfusion technique at 13-15 weeks of age. RESULTS: MAP in SHRLos was reduced by 20-30 mmHg throughout the study (P < 0.001) and left ventricular weights were reduced (P < 0.05). The slope of the pressure/flow relationship was significantly changed (P < 0.001) in both kidneys and HQ vascular beds, suggesting greater average lumen dimensions in SHRLos. Pressure-glomerular filtration rate (GFR) curves of SHRLos kidneys were shifted to the left (P < 0.001), suggesting that the reduction in renal vascular resistance was predominantly preglomerular. The changes in structural indices of the heart and HQ closely followed the reduction in MAP. However, resistance at maximal dilatation in SHRLos kidneys was changed out of proportion to the lowering in MAP (P < 0.01). CONCLUSIONS: Brief losartan treatment in young SHRs reduces long-term MAP. The reduced MAP is associated with higher average renal and skeletal muscle vascular dimensions at maximal dilatation, predominantly in the pre-capillary vasculature. The reduction in vascular resistance of the kidney appears to be out of proportion to the reduction in MAP and it may be speculated that this is of primary importance in the long-term hypotensive effect of brief angiotensin II antagonism in SHRs.