Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV ...infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.
•Strong p16 expression can be seen in head and neck mesenchymal tumors.•HPV infection is not common in head and neck mesenchymal tumors.•p16 stain should not be used as a confirmatory tool for HPV infection in head and neck mesenchymal tumors.•HPV infection is not common in non-oropharyngeal spindle cell carcinomas.
Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver ...factors associated with the development of these symptoms.
This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II BDI-II), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay LOS), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months.
BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale P = .28 and Center for Epidemiologic Studies Depression Scale P = .74).
Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders.
Older patients in the intensive care unit are at greater risk of AKI; however, use of kidney replacement therapy in this population is poorly characterized. We describe the triggers and outcomes ...associated with kidney replacement therapy in older patients with AKI in the intensive care unit.
Our study was a prospective cohort study in 16 Canadian hospitals from September 2013 to November 2015. Patients were ≥65 years old, were critically ill, and had severe AKI; exclusion criteria were urgent kidney replacement therapy for a toxin and ESKD. We recorded triggers for kidney replacement therapy (primary exposure), reasons for not receiving kidney replacement therapy, 90-day mortality (primary outcome), and kidney recovery.
Of 499 patients, mean (SD) age was 75 (7) years old, Charlson comorbidity score was 3.0 (2.3), and median (interquartile range) Clinical Frailty Scale score was 4 (3-5). Most were receiving mechanical ventilation (64%;
=319) and vasoactive support (63%;
=314). Clinicians were willing to offer kidney replacement therapy to 361 (72%) patients, and 229 (46%) received kidney replacement therapy. Main triggers for kidney replacement therapy were oligoanuria, fluid overload, and acidemia, whereas main reasons for not receiving therapy were anticipated recovery (67%;
=181) and therapy not consistent with patient preferences for care (24%;
=66). Ninety-day mortality was similar in patients who did and did not receive kidney replacement therapy (50% versus 51%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.58 to 1.06); however, decisions to offer kidney replacement therapy varied significantly by patient mix, acuity, and perceived benefit. There were no differences in health-related quality of life or rehospitalization among survivors.
Most older, critically ill patients with severe AKI were perceived as candidates for kidney replacement therapy, and approximately one half received therapy. Both willingness to offer kidney replacement therapy and reasons for not starting showed heterogeneity due to a range in patient-specific factors and clinician perceptions of benefit.
OBJECTIVES: Tracheostomy is commonly performed in critically ill patients requiring prolonged mechanical ventilation (MV). We evaluated the outcomes of tracheostomy in patients who received greater ...than or equal to 1 week MV and were followed for 1 year. DESIGN: In this secondary analysis of a prospective observational study, we compared outcomes in tracheostomy versus nontracheostomy patients. Outcomes post ICU included Functional Independence Measure (FIM) subscales, 6-Minute Walk Test (6MWT), Short Form 36 (SF36), Medical Research Council (MRC) Scale, pulmonary function tests (PFTs), Impact of Event Scale (IES), Beck Depression Inventory-II (BDI-II), and vital status and disposition. SETTING: Nine University affiliated ICUs in Canada. PATIENTS: Medical/surgical patients requiring MV for 7 or more days who were enrolled in the Towards RECOVER Study. MEASUREMENTS AND MAIN RESULTS: Of 398 ICU survivors, 193 (48.5%) received tracheostomy, on median ICU day 14 (interquartile range IQR, 8–0 d). Patients with tracheostomy were older, had similar severity of illness, had longer MV duration and ICU and hospital stays, and had higher risk of ICU readmission (odds ratio OR, 1.9; 95% CI, 1.0–3.2) and hospital mortality (OR, 2.6; 95% CI, 1.1–6.1), but not 1-year mortality (hazard ratio, 1.41; 95% CI, 0.88–1.2). Over 1 year, tracheostomy patients had lower FIM-Total (7.7 points; 95% CI, 2.2–13.2); SF36, IES, and BDI-II were similar. From 3 months, tracheostomy patients had 12% lower 6MWT ( p = 0.0008) and lower MRC score (3.4 points; p = 0.006). Most PFTs were 5–8% lower in the tracheostomy group. Tracheostomy patients had similar specialist visits (rate ratio, 0.63; 95% CI, 0.28–2.4) and hospital readmissions (OR, 0.82; 95% CI, 0.54–1.3) but were less likely to be at home at hospital discharge and 1 year. CONCLUSIONS: Patients who received tracheostomy had more ICU and hospital care and higher hospital mortality compared with patients who did not receive a tracheostomy. In 1 year follow-up, tracheostomy patients required a higher daily burden of care, expressed by FIM.
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We ...imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222C (odds ratio (OR) = 2.36, P = 5.2 × 10−17), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10−20). rs78378222 is in the 3′ untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3′-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10−6), glioma (OR = 2.35, P = 1.0 × 10−5) and colorectal adenoma (OR = 1.39, P = 1.6 × 10−4). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver ...factors associated with the development of these symptoms.
This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II BDI-II), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay LOS), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months.
BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale P = .28 and Center for Epidemiologic Studies Depression Scale P = .74).
Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders.
Effects of microwave (MW) fields (continuous wave, 2.45 GHz, specific absorption rates 12.5 or 125 mW/g) on input resistances and action potential (AP) intervals of neurons in ganglia of snails ...(Helix aspersa), at 20.9+or-0.1 degrees C were studied. At 12.5 mW/g, input resistance did not change during irradiation, but increased (p<0.05) afterward. At 125 mW/g, input resistance during irradiation was lower than in unirradiated controls. Serial correlograms changed marginally more frequently in MW experiments than in controls, but the changes had no consistent pattern. The AP firing rate was affected by MW, but the direction was not consistent across cells. When AP generation was modeled as being due to a neuronal input current, MW did not affect its mean, standard deviation, or autocorrelation. Unlike MW, temperature changes caused neurons to respond robustly and reversibly. The data suggest that MW may enhance degenerative effects such as metabolic rundown or loss of ion channel patency, but do not indicate a specific mechanism for MW interaction with neurons.< >