Brachytherapy and osteoradionecrosis in patients with base of tongue cancer.

BACKGROUND: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. AIMS: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. MATERIAL AND METHODS: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. RESULTS: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782). CONCLUSIONS AND SIGNIFICANCE: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Delivery mode and risk of gastrointestinal disease in the offspring.

INTRODUCTION: The global increase of individuals born by cesarean section with reported levels up to 20% of all deliveries, makes it important to study cesarean section and possible associations that can increase risk of subsequent diseases in children. The aim of the study was to evaluate if cesarean section is associated with increased risk of gastrointestinal disease later in life in a large population-based cohort. MATERIAL AND METHODS: In this national population-based cohort study including all full-term individuals registered in the Medical Birth Register in Sweden between 1990 and 2000, type of delivery (exposure) was collected from the Medical Birth Register. The study population was followed until 2017 with regards to the outcomes: inflammatory bowel disease (Crohn's disease or ulcerative colitis), appendicitis, cholecystitis, or diverticulitis registered in the Swedish National Patient Register. Cox proportional-hazards models compared disease-free survival time between exposed and unexposed. RESULTS: The final study population consisted of 1 102 468 individuals of whom 11.6% were delivered by cesarean section and 88.4% were vaginally delivered. In univariate analysis, cesarean section was associated with Crohn's disease (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.02-1.25), diverticulosis (HR 1.57, 95% CI 1.13-2.18), and cholecystitis (HR 1.16, 95% CI 1.05-1.28). However, the increased risk only remained for Crohn's disease after adjustment for confounders (HR 1.14, 95% CI 1.02-1.27). No associations between delivery mode and appendicitis, ulcerative colitis, cholecystitis, or diverticulosis were found in the multivariate analysis. CONCLUSIONS: Cesarean section is associated with Crohn's disease later in life, but no other association between delivery mode and gastrointestinal disorders later in life could be found.

Peri-operative oxygen consumption revisited: An observational study in elderly patients undergoing major abdominal surgery.

BACKGROUND: Monitoring oxygen consumption (VO2) is neither recommended nor included in peri-operative haemodynamic algorithms aiming at optimising oxygen delivery (DO2) in major abdominal surgery. Estimates of peri-operative VO2 changes are uncertain in earlier publications and have limited generalisability in the current high-risk surgical population. In a prospective non-interventional observational study in elderly patients undergoing major abdominal procedures, we investigated the change of VO2 after induction of anaesthesia and secondarily, the further changes during and after surgery in relation to DO2 and estimated oxygen extraction ratio (O2ER) by routine monitoring. METHODS: VO2 was determined by indirect calorimetry (QuarkRMR) in 20 patients more than 65 years (ASA II to IV), scheduled for elective open upper abdominal surgery with combined epidural and general anaesthesia. Data were collected during 20-minute periods pre-operatively and after anaesthesia induction, with subsequent measurements during surgery and postoperatively. Simultaneously, DO2 was monitored using LiDCOplus. The O2ER was estimated from arterial-central venous oxygen content calculation. Mixed models were used to analyse the peri-operative changes. RESULTS: VO2 decreased after induction of anaesthesia by a mean of 34% (95% CI, 28 to 39). After 2 h of surgery, VO2 was reduced by 24% (95% CI, 20 to 27) compared with the awake baseline measurements. Pre-operative mean DO2 was 440 (95% CI, 396 to 483) ml min m and decreased by a mean of 37% (95% CI, 30 to 43) during anaesthesia. The estimated O2ER did not change intra-operatively 0.24 (95% CI, 0.21 to 0.26) but increased postoperatively to 0.31 (95% CI, 0.27 to 0.36). The changes of VO2 were parallel with changes of DO2 and O2ER in the intra-operative period. CONCLUSION: General anaesthesia reduced VO2 by approximately a third in elderly patients undergoing major abdominal surgery. Parallel changes of intra-operative VO2 and delivery were demonstrated while oxygen extraction was low. The relevance of these changes needs further assessment in relation to outcomes and haemodynamic interventions. TRIAL REGISTRATION: Clinicaltrials.gov NCT03355118.

Population-based cohort study of the correlation between provision of care and the risk for complications after appendectomy in children.

PURPOSE: To investigate the impact of hospital administrative level and caseload of pediatric appendectomies on the morbidity and mortality after appendectomy in a population-based cohort of Swedish children. METHODS: Population-based cohort study including all Swedish children less than 15 years of age that underwent appendectomy for suspected appendicitis, 1987-2009. Patient characteristics and data on postoperative morbidity and mortality were collected from the Swedish National Patient Register and the Swedish Death Register. Primary endpoints were postoperative morbidity and mortality. Two explanatory variables were investigated: hospital administrative level and hospital annual caseload of pediatric appendectomies. Data were analyzed in regression models adjusting for available confounders. RESULTS: The cohort comprised 55,591 children. The risk for postoperative complications was reduced in specialized pediatric surgical centers and in high caseload centers, compared to other hospitals. There were only seven postoperative deaths within 90 days of appendectomy. CONCLUSIONS: We found clinically relevant risk reductions for reoperation and for readmission after appendectomy in specialized pediatric surgical centers. Importantly, the risk for postoperative complications was also reduced with increased hospital caseload, indicating that the merit from centralizing the management of pediatric appendectomies to specialized pediatric surgical centers may also be achieved by increasing hospital caseload of pediatric appendectomies in non-pediatric surgical units. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level II.

Intra- and Interobserver Agreement of SUV SPECT Quantitative SPECT/CT Processing Software, Applied in Clinical Settings for Patients with Solid Renal Tumors.

Quantification tools for SPECT/CT are a field of ongoing research among hybrid imaging techniques. A recent multicenter study evaluating SUV SPECT software on phantoms showed that quantitative SPECT/CT is reproducible in Hybrid Viewer software. The aim of our study was to evaluate the intra- and interobserver agreement of quantitative SUV SPECT measurements in clinical settings for patients with solid renal tumors. Methods: The evaluation was part of a study that examined the role of 99mTc-sestamibi SPECT/CT in the characterization of solid kidney tumors and the differentiation of renal oncocytomas from renal cell carcinomas. Quantitative evaluation of SUV measurements was performed in Hybrid Viewer PDR, version 2.5. Forty-eight renal lesions were identified and examined twice by 2 independent readers. The agreement of the SUV measurements, concerning renal tumors and adjacent renal parenchyma, was evaluated using the intraclass correlation coefficient (ICC). Results: ICC for SUVmax measurements by the same reader was 97%-99% for solid renal tumors and 92%-98% for ipsilateral healthy renal parenchyma. ICC for SUVmax measurements between readers was 87%-89% for solid renal tumors and 72%-73% for ipsilateral healthy renal parenchyma. Estimated ICC for SUVmean measurements of solid renal tumors was 95%-98% for the same reader and 86%-89% between readers. Similar results were found for SUVpeak measurements. Conclusion: The high ICCs indicate a strong agreement among SUV measurements for patients with solid renal lesions undergoing 99mTc-sestamibi SPECT/CT, not only for measurements by the same reader but also for measurements between 2 different readers.

Quality of life after microvascular mandibular reconstruction for osteoradionecrosis-A prospective study.

BACKGROUND: Reconstructive surgery for mandibular osteoradionecrosis is increasing; however, evidence regarding the impact on health-related quality of life is lacking. The current exploratory study prospectively investigates whether resection with reconstruction is associated with changes in HRQoL parameters for these patients. METHODS: Seventeen patients underwent microvascular reconstruction for mandibular osteoradionecrosis between 2012 and 2015, and 16 completed the EORTC quality of life questionnaires QLQ-C30 and QLQ-H&N35 1 month before and 1 year after surgery. RESULTS: Increases in emotional (P = 0.01) and social functioning (P = 0.004) were observed, together with improvements in the fatigue (P = 0.04), appetite loss (P = 0.02) and pain (P = 0.02) scores, as evaluated by the QLQ-C30. Pain reduction was further confirmed by the QLQ-H&N35 (P = 0.04), which also showed improved scores for feeling ill (P = 0.001) and sexual difficulties (P = 0.04). CONCLUSION: This exploratory study suggests that microvascular reconstruction after mandibular osteoradionecrosis may improve HRQoL, with an emphasis on pain reduction; however, further studies are needed.

The effects of general anaesthesia on oxygen consumption: A meta-analysis guiding future studies on perioperative oxygen transport.

BACKGROUND: Increased oxygen extraction, the ratio of consumption to delivery, has been associated with poor outcome after surgery. Oxygen consumption (VO2) can change in several ways in the perioperative period, but is seldom monitored directly in routine care. This study investigates the effects of general anaesthesia on VO2. METHODS: We searched PubMed, EMBASE, and Cochrane Library 1946-2018 for studies including VO2 measurements before and after anaesthesia induction. Quality was assessed by Cochrane risk of bias tool and NIH Quality Assessment tool for before-and-after studies. Changes in VO2 after anaesthesia induction were pooled in a random effects model meta-analysis with standardized mean differences transformed to absolute changes of VO2. Changes in VO2 after surgical incision and after recovery from anaesthesia were analysed as secondary outcomes in the included studies. RESULTS: Twenty-four studies including 453 patients were analysed for VO2 changes induced by anaesthesia. Studies were published during 1969-2000 and mean age of patients ranged 28-70 years. VO2 decreased after anaesthesia induction by -65 (-75; -55, 95% CI) mL min-1 and indexed VO2 (VO2I) by -33 (-38; -28, 95% CI) mL min-1  m-2 . After surgical incision and in the post-operative period VO2 increased again. Heterogeneity was considerable among the studies and the overall quality of evidence was very low. CONCLUSIONS: General anaesthesia probably reduces oxygen consumption but the effect estimate is uncertain. Given the limited generalizability and low quality of the available evidence, new studies in modern perioperative settings and in today's older high-risk surgical patient populations are needed.

Can STOP-Bang and Pulse Oximetry Detect and Exclude Obstructive Sleep Apnea?

BACKGROUND: Obstructive sleep apnea (OSA) is related to postoperative complications and is a common disorder. Most patients with sleep apnea are, however, undiagnosed, and there is a need for simple screening tools. We aimed to investigate whether STOP-Bang and oxygen desaturation index can identify subjects with OSA. METHODS: In this prospective, observational multicenter trial, 449 adult patients referred to a sleep clinic for evaluation of OSA were investigated with ambulatory polygraphy, including pulse oximetry and the STOP-Bang questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index >35 kg/m, Age >50 years, Neck circumference >40 cm, and male Gender. RESULTS: The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep apnea, defined as apnea-hypopnea index (AHI) ≥15, and the sensitivity and specificity for this score were 63% (95% CI, 0.55-0.70) and 69% (95% CI, 0.64-0.75), respectively. A STOP-Bang score of <2 had a probability of 95% (95% CI, 0.92-0.98) to exclude an AHI >15 and a STOP-Bang score of ≥6 had a specificity of 91% (95% CI, 0.87-0.94) for an AHI >15. The items contributing most to the STOP-Bang were the Bang items. There was a positive correlation between AHI versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman ρ 0.50 (95% CI, 0.43-0.58) and 0.96 (95% CI, 0.94-0.97), respectively. CONCLUSIONS: STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang score of <2 almost excludes moderate and severe OSA, whereas nearly all the patients with a STOP-Bang score ≥6 have OSA. We suggest the addition of nightly pulse oximetry in patients with a STOP-Bang score of 2-5 when there is a need for screening for sleep apnea (ie, before surgery).

Assessment of Cytokine and Chemokine Signatures as Potential Biomarkers of Childhood Community-acquired Pneumonia Severity: A Nested Cohort Study in India.

BACKGROUND: Pediatric community-acquired pneumonia (CAP) is a leading cause of childhood mortality in developing countries. In resource-poor settings, pneumonia diagnosis is commonly made clinically, based on World Health Organization guidelines, where breathing difficulty or cough and age-adjusted tachypnea suffice to establish diagnosis. Also, the severity of CAP is generally based on clinical features and existing biomarkers do not reliably correlate to either clinical severity or outcome. Here, we asked whether systemic immune and inflammatory mediators could act as biomarkers predicting CAP severity or outcome. METHODS: Serum from a subset of a CAP cohort (n = 196), enrolled in India, classified according to World Health Organization criteria as having pneumonia or severe pneumonia, was used for simultaneous measurement of 21 systemic cytokines and chemokines. RESULTS: We found significantly higher IL-6, IL-8, IL-13, IFN-γ and lower CCL22 concentrations in patients with severe compared with mild CAP (P values: 0.019, 0.036, 0.006, 0.016 and 0.003, respectively). Based on higher MIP-1α, IL-8, IL-17 or lower CCL22 response pattern at the time of enrolment, children with fatal outcome showed markedly different pattern of inflammatory response compared with children classified with the same disease severity, but with nonfatal outcome (P values: 0.043, 0.017, 0.008 and 0.020, respectively). CONCLUSIONS: Our results suggest a relation between an elevated mixed cytokine response and CAP severity on one hand, and a bias toward uncontrolled neutrophilic inflammation in subjects with fatal outcome on the other. Collectively our findings contribute to increased knowledge on new biomarkers that can potentially predict severity and outcome of childhood CAP in the future.

Sedation with Dexmedetomidine or Propofol Impairs Hypoxic Control of Breathing in Healthy Male Volunteers: A Nonblinded, Randomized Crossover Study.

BACKGROUND: In contrast to general anesthetics such as propofol, dexmedetomidine when used for sedation has been put forward as a drug with minimal effects on respiration. To obtain a more comprehensive understanding of the regulation of breathing during sedation with dexmedetomidine, the authors compared ventilatory responses to hypoxia and hypercapnia during sedation with dexmedetomidine and propofol. METHODS: Eleven healthy male volunteers entered this randomized crossover study. Sedation was administered as an intravenous bolus followed by an infusion and monitored by Observer's Assessment of Alertness/Sedation (OAA/S) scale, Richmond Agitation Sedation Scale, and Bispectral Index Score. Hypoxic and hypercapnic ventilatory responses were measured at rest, during sedation (OAA/S 2 to 4), and after recovery. Drug exposure was verified with concentration analysis in plasma. RESULTS: Ten subjects completed the study. The OAA/S at the sedation goal was 3 (3 to 4) (median [minimum to maximum]) for both drugs. Bispectral Index Score was 82 ± 8 and 75 ± 3, and the drug concentrations in plasma at the sedation target were 0.66 ± 0.14 and 1.26 ± 0.36 µg/ml for dexmedetomidine and propofol, respectively. Compared with baseline, sedation reduced hypoxic ventilation to 59 and 53% and the hypercapnic ventilation to 82 and 86% for dexmedetomidine and propofol, respectively. In addition, some volunteers displayed upper airway obstruction and episodes of apnea during sedation. CONCLUSIONS: Dexmedetomidine-induced sedation reduces ventilatory responses to hypoxia and hypercapnia to a similar extent as sedation with propofol. This finding implies that sedation with dexmedetomidine interacts with both peripheral and central control of breathing.

Maternal Risk Factors and Perinatal Characteristics for Hirschsprung Disease.

BACKGROUND AND OBJECTIVES: Hirschsprung disease (HSCR) is a congenital defect of the enteric nervous system characterized by a lack of ganglion cells in the distal hindgut. The aim of this study was to assess the birth prevalence, perinatal characteristics, and maternal risk factors in HSCR patients in Sweden. METHODS: This was a nationwide, population-based, case-control study of all children born in Sweden between 1982 and 2012 and registered in the Swedish Medical Birth Register. Cases were identified in the Swedish National Patient Register and data on potential maternal risk factors and patient characteristics were collected from the Swedish National Patient Register and the Swedish Medical Birth Register. Five age- and sex-matched controls were randomly selected for each case. The association between studied risk factors and HSCR was analyzed using conditional logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: The study population comprised 600 HSCR cases and 3000 controls with a male-to-female ratio of 3.7:1. The birth prevalence of HSCR was 1.91/10 000. Maternal obesity was associated with an increased risk for the child to have HSCR (OR 1.74; CI 1.25-2.44). Children with HSCR were born at an earlier gestational age (OR 1.60; CI 1.18-2.17) than control children. Associated malformations were identified in 34.5% of the cases. CONCLUSIONS: This study showed that the Swedish birth prevalence of HSCR was 1.91/10 000. Children with HSCR disease were born at a lower gestational age than controls. Maternal obesity may increase the risk for the child to have HSCR.

Etiology of community acquired pneumonia among children in India: prospective, cohort study.

BACKGROUND: Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. METHODS: We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. FINDINGS: We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae-3, CMV-3, S. aureus-2, H. influenzae-2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. CONCLUSIONS: The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.

Predicting Outcome in Colonoscopic High-risk Surveillance.

AIM: Surveillance with colonoscopy in risk groups for colorectal cancer needs to be based on an adequate selection of individuals to examine and a well-devised timing. To stratify the risk of finding neoplasia at colonoscopy, a cohort with increased familial risk of colorectal cancer was studied. PATIENTS AND METHODS: Based on family history, 1,203 individuals with at least two-fold increased risk of colorectal cancer were offered regular colonoscopies. The impact of different variables in the family history was assessed by logistic regression for the prevalence of adenoma and advanced adenoma. Findings at first colonoscopy were assessed regarding the association with risk of future lesions. RESULTS: The prevalence of advanced lesions, when controlling for age, was associated with the number of first-degree relatives with colorectal cancer, with an age below 50 years for the youngest family member with colorectal cancer, but not with gender. Family history had a low impact on the prevalence of simple adenoma. The risk of future advanced lesions was only associated with the prevalence of advanced lesions at the screening colonoscopy, whereas a finding of subsequent adenoma was associated with advanced lesions, adenomas and hyperplastic polyps. CONCLUSION: Adenomas and advanced lesions were not associated with the same risk factors. In the present study, the most important risk factors for advanced lesions, including cancer, were the number of first-degree relatives and a young family member with colorectal cancer. Findings of simple adenomas and hyperplastic polyps did not seem to be associated with subsequent advanced lesions.

PCBaSe Sweden: a register-based resource for prostate cancer research.

Objective. To construct a database for clinical epidemiological prostate cancer research based on linkages between the National Prostate Cancer Register (NPCR) of Sweden, a population-based, nationwide quality database, and other nationwide registries. Material and methods. By use of the individually unique Swedish Personal Identity Number, the NPCR was linked to the Swedish Cancer Registry, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register and the Acute Myocardial Infarction Register, all held at the Centre for Epidemiology at the National Board of Health and Welfare, and the Register of the Total Population, the Longitudinal Integration Database for Health Insurance and Labor Market Studies and the Multi-Generation Register, held at Statistics Sweden, and to the Swedish Hernia Register. Results. Record linkages between the NPCR and the Swedish Cancer Registry, the Cause of Death Register and the Register of the Total Population generated a database, named PCBaSe Sweden, including 80 079 prostate cancer cases, diagnosed between 1 January 1996 and 31 December 2006. Record linkage between PCBaSe Sweden and the Prescribed Drug Register generated 59 721 unique matches and linkage to the Acute Myocardial Infarction Register resulted in 11 459 matches. Conclusion. PCBaSe Sweden is a newly created and unique database with over 80 000 cases of prostate cancer with comprehensive data on inpatient and outpatient care, patterns of use of prescribed drugs and socioeconomic and familial factors. Many topics in clinical prostate cancer epidemiology can be investigated. using PCBaSe Sweden.