SMIM1 absence is associated with reduced energy expenditure and excess weight.

BACKGROUND: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. METHODS: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. FINDINGS: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. CONCLUSION: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

The K9-Teen Pandemic: When Good Boy Goes Bad. The Epidemiology, Management and Public Health Ramifications of Facial Dog Bite Injuries: Newcastle, Australia, Experience.

The purpose of this study was to investigate the epidemiology, pattern of injury and management of facial dog bite injuries. Methods: The authors conducted a retrospective cohort study over a 5-year period of patients who sustained a facial dog bite injury. The study setting was an Oral and Maxillofacial Surgery Department at a level 1 trauma centre, servicing an estimated catchment population in excess of 950,000 people. Results: In total, 171 patients were managed in the designated period from January 2017 to January 2022. The median age was 9 years (range 11 months to 77 years), with the highest incidence of a single age 4 years. The frequency was slightly greater amongst males (n = 93) than females (n = 78). The most common responsible breed were Pitbull types (n = 26). Overall, bites most often resulted from the family dog (n = 87), in the victim's own home (n = 84) and whilst playing with the dog (n = 64). The primary sites involved were the lips (n = 70), cheek (n = 53) and nose, representing the so called 'target area'. In 53 cases, the injuries were classified as severe. 138 patients required hospital admission, and of these, 130 required surgical management under general anaesthesia. Conclusions: Facial dog bite injuries present a significant burden on the healthcare system and result in physical, functional and/or emotional distress for the patient. As the rates of dog ownership continue to rise, a consequential increase in these injuries is also likely. Further, public health intervention is essential, particularly as the most susceptible demographic remains young male children.

The Impact of Global Collaboration on the Academic Focus of the West African College of Surgeons: Are Worldwide Efforts Aligning with Local Priorities?

BACKGROUND: Global collaboration has the potential to induce a shift in research focus away from the priorities of those in low- and low-middle-income countries (LICs and LMICs). This study quantified international collaboration among surgery publications by Fellows of the West African College of Surgeons (WACS) and investigated if collaboration with upper-middle-income and high-income countries (UMICs and HICs) decreases the homophily of research focus. METHODS: Publications by WACS surgery Fellows from 1960 to 2019 were characterized as local WACS publications, collaborative publications without UMIC/HIC participation, or collaborative publications with UMIC/HIC participation. Research topics were determined for each publication, and topic percentages were compared between collaboration groups. RESULTS: We analyzed 5065 publications. Most (3690 publications, 73%) were local WACS publications, while 742 (15%) were collaborative publications with UMIC/HIC participation and 633 (12%) were collaborative publications without UMIC/HIC participation. UMIC/HIC collaborations contributed to 49% of the increase (378 out of 766 publications) from 2000 to 2019. Topic homophily was significantly lower between local WACS publications and collaborations with UMIC/HIC participation (differed in nine research topics) than it was between local WACS publications and collaborations without UMIC/HIC participation (differed in two research topics). CONCLUSIONS: Publications without international collaboration comprise most WACS research, but the rate of UMIC/HIC collaborations is rapidly increasing. We found that UMIC/HIC collaborations decreased the homophily of topic focus in WACS publications, indicating that global collaborations need to have greater emphasis on the priorities of those in LICs and LMICs.

Systematic Review and Meta-Analysis on the Incidence of Level-Specific Cervical Nodal Metastasis in Primary Parotid Malignancies.

OBJECTIVE: In primary parotid gland malignancies, the incidence of level-specific cervical lymph node metastasis in clinically node-positive necks remains unclear. This study aimed to determine the incidence of level-specific cervical node metastasis in clinically node-negative (cN0) and node-positive (cN+) patients who presented with primary parotid malignancies. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, PubMed, Cochrane). REVIEW METHODS: Random-effects meta-analysis was used to calculate pooled estimate incidence of level-specific nodal metastasis for parotid malignancies with 95% confidence intervals (CIs). Subgroup analyses of cN0 and cN+ were performed. RESULTS: Thirteen publications consisting of 818 patients were included. The overall incidence of cervical nodal involvement in all neck dissections was 47% (95% CI, 31%-63%). Among those who were cN+, the incidence of nodal positivity was 89% (95% CI, 75%-98%). Those who were cN0 had an incidence of 32% (95% CI, 14%-53%). In cN+ patients, the incidence of nodal metastasis was high at all levels (level I 33%, level II 73%, level III 48%, level IV 39%, and level V 37%). In cN0 patients, the incidence of nodal metastasis was highest at levels II (28%) and III (11%). CONCLUSION: For primary parotid malignancies, the incidence of occult metastases was 32% compared to 89% in a clinically positive neck. It is recommended that individuals with a primary parotid malignancy requiring elective treatment of the neck have a selective neck dissection which involves levels II to III, with the inclusion of level IV based on clinical judgment. Those undergoing a therapeutic neck dissection should undergo a comprehensive neck dissection (levels I-V).

Comparison of postoperative complications in early versus delayed tracheostomy decannulation in patients undergoing oral cancer surgery with microvascular reconstruction.

The purpose of this study was to determine the relationship of early and delayed tracheostomy decannulation protocols on the length of stay, time to oral feeding and incidence of postoperative complications in patients undergoing microvascular reconstruction for oral cancer. A review of all patients who underwent surgical management of oral squamous cell carcinoma (OSCC) over the study period from 01/07/2017 to 31/06/2021 was performed. Patients who underwent elective tracheostomy as part of their microvascular reconstruction were included. Two cohorts were identified based on distinct postoperative tracheostomy decannulation protocols; early (Within 7 days) and delayed (≥7 days). Time to oral feeding, length of stay and complication rates was determined for both groups for statistical analysis. A total of 103 patients with OSCC were included in the study. The overall complication rate was 35.9% and were more likely in node positive patients (53.7% vs 23.2%; p = 0.003) and in cases where the geniohyoid muscle complex was disrupted during tumour resection (66.7% vs 31.9%; p = 0.026). Early decannulation was significantly associated with shorter length of hospital stay (10 days vs 15 days) and earlier removal of nasogastric feeding tubes (7 vs 10 days). There was no difference in the overall complication rate between the two groups (33.3% vs 37.5%; p = 0.833). Early decannulation in appropriately selected patients is recommended as it significantly reduces the length of hospital stay and aids in early resumption of oral intake. Furthermore, this approach is not associated with increased rates of complications.

Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission.

OBJECTIVES: We investigated whether soluble immune checkpoints (sICPs) predict treatment resistance, relapse and infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). METHODS: Plasma sICP concentrations from available samples obtained during conduct of the RAVE trial were measured by immunoabsorbent assays from patients with either proteinase 3 (PR3) or myeloperoxidase (MPO)-ANCA vasculitis and were correlated with clinical outcomes, a set of biomarkers and available flow cytometry analyses focusing on T cell subsets. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J. RESULTS: Analysis of 189 plasma samples at baseline revealed higher concentrations of sTim-3, sCD27, sLag-3, sPD-1 and sPD-L2 in patients with MPO-ANCA vasculitis (n=62) as compared with PR3-ANCA vasculitis (n=127). Among patients receiving rituximab induction therapy (n=95), the combination of lower soluble (s)Lag-3 (<90 pg/mL) and higher sCD27 (>3000 pg/mL) predicted therapy failure. Twenty-four out of 73 patients (32.9%) in the rituximab arm reaching remission at 6 months relapsed during follow-up. In this subgroup, high baseline values of sTim-3 (>1200 pg/mL), sCD27 (>1250 pg/mL) and sBTLA (>1000 pg/mL) were associated with both sustained remission and infectious complications. These findings could not be replicated in 94 patients randomised to receive cyclophosphamide/azathioprine. CONCLUSIONS: Patients with AAV treated with rituximab achieved remission less frequently when concentrations of sLag-3 were low and concentrations of sCD27 were high. Higher concentrations of sTim-3, sCD27 and sBTLA at baseline predicted relapse in patients treated with rituximab. These results require confirmation but may contribute to a personalised treatment approach of AAV.

Late Free Flap Failure in Head and Neck Reconstruction: Unusual Etiology in Two Case Studies and Literature Review.

The development of modern microvascular surgical techniques has enabled the reliable transfer of free vascularized tissue. This allowed for predictable reconstruction outcomes with excellent surgical success rates. However, devastating consequences of partial or total flap failure and subsequent loss may occur. This usually occurs in the first 48-72 h post-operatively. It is rare for flaps to fail in the late post-operative period and it remains poorly understood why flaps fail after day seven. We presented two patients in whom flap failure occurred after the seventh post-operative day (POD). Complete flap failure occurred after POD 9 and 27 in our cases. During the postoperative period, there was no evidence of early occlusion or insult to the vascular integrity such as venous/arterial compression. The cause of late flap failure was due to thrombophlebitis secondary to infection from the tracheostomy-neck fistula. This assumption was supported by recurrent failure of anastomoses revision.

Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors.

Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above ("high") and below ("low") the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with "high" CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with "low" CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce "high" IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce "low" IRT CFFNs.

Falls From Height, Facial Injuries and Fatalities: An Institutional Review.

Study Design: Retrospective cohort review. Objective: To investigate the relationship between falls from height and facial injuries. Methods: This is a retrospective cohort study, conducted over a 7-year period, of the medical records of all patients who presented to hospital for a maxillofacial injury following a fall from height. Fall heights were classified as low falls (1-3 m), high falls (3-10 m) and very high falls (≥10 m). Results: A total of 111 patients with 218 facial bone fractures were identified (78 men, 33 women and mean age 50.3 years). High falls were the most common (n = 58, 52.3%). Multiple fractures were identified in 51 (46.0%) patients. Orbital and middle third fractures were the most prevalent. Nasal, mandible, bilateral and fractures involving more than one facial third, increased as fall height increased, as did the requirement for operative fixation. The majority of patients had an associated injury (n = 100, 90.1%) and overall mortality was 6.3%. Conclusions: Falls from height are prevalent and there is a trend towards increased severity of facial injury, surgical intervention and associated morbidity as fall height increases. Falls from height are a significant public health concern and an important facet of maxillofacial trauma to recognise, as is the requirement for an interdisciplinary approach as they present to hospital.

CRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythemia.

The process of platelet production has so far been understood to be a 2-stage process: megakaryocyte maturation from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the peripheral blood platelet count. Proplatelet formation releases into the bloodstream beads-on-a-string preplatelets, which undergo fission into mature platelets. For the first time, we show that preplatelet maturation is a third, tightly regulated, critical process akin to cytokinesis that regulates platelet count. We show that deficiency in cytokine receptor-like factor 3 (CRLF3) in mice leads to an isolated and sustained 25% to 48% reduction in the platelet count without any effect on other blood cell lineages. We show that Crlf3-/- preplatelets have increased microtubule stability, possibly because of increased microtubule glutamylation via the interaction of CRLF3 with key members of the Hippo pathway. Using a mouse model of JAK2 V617F essential thrombocythemia, we show that a lack of CRLF3 leads to long-term lineage-specific normalization of the platelet count. We thereby postulate that targeting CRLF3 has therapeutic potential for treatment of thrombocythemia.

Serum Biomarkers of Disease Activity in Longitudinal Assessment of Patients with ANCA-Associated Vasculitis.

OBJECTIVE: Improved biomarkers of current disease activity and prediction of relapse are needed in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). For clinical relevance, biomarkers must perform well longitudinally in patients on treatment and in patients with nonsevere flares. METHODS: Twenty-two proteins were measured in 347 serum samples from 74 patients with AAV enrolled in a clinical trial. Samples were collected at Month 6 after remission induction, then every 3 months until Month 18, or at the time of flare. Associations of protein concentrations with concurrent disease activity and with future flare were analyzed using mixed-effects models, Cox proportional hazards models, and conditional logistic regression. RESULTS: Forty-two patients had flares during the 12-month follow-up period, and 32 remained in remission. Twenty-two patients had severe flares. Six experimental markers (CXCL13, IL-6, IL-8, IL-15, IL-18BP, and matrix metalloproteinase-3 [MMP-3]) and ESR were associated with disease activity using all three methods (P < 0.05, with P < 0.01 in at least one method). A rise in IL-8, IL-15, or IL-18BP was associated temporally with flare. Combining C-reactive protein (CRP), IL-18BP, neutrophil gelatinase-associated lipocalin (NGAL), and sIL-2Rα improved association with active AAV. CXCL13 and MMP-3 were increased during treatment with prednisone, independent of disease activity. Marker concentrations during remission were not predictive of future flare. CONCLUSION: Serum biomarkers of inflammation and tissue damage and repair have been previously shown to be strongly associated with severe active AAV were less strongly associated with active AAV in a longitudinal study that included mild flares and varying treatment. Markers rising contemporaneously with flare or with an improved association in combination merit further study.

Molecular Dosimetry of DNA Adducts in Rats Exposed to Vinyl Acetate Monomer.

Vinyl acetate monomer (VAM) is heavily used to synthesize polymers. Previous studies have shown that inhaled VAM, being metabolized to acetaldehyde, may form DNA adducts including N2-ethylidene-deoxyguanosine (N2-EtD-dG), which may subsequently cause mutations and contribute to its carcinogenesis. Currently, there is little knowledge on the molecular dosimetry between VAM exposure and DNA adducts under dosages relevant to human exposure. In this study, 0.02, 0.1, 1, 10, 50, 200, and 600 ppm VAM were exposed to rats by inhalation for 14 days (6 h/day). The use of [13C2]-VAM allows unambiguous differentiation and quantification of the exogenous and endogenous N2-EtD-dG by highly sensitive LC-MS/MS. Our data indicate that VAM-induced exogenous DNA adducts were formed in a non-linear manner. Exogenous DNA adducts were only detected in the nasal epithelium of rats exposed to 10, 50, 200, and 600 ppm VAM, whereas endogenous adducts were found in all nasal and other tissues analyzed. In addition, ratios of exogenous/endogenous DNA adducts were less than 1 with the dose up to 50 ppm, indicating that endogenous DNA adducts are predominant at low VAM concentrations. Moreover, differential dose-response in terms of exogenous DNA adduct formation were observed between nasal respiratory and olfactory epithelium. Furthermore, the lack of exogenous DNA adducts in distant tissues, including peripheral blood mononuclear cells, liver, brain, and bone marrow, indicates that VAM and/or its metabolite do not distribute systemically to cause DNA damage in distant tissues. Together, these results provided new molecular dosimetry to improve science-based cancer risk assessments of VAM.

Surgical subspecialists in West Africa: Workforce size, training opportunities, and contributing factors.

BACKGROUND: The global burden of disease treatable by surgical subspecialists remains an outstanding area of need, and yet little is known about the subspecialist workforce worldwide, especially in sub-Saharan Africa. This study aims to quantify the subspecialty surgical workforce and number of subspecialty training programs in West Africa and to identify socioeconomic factors predicting the number of subspecialists in West African countries. METHODS: West African subspecialists and accredited fellowship training programs in 17 West African countries were quantified using membership data from the West African College of Surgeons and compared with publicly available workforce data from the United States, the United Kingdom, and East, Central, and Southern Africa. Spearman's coefficients were calculated to identify socioeconomic predictors of subspecialist surgical workforce. RESULTS: Of 2,181 surgeons, 712 (32.6%) were surgical subspecialists. Three (18%) of 17 West African countries had greater than 11 subspecialists. There were 174 subspecialty training programs in the region, though 13 countries (76%) had no programs. The number of subspecialists correlated most strongly with the number of subspecialty training programs (rS = 0.68, P = .003) but also correlated significantly with gross population and number of medical schools (rS = 0.50-0.52, P ≤ .05). CONCLUSION: Subspecialist surgeons represent one third of surgeons in West Africa, though most countries have fewer than 12 providers. The number of subspecialists is significantly correlated with the number of subspecialty training programs, and yet many West African countries lack accredited programs. These results suggest that investing in training programs is the most valuable potential strategy to address the shortage of surgical subspecialists in West Africa.

The Implementation of COVID-19 Social Distancing Measures Changed the Frequency and the Characteristics of Facial Injury: The Newcastle (Australia) Experience.

STUDY DESIGN: A retrospective study was undertaken of a cohort of facially injured patients using matched 8-week periods: non-COVID (2019) and COVID (2020). OBJECTIVE: To determine whether there were any changes to the frequency and characteristics of facial injury due to the imposition of COVID-19 social distancing measures. METHODS: The primary predictor variable was an 8-week period of COVID-19 social distancing. The primary outcome variable was the sustaining of a facial injury. Demographic (age/gender) and injury characteristics (mechanism, site, and treatment) were also studied. Descriptive statistical analysis was undertaken and comparison made using Pearson χ2 and Fisher's exact tests. RESULTS: The number of facial injuries decreased from 103 (2019) to 73 (2020). There were statistically significant differences in changes over time for the 8-week periods. There were some clinically apparent differences seen in the characteristics of facial injuries. CONCLUSIONS: The imposition of COVID-19 social distancing changed the frequency and characteristics of facial injury.

To What Extent Does Illicit Drug Use Predispose to Facial Injury? An Institutional Investigation for an Emergent Problem.

STUDY DESIGN: There are potential substantive linkages between illicit drug use and the occurrence of injury. OBJECTIVE: The purpose of our study was to determine the prevalence, class of illicit drugs abused, and demographics in relation to a cohort of patients who sustained facial injury. METHODS: The authors undertook a retrospective observational study of a prospectively accessioned cohort of patients who had sustained a facial injury and presented to the John Hunter Hospital (Newcastle, NSW, Australia). The primary predictor variable was the presentation of a facial injury and the secondary outcome variables included illicit drug use, alcohol use, and socioeconomic factors. The study was carried out over a 12-month period. A descriptive analysis was undertaken on the assembled data. RESULTS: Of the 465 patient medical records that were accessed for the study, 348 were male and 117 were female. Their average age was 42.6 years: 5.8% (n = 27) were under the influence of illicit drugs at the time of their presentation and 13.1% (n = 61) admitted to an intercurrent illicit drug habit. Those who were under the combined influence of alcohol and drugs comprised of 2.8% (n = 13). CONCLUSIONS: Our study found that illicit drug use plays a small, but nonetheless, demonstrable role in the presentation of maxillofacial trauma patients to an urban level I trauma center. Illicit drug users are an emergent sociodemographic group of patients who can sustain facial trauma and their presentation needs to be appropriately considered, assessed, and managed collectively.

Systematic Generation of the Dunham Coefficients Using Symbolic Mathematics Software.

The Dunham coefficients are an indispensable part of the analysis of the ro-vibrational spectrum of a diatomic molecule. They provide a direct connection between the ro-vibrational states observed and the interatomic potential that must exist in the molecule. One may deduce the interatomic potential from the spectrum or, alternatively, predict the spectrum from a theoretically generated interatomic potential. The coefficients result from a mathematical analysis of the Schrödinger equation for such a system. Dunham's derivation relied on the WKB approximation and, as such, was subject to the associated limitations. In this paper, the quantum condition is derived without any reliance on the WKB approximation, using only principles of complex analysis. This sidesteps the need for introducing an approximate function to join solutions and suggests that the expansion has a more fundamental basis. Also in this paper, a mathematical algorithm for generating the Dunham coefficients is elaborated in detail. Careful attention is paid to keeping these coefficients accurate to a specified order in the smallness parameter, τe = Be/ωe. This algorithm is intended to be presented in a way that makes it amenable to incorporation into computer code and points where the efficiency can be improved are indicated. Coefficients have been generated and presented in the literature through the years. The current paper presents the coefficients explicitly to tenth order in the smallness parameter, far more than have been generated in any previous work.

LC-MS/MS Analysis of the Formation and Loss of DNA Adducts in Rats Exposed to Vinyl Acetate Monomer through Inhalation.

Formation of DNA adducts is a key event during carcinogenesis. DNA adducts, if not repaired properly, can lead to mutations and cancer. DNA adducts have been frequently used as biomarkers to evaluate chemical exposure. Vinyl acetate monomer (VAM) is widely used in the manufacture of various industrial polymers. Previous studies have documented that VAM induced nasal tumors in rodents exposed to high exposure levels of VAM. VAM is metabolized by carboxylesterase to acetaldehyde (AA), which subsequently results in DNA adducts. However, AA is also an endogenous metabolite in living cells, which impedes accurate assessment of the contribution of VAM exposure under the substantial endogenous background. To address this challenge, we exposed rats to stable isotope labeled [13C2]-VAM at 50, 200, and 400 ppm through inhalation for 6 h, followed by DNA adduct analysis in nasal respiratory and olfactory epithelia with highly sensitive mass spectrometry. Our results show that exogenous N2-ethyl-dG adducts were present in all rats exposed to [13C2]-VAM, with over 2-fold higher DNA adducts in nasal respiratory epithelium than olfactory epithelium. Our data also show that N2-ethyl-dG is a more sensitive biomarker to assess VAM exposure than 1,N2-propano-dG adducts. Moreover, a very low amount of exogenous N2-ethyl-dG adducts were detected in peripheral blood mononuclear cell samples of exposed rats, suggesting that only an extremely small percentage of [13C2]-VAM or its metabolite may enter into systemic circulation to potentially damage tissues beyond nasal epithelium. Furthermore, exogenous N2-ethyl-dG DNA adducts undergo rapid repair or spontaneous loss in nasal epithelium of exposed rats. Taken together, the results presented herein provide novel quantitative data and lay the foundation for future studies to improve risk assessment of VAM.

Epithelial Alteration Associated With Recovery From Laryngeal Squamous Metaplasia in Rats: Kinetics of Recovery From a Test Item-Related Change.

Squamous metaplasia is a nonspecific adaptive response to chronic irritation in the larynx and is often diagnosed as a test item-related change in rat inhalation studies. Investigating scientists are frequently asked to assess the adversity of laryngeal squamous metaplasia and to interpret its relevance to human risk. One factor in predicting relevance to human risk is the kinetics (degree and speed) of recovery following the cessation of exposure to the test item. Most reports describing recovery from squamous metaplasia in the rat larynx discuss the more severe end of the spectrum of metaplastic change (moderate to severe) and include relatively long (6 weeks or more) recovery periods. We conducted 2 studies to evaluate the toxicity and recovery from any potential effects of 4-(Chloro-2-methylphenoxy) butyric (MCPB) acid, a herbicide, when administered by inhalation to young male Sprague Dawley rats for 3 to 4 weeks. The studies resulted in minimal to moderate laryngeal squamous metaplasia for which we describe the kinetics of recovery over 1 to 4 weeks. We found that the microscopic change epithelial alteration, which is normally considered to be a precursor in the development of squamous metaplasia, can occur as a transitional stage between squamous and normal epithelium during recovery.

Postoperative Delirium is Associated With Prolonged Head and Neck Resection and Reconstruction Surgery: An Institutional Study.

PURPOSE: Delirium is a recognized complication of surgery. It has a deleterious effect on a patient's postoperative recovery and well-being. The purpose of this study was to estimate the frequency and identify the risk factors for the development of postoperative delirium (POD) in a cohort of patients who underwent extensive head and neck surgery (HNS) of greater than five hours duration. MATERIALS AND METHODS: The authors undertook a retrospective cohort study of patients who underwent HNS of greater than five hours duration. The primary predictor variables comprised a set of risk factors (sociodemographic, disease-specific, duration of surgery, and duration of inpatient stay) that were thought to be associated with the development of POD. The primary outcome variable was the development of POD. Descriptive, bivariate, and multivariate statistical analysis was undertaken, and significance was set at P < .05. RESULTS: One hundred and seventy patients were included in the study. There were 124 males and 46 females. Forty patients (23.53%) developed POD: 30 documented and 10 inferred. The mean age of the POD cohort was 65 years (SD 13), with a median age of 69 years. The occurrence of POD was statistically related to increased age, mental health status, American Society of Anesthesiologists (ASA) score, and drug dependence (either illicit or prescription). POD and operative duration were statistically associated. POD and length of stay were not statistically associated. CONCLUSION: Delirium did occur postoperatively in 23.53% of our patients who underwent extensive and prolonged HNS. POD may go unrecognized by treating teams. As POD has a deleterious effect on the cognitive function, it is important to identify and aggressively treat episodes of POD that occur during a patient's postoperative recovery.

Improving screening for physical impairments and access to early physiotherapy after neck dissection surgery: a translational controlled trial.

PURPOSE: Lack of routine screening for a range of physical impairments that can result after neck dissection (ND) may hinder physiotherapy referral and treatment. The purpose of this study was to implement an intervention that targeted both physiotherapists and surgeons to increase their post-operative physical screening of ND patients and in turn improve physiotherapy referral rates. METHODS: The authors undertook a translational controlled pilot study, conducted over a 12-month period that utilised three tertiary hospital sites. The target groups were physiotherapists at one intervention site and surgeons at the other intervention site, with the third hospital acting as a control site and receiving usual care. The intervention included a physiotherapy brochure and a clinical pathway for screening, to promote early identification and prompt referral of patients with a physical impairment. The primary outcome variables were screening and referral rates between sites at the study end-point. RESULTS: Logistic regression analyses were conducted on n = 174 to assess differences in screening and referral rates between sites. Patients at the intervention site that targeted physiotherapists had four times the odds of being screened for shoulder dysfunction compared to the control site (p = 0.0002), and three times the odds of being referred to physiotherapy (0.0039). There were no statistically significant differences in the odds of patients being screened for shoulder dysfunction or referred to physiotherapy at the intervention site that targeted surgeons. CONCLUSION: The translational intervention undertaken by physiotherapists resulted in significantly greater screening and referral rates of post-operative ND patients for physiotherapy.