Investigating somatic variants and pathways in mismatch repair-deficient (dMMR) colorectal carcinoma in South Africa.

AIMS: Colorectal carcinoma (CRC) is a common cause of morbidity and mortality worldwide, and an emerging public health problem in sub-Saharan Africa. Several authors have described an increased frequency of mismatch repair-deficient (dMMR) CRC in sub-Saharan Africa, but these tumours remain poorly characterised molecularly. We sought to interrogate the somatic molecular genetic landscape of dMMR CRC in a cohort of young patients to better inform Lynch syndrome (LS) screening strategies and personalised medicine approaches in our setting. METHODS: 32 patients (aged <60 years) were identified with dMMR CRC. DNA was extracted from selected formalin-fixed paraffin-embedded (FFPE) tissue resection samples and subjected to amplicon-based next-generation sequencing (NGS). RESULTS: Pathogenic or likely pathogenic variants were detected in the corresponding MMR gene in 14 of 18 (78%) MLH1/PMS2-deficient tumours, 5 of 8 (63%) MSH2/MSH6-deficient tumours, 1 of 4 (25%) tumours with isolated MSH6 loss and 0 of 2 tumours with isolated PMS2 loss. Previously unreported variants were identified in MLH1 (three) and MSH2 (one). Cases with a variant allele frequency suggesting a germline mutation were identified in MLH1 (eight), MSH2 (two) and MSH6 (one). Only one MMR gene variant was detected in more than one patient (MLH1 p.Q510*). Four POLE/POLD1 exonuclease domain variants were identified, one of which was previously unreported. CONCLUSION: The spectrum of disease-causing MMR gene variants in our population necessitates NGS testing for LS screening. This study also highlights the role of somatic testing on readily available FFPE samples to generate data on the epidemiology of CRC in different settings.

Xen-DS: a novel technique of ab externo Xen implantation augmented with a modified deep sclerectomy for surgical treatment of glaucoma.

PURPOSE: The Xen gel stent is a surgical glaucoma device which creates a subconjunctival filtering bleb, which has demonstrated good intraocular pressure (IOP) lowering and safety. Nonetheless, bleb-related problems have been reported. We present a case series of ab externo Xen procedures augmented with a deep intra-scleral lake, aiming to improve both IOP-lowering and post-operative management. METHODS: A retrospective review of 20 patients who underwent combined Xen gel stent implantation with modified deep sclerectomy at our institution from June to November 2022, with a 6-month follow-up period. We reviewed demographics, past ocular history, visual acuity (VA), IOP, visual fields, glaucoma medication use, complications, and perioperative information. RESULTS: 20 eyes of 20 patients, with a mean age of 67.45 ± 14.38 underwent surgery. Pre-operative initial IOP was 24.5 ± 7.96 mmHg, improving to 11.50 ± 2.96 mmHg at 6 months; a change of -12.89 ± 8.34 mmHg and a mean decrease of 51.13 ± 20.15% (p < 0.0001) Patients were on 3.1 ± 0.72 glaucoma medications pre-operatively, improving to 0.72 ± 1.27 at 6 months (p < 0.0001). Visual field mean deviation was -13.99 ± 9.98 dB pre-operatively and -10.27 ± 9.06 dB at 6 months, with VA of 0.287 ± 0.69 pre-operatively and 0.31 ± 0.76 LogMAR post-operatively. No patients required bleb needling. 2 patients underwent subsequent bleb revision surgery. 2 patients developed choroidal effusions, which were managed conservatively with good visual outcomes. CONCLUSION: In this preliminary study, we have found the modification of Xen gel stent implant surgery with a modified deep sclerectomy to offer good IOP lowering, with low rates of bleb needling and a good safety profile.

Factors Associated with Health-Related Quality of Life Among Breast Cancer Survivors in Saudi Arabia: Cross-Sectional Study.

BACKGROUND: Assessment of health-related quality of life (HRQOL) is a major concern among breast cancer survivors. Little is known about HRQO and its determinants in Saudi women with breast cancer (BC). This study aimed to describe the HRQOL of Saudi women with breast cancer and the association between HRQO and sociodemographic and clinical variables. METHODS: This cross-sectional study involved 147 BC participants who completed the 36-item Short Form Health Survey (SF-36). Multivariable linear logistic regression analysis was conducted to determine factors associated with HRQOL. RESULTS: For the physical component scale, general health scored the highest (55.41±17.99) while, role physical function scored the lowest (48.61±22.51). The mean scores in the mental component were higher for social function (56.91±20.84), while the lowest score was observed for energy and vitality (49.62±20.84). Significant differences were observed in many SF-36 domains across the sociodemographic and clinical variables. Older age, having had a mastectomy as well as comorbid conditions, and receiving chemotherapy and hormonal therapy were associated with decreased HRQOL. However, being physically active, employed, and having more education were associated with higher HRQOL. CONCLUSION: HRQOL is generally poor among breast cancer survivors in Saudi Arabia, depending on a variety of factors. These findings highlight the need for routine QOL assessment. Furthermore, recognizing these predictors may play a key role in maximizing HRQOL for breast cancer participants.

An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells.

BACKGROUND: Ultrasound-responsive microbubbles offer a means of achieving minimally invasive, localised drug delivery in applications including regenerative medicine. To facilitate their use, however, it is important to determine any cytotoxic effects they or their constituents may have. The aim of this study was to test the hypothesis that phospholipid-shelled microbubbles are non-toxic to human bone-derived cells at biologically-relevant concentrations. METHODS: Microbubbles were fabricated using combinations of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC), polyoxyethylene(40) stearate (PEG40S) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene-glycol)-2000] (DSPE-PEG2000). Microbubble size and concentration were measured as a function of time and temperature by optical microscopy. Effects on MG63 osteosarcoma and human bone marrow stromal cells (BMSCs) were measured for up to 72 h by assay for viability, metabolic activity and proliferation. RESULTS: DBPC:DSPE-PEG2000 microbubbles were significantly more stable than DSPC:PEG40S microbubbles under all conditions tested. Serum-containing medium had no detrimental effect on microbubble stability, but storage at 37 °C compared to at 4 °C reduced stability for both preparations, with almost complete dissolution of microbubbles at times ≥24 h. DSPC:PEG40S microbubbles had greater inhibitory effects on cell metabolism and growth than DBPC:DSPE-PEG2000 microbubbles, with PEG40S found to be the principle inhibitory component. These effects were only evident at high microbubble concentrations (≥20% (v/v)) or with prolonged culture (≥24 h). Increasing cell-microbubble contact by inversion culture in a custom-built device had no inhibitory effect on metabolism. CONCLUSIONS: These data indicate that, over a broad range of concentrations and incubation times, DBPC:DSPE-PEG2000 and DSPC:PEG40S microbubbles have little effect on osteoblastic cell viability and growth, and that PEG40S is the principle inhibitory component in the formulations investigated.

Long-term health-related quality of life and independence among older survivors of serious injury.

BACKGROUND: Little is known about the recovery experiences of older trauma intensive care unit (TICU) survivors and the relationship between geriatric trauma care and long-term functional ability and health-related quality of life (HRQOL). METHODS: We conducted a prospective cohort study of 218 patients (age, ≥65 years) admitted to a Level 1 regional trauma center TICU before versus after implementation of a geriatric care bundle with protocolized geriatrics consultations (Geri-T). Survivors or their proxies were interviewed approximately 1 year after hospitalization. Outcomes included the Katz Index of Independence in Activities of Daily Living (ADLs), Lawton Instrumental Activities of Daily Living (IADLs), and EQ-5D-5L HRQOL survey. Two investigator-developed questions regarding recovery experiences were included. Differences in outcomes among survivors admitted before versus after Geri-T were analyzed using multivariable linear regression. Responses to questions about recovery experiences were qualitatively assessed using content analysis. RESULTS: We reached 67% (146/218) of hospital survivors or their proxies across both groups; 126 patients were still alive and completed the survey. Mean age was 76 (SD, 8), 36% were female, and 90% were independent with ADLs preinjury. At follow-up, independence with ADLs was 76% and IADLs was 63%. The mean EQ-5D-5L index score was 0.78 (SD, 0.18). Most patients (65%) reported having not returned to preinjury functional status. Neither functional ability or HRQOL differed significantly among patients admitted before versus after Geri-T. Content analysis of open-ended questions revealed themes of activity limitations, persistent pain, and cognitive dysfunction. CONCLUSION: Nearly one-fifth of TICU survivors experienced loss of ADL function 1 year after injury, and most reported having not returned to preinjury functional status. Nonetheless, patient-reported HRQOL was comparable to age-adjusted norms. Geri-T was not associated with differences in HRQOL or functional ability. Survivors reported persistent difficulty with activities beyond those of daily living, pain, and cognition. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level III.

Four cases of acute comitant esotropia associated with diffuse intrinsic pontine glioma in children.

BACKGROUND: Acute acquired concomitant esotropia (AACE) is usually a benign form of strabismus that infrequently is associated with intracranial pathology. Clinicians have noted an increase in its incidence and theorize that it may be related to public health "lockdown" measures taken in response to the COVID-19 pandemic. With an increased incidence of AACE clinicians must firstly differentiate AACE from common accommodative esotropia and secondly recognize AACE as a possible sign of serious neuropathology.Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating diagnosis for affected families. Children typically present at age 6-7 years with cranial nerve palsies, long tract signs, and/or cerebellar signs. Diagnosis is made from characteristic findings on magnetic resonance brain imaging (MRI brain) and treatment includes radiotherapy and palliative care. Two years from diagnosis, 90% of affected children will have died from their disease. CASE SERIES: We present four cases that attended our pediatric ophthalmology clinic with AACE either as a presenting sign of DIPG or as a clinical finding following a DIPG diagnosis. Patient A (age 5 years) presented to the emergency eye clinic with sudden onset diplopia and intermittent esotropia. Suppression later developed, they had 0.00 logMAR visual acuity either eye, and bilateral physiological hypermetropia. MRI brain imaging requested as a result of the unusual presentation led to the DIPG diagnosis. The other 3 cases (ages 11, 5 & 5 years) were assessed post DIPG diagnosis and found to have an esotropia measuring bigger on 1/3-meter fixation than 6-meter fixation, full ocular motility, physiological hypermetropia or emmetropia, and visual acuity normal for age. Other than patient B (age 11 years), who had papilledema and gaze evoked nystagmus when they were assessed 2 weeks prior to death, no patient had any other clinical eye findings. CONCLUSIONS: This small series of 4 patients attending our clinic within a 12-month period supports the notion that children presenting with AACE should routinely be offered brain MRI. Not all children with DIPG-associated AACE have significant ophthalmic findings indicative of intracranial pathology. With the potential for increased incidence of AACE related to lockdowns, clinicians should be reminded of the infrequent possibility their patient has a more serious condition.

Perspectives on recovery from older adult trauma survivors living in rural areas.

Background: Older patients living in rural areas face unique challenges after trauma that may hinder optimal recovery. This study aims to qualitatively assess postdischarge challenges in this vulnerable population. Methods: We conducted remote interviews with older trauma survivors in Washington State previously hospitalized in 2019 and residing in rural areas as determined by rural-urban commuting area code. Participants were identified through our institution's trauma registry and linked with postdischarge data. All eligible participants were contacted. Interview questions focused on needs relating to discharge transition, medical needs, housing, and daily living. Transcribed interviews underwent content analysis to derive a code hierarchy and themes. Results: We conducted 18 interviews out of 83 survivors queried. Compared with non-participants, interviewees had a higher rate of secondary insurance (61% vs 34%), and fewer had an emergency department visit within 1 year (22% vs 34%). Content analysis yielded four major themes: discharge transitions, loss of control, rural insights, and self-efficacy. Most patients felt prepared for discharge and had social support. Regardless of disposition type, most patients needed therapy sessions after discharge. Geography and transportation issues were among the biggest barriers. Most participants were never offered a telemedicine appointment but would have used it if offered. Subthemes of self-efficacy included financial security, leisure, personal outlook, physical and logistical resources, and participants' support systems. Discussion: Older trauma patients from rural areas face unique challenges after discharge. Key strategies to improve patient experience might include more telemedicine appointments and increased awareness of resources in rural communities. Level of evidence: III.

Liver Fibrosis Marker and Postoperative Mortality in Patients Without Overt Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can progress to advanced fibrosis, which, in the nonsurgical population, is associated with poor hepatic and extrahepatic outcomes. Despite its high prevalence, NAFLD and related liver fibrosis may be overlooked during the preoperative evaluation, and the role of liver fibrosis as an independent risk factor for surgical-related mortality has yet to be tested. The aim of this study was to assess whether fibrosis-4 (FIB-4), which consists of age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelets, a validated marker of liver fibrosis, is associated with postoperative mortality in the general surgical population. METHODS: A historical cohort of patients undergoing general anesthesia at an academic medical center between 2014 and 2018 was analyzed. Exclusion criteria included known liver disease, acute liver disease or hepatic failure, and alcohol use disorder. FIB-4 score was categorized into 3 validated predefined categories: FIB-4 ≤1.3, ruling out advanced fibrosis; >1.3 and <2.67, inconclusive; and ≥2.67, suggesting advanced fibrosis. The primary analytic method was propensity score matching (FIB-4 was dichotomized to indicate advanced fibrosis), and a secondary analysis included a multivariable logistic regression. RESULTS: Of 19,861 included subjects, 1995 (10%) had advanced fibrosis per FIB-4 criteria. Mortality occurred intraoperatively in 15 patients (0.1%), during hospitalization in 272 patients (1.4%), and within 30 days of surgery in 417 patients (2.1%). FIB-4 ≥2.67 was associated with increased intraoperative mortality (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.25-10.58), mortality during hospitalization (OR, 3.14; 95% CI, 2.37-4.16), and within 30 days from surgery (OR, 2.46; 95% CI, 1.95-3.10), after adjusting for other risk factors. FIB-4 was related to increased mortality in a dose-dependent manner for the 3 FIB-4 categories ≤1.3 (reference), >1.3 and <2.67, and ≥2.67, respectively; during hospitalization (OR, 1.89; 95% CI, 1.34-2.65 and OR, 4.70; 95% CI, 3.27-6.76) and within 30 days from surgery (OR, 1.77; 95% CI, 1.36-2.31 and OR, 3.55; 95% CI, 2.65-4.77). In a 1:1 propensity-matched sample (N = 1994 per group), the differences in mortality remained. Comparing the FIB-4 ≥2.67 versus the FIB-4 <2.67 groups, respectively, mortality during hospitalization was 5.1% vs 2.2% (OR, 2.70; 95% CI, 1.81-4.02), and 30-day mortality was 6.6% vs 3.4% (OR, 2.26; 95% CI, 1.62-3.14). CONCLUSIONS: A simple liver fibrosis marker is strongly associated with perioperative mortality in a population without apparent liver disease, and may aid in future surgical risk stratification and preoperative optimization.

Frailty status as a potential factor in increased postoperative opioid use in older adults.

BACKGROUND: Prescription opioids are commonly used for postoperative pain relief in older adults, but have the potential for misuse. Both opioid side effects and uncontrolled pain have detrimental impacts. Frailty syndrome (reduced reserve in response to stressors), pain, and chronic opioid consumption are all complex phenomena that impair function, nutrition, psychologic well-being, and increase mortality, but links among these conditions in the acute postoperative setting have not been described. This study seeks to understand the relationship between frailty and patterns of postoperative opioid consumption in older adults. METHODS: Patients ≥ 65 years undergoing elective surgery with a planned hospital stay of at least one postoperative day were recruited for this cohort study at pre-anesthesia clinic visits. Preoperatively, frailty was assessed by Edmonton Frailty and Clinical Frailty Scales, pain was assessed by Visual Analog and Pain Catastrophizing Scales, and opioid consumption was recorded. On the day of surgery and subsequent hospitalization days, average pain ratings and total opioid consumption were recorded daily. Seven days after hospital discharge, patients were interviewed using uniform questionnaires to measure opioid prescription use and pain rating. RESULTS: One hundred seventeen patients (age 73.0 (IQR 67.0, 77.0), 64 % male), were evaluated preoperatively and 90 completed one-week post discharge follow-up. Preoperatively, patients with frailty were more likely than patients without frailty to use opioids (46.2 % vs. 20.9 %, p = 0.01). Doses of opioids prescribed at hospital discharge and the prescribed morphine milligram equivalents (MME) at discharge did not differ between groups. Seven days after discharge, the cumulative MME used were similar between cohorts. However, patients with frailty used a larger fraction of opioids prescribed to them (96.7 % (31.3, 100.0) vs. 25.0 % (0.0, 83.3), p = 0.007) and were more likely (OR 3.7, 95 % CI 1.13-12.13) to use 50 % and greater of opioids prescribed to them. Patients with frailty had higher pain scores before surgery and seven days after discharge compared to patients without frailty. CONCLUSIONS: Patterns of postoperative opioid use after discharge were different between patients with and without frailty. Patients with frailty tended to use almost all the opioids prescribed while patients without frailty tended to use almost none of the opioids prescribed.

High rates of tenofovir failure in a CRF01_AE-predominant HIV epidemic in the Philippines.

BACKGROUND: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. This increase was accompanied by a shift in the predominant HIV subtype from B to CRF01_AE. Increasing evidence points to a difference in treatment responses between subtypes. We examined treatment failure and acquired drug resistance (ADR) in people living with HIV (PLHIVs) after one year on antiretrovirals (ARVs). METHODS: PLHIV maintained on ARVs for one year were recruited. Treatment failure was defined as a viral load of ≥1000 copies/mL. Sanger sequencing for genotyping and drug resistance mutation (DRM) detection was performed on patients failing treatment. RESULTS: 513 PLHIV were enrolled. The most common antiretroviral regimens were TDF+3TC + EFV (269) and AZT+3TC + EFV (155). 53 (10.3%) subjects failed treatment. Among these, 48 (90.6%) had DRMs, 84.9% were subtype CRF01_AE. Tenofovir-based regimens performed worse than zidovudine-based regimens (OR 3.28, 95% CI 1.58-7.52 p < 0.001). Higher rates of NRTI, NNRTI, K65R tenofovir resistance, and multi-class resistance were found compared to those reported in literature. CONCLUSIONS: HIV treatment failure at one year of treatment in the Philippines is 10.3%. We found unusually high tenofovir and multiclass resistance, and optimal ARV regimens may need to be reevaluated for CRF01_AE-predominant epidemics.

[Procedure-specific postoperative gastrointestinal hemorrhage]. / Verfahrensspezifische postoperative gastrointestinale Blutungen.

Gastrointestinal bleeding (GIB) can occur as a complicating issue in the postoperative course after visceral surgery. It can be of varying clinical extent ranging from mild anemia to fatal hemorrhagic shock. Symptomatic manifestations of a GIB are hematemesis, melena and hematochezia. The GIB are fundamentally differentiated into upper and lower GIB. While upper GIB is defined as the occurrence of endoluminal hemorrhage above the ligament of Treitz, correspondingly the definition of lower GIB is intraluminal bleeding distal to the duodenojejunal flexure. Knowledge of their procedure-related incidence during the postoperative course enables a better assessment of the necessary intervention.

Frailty assessment: from clinical to radiological tools.

Frailty is a syndrome of cumulative decline across multiple physiological systems, which predisposes vulnerable adults to adverse events. Assessing vulnerable patients can potentially lead to interventions that improve surgical outcomes. Anaesthesiologists who care for older patients can identify frailty to improve preoperative risk stratification and subsequent perioperative planning. Numerous clinical tools to diagnose frailty exist, but none has emerged as the standard tool to be used in clinical practice. Radiological modalities, such as computed tomography and ultrasonography, are widely performed before surgery, and are therefore available to be used opportunistically to objectively evaluate surrogate markers of frailty. This review presents the importance of frailty assessment by anaesthesiologists; lists common clinical tools that have been applied; and proposes that utilising radiological imaging as an objective surrogate measure of frailty is a novel, expanding approach for which anaesthesiologists can significantly contribute to broad implementation.

Association of Brain Atrophy and Masseter Sarcopenia With 1-Year Mortality in Older Trauma Patients.

Importance: Older adults are disproportionately affected by trauma and accounted for 47% of trauma fatalities in 2016. In many populations and disease processes, described risk factors for poor clinical outcomes include sarcopenia and brain atrophy, but these remain to be fully characterized in older trauma patients. Sarcopenia and brain atrophy may be opportunistically evaluated via head computed tomography, which is often performed during the initial trauma evaluation. Objective: To investigate the association of masseter sarcopenia and brain atrophy with 1-year mortality among trauma patients older than 65 years by using opportunistic computed tomography imaging. Design, Setting, and Participants: This retrospective cohort study was conducted in a level 1 trauma center from January 1, 2011, to December 31, 2014, with a 1-year follow-up to assess mortality. Washington state residents 65 years or older who were admitted to the trauma intensive care unit with a head Abbreviated Injury Scale score of less than 3 were eligible. Patients with incomplete data and death within 1 day of admission were excluded. Data analysis was completed from June 2017 to October 2018. Exposures: Masseter muscle cross-sectional area and brain atrophy index were measured using a standard clinical Picture Archiving and Communication System application to assess for sarcopenia and brain atrophy, respectively. Main Outcomes and Measures: Primary outcome was 1-year mortality. Secondary outcomes were discharge disposition and 30-day mortality. Results: The study cohort included 327 patients; 72 (22.0%) had sarcopenia only, 71 (21.7%) had brain atrophy only, 92 (28.1%) had both, and 92 (28.1%) had neither. The mean (SD) age was 77.8 (8.6) years, and 159 patients (48.6%) were women. After adjustment for age, comorbidity, complications, and injury characteristics, masseter sarcopenia and brain atrophy were both independently and cumulatively associated with mortality (masseter muscle cross-sectional area per SD less than the mean: hazard ratio, 2.0 [95% CI, 1.2-3.1]; P = .005; brain atrophy index per SD greater than the mean: hazard ratio, 2.0 [95% CI, 1.1-3.5]; P = .02). Conclusions and Relevance: Masseter muscle sarcopenia and brain atrophy were independently and cumulatively associated with 1-year mortality in older trauma patients after adjustment for other clinical factors. These radiologic indicators are easily measured opportunistically through standard imaging software. The results can potentially guide conversations regarding prognosis and interventions with patients and their families.

Trauma Providers' Perceptions of Frailty Assessment: A Mixed-Methods Analysis of Knowledge, Attitudes, and Beliefs.

OBJECTIVES: Quality improvement in geriatric trauma depends on timely identification of frailty, yet little is known about providers' knowledge and beliefs about frailty assessment. This study sought to understand trauma providers' understanding, beliefs, and practices for frailty assessment. METHODS: We developed a 20-question survey using the Health Belief Model of health behavior and surveyed physicians, advanced practice providers, and trainees on the trauma services at a single institution that does not use formal frailty screening of all injured seniors. Results were analyzed via mixed methods. RESULTS: One hundred fifty-one providers completed the survey (response rate 92%). Respondents commonly included calendar age as an integral factor in their determinations of frailty but also included a variety of other factors, highlighting limited definitional consensus. Respondents perceived frailty as important to older adult patient outcomes, but assessment techniques were varied because only 24/151 respondents (16%) were familiar with current formal frailty assessment tools. Perceived barriers to performing a formal frailty screening on all injured older adults included the burdensome nature of assessment tools, insufficient training, and lack of time. When prompted for solutions, 20% of respondents recommended automation of the screening process by trained, dedicated team members. CONCLUSIONS: Providers seem to recognize the impact that a diagnosis of frailty has on outcomes, but most lack a working knowledge of how to assess for frailty syndrome. Some providers recommended screening by designated, formally trained personnel who could notify decision makers of a positive screen result.

Patterns of helminth infections in Rattus rattus and Mus musculus from two Mayan communities in Mexico.

The black rat Rattus rattus and the house mouse Mus musculus are two commensal rodent species that harbour and shed zoonotic pathogens, including helminths. The aim of this survey was to study the helminth community and the patterns of infections in R. rattus and M. musculus from two Mayan communities in Mexico. Gastrointestinal helminths were isolated from 322 M. musculus and 124 R. rattus, including Gongylonema neoplasticum, Hassalstrongylus aduncus, Hassalstrongylus musculi, Hydatigera taeniaeformis metacestode, Hymenolepis diminuta, Nippostrongylus brasiliensis, Oligacanthorhynchidae gen. sp., Syphacia muris, Syphacia obvelata, Rodentolepis microstoma and Trichuris muris. The overall richness of helminths was seven in R. rattus and six in M. musculus. The results of generalized linear models showed that juvenile rodents had lower probabilities of being infected with G. neoplasticum, H. taeniaeformis and H. musculi than adult rodents. A positive association between the prevalence of S. muris and rat abundance was found. The intensity of infection with S. muris was higher in the rainy season than in the dry season; the opposite result was found for H. musculi infection. Male R. rattus harboured more S. muris specimens. The intensity of infection with T. muris was inversely associated with mouse abundance. The presence of the zoonotic H. diminuta, as well as H. taeniaeformis and R. microstoma in rodent populations indicates that there is risk of transmission, and that their entire life cycle occurs in the study area.

Complications in low-risk older adult trauma patients: A case-control study.

BACKGROUND: Although some geriatric trauma patients may be at low risk of complications, poor outcomes are pronounced if complications do occur. Prevention in this group decreases the risk of excess morbidity and mortality. METHODS: We performed a case-control study of trauma patients 65 years or older treated from January 2015 to August 2016 at a Level I trauma center with a Trauma Quality Improvement Program-predicted probability of complication of less than 20%. Cases had one of the following complications: unplanned admission to the intensive care unit (ICU), unplanned intubation, pneumonia, or unplanned return to the operating room. Two age-matched controls were randomly selected for each case. We collected information on comorbidities, home medications, and early medical care and calculated odds ratios using multivariable conditional logistic regression. RESULTS: Ninety-four patients experienced unplanned admission to ICU (n = 51), unplanned intubation (n = 14), pneumonia (n = 21), and unplanned return to the operating room (n = 8). The 188 controls were more frequently intubated and had higher median ISS but were otherwise similar to cases. The adjusted odds of complication were higher for patients on a home ß-blocker (adjusted odds ratio [aOR], 2.2; 95% confidence interval [CI], 1.2-4.0) and home anticoagulation (aOR, 2.2; 95% CI, 1.2-4.1). Patients with diabetes (aOR 2.0; 95% CI, 1.1-3.7) and dementia (aOR, 2.0; 95% CI, 1.0-4.3) also had higher odds of complication. The adjusted odds of complication for patients receiving geriatrics consultation was 0.4 (95% CI, 0.2-1.0; p = 0.05). Pain service consultation and indwelling pain catheter placement may be protective, but CIs included 1. There was no association between opiates, benzodiazepines, fluid administration, or blood products in the first 24 hours and odds of complication. CONCLUSIONS: Geriatrics consultation was associated with lower odds of unplanned admission to the ICU, unplanned intubation, pneumonia, and unplanned return to the operating room in low-risk older adult trauma patients. Pathways that support expanding comanagement strategies with geriatricians are needed. LEVEL OF EVIDENCE: Therapeutic/Care management, Level IV.

The Aged Microenvironment Influences the Tumorigenic Potential of Malignant Prostate Epithelial Cells.

The incidence of prostate cancer is directly linked to age, but age-associated changes that facilitate prostate cancer development and progression are poorly understood. This study investigated age-related changes in the prostate microenvironment for their influence on prostate cancer behavior. Prostate cancer cells implanted orthotopically into the prostate demonstrated accelerated tumor growth in aged compared with young mice. Metastatic lesions following intravenous injection were also more numerous in aged mice. Tumors from young and aged mice showed no significant differences concerning their proliferation index, apoptosis, or angiogenesis. However, analysis of tumor-infiltrating immune cells by IHC and RNA sequencing (RNA-seq) revealed elevated numbers of macrophages in prostates from aged mice, which are quickly polarized towards a phenotype resembling protumorigenic tumor-associated macrophages upon tumor cell engraftment. Older patients with prostate cancer (>60 years old) in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset displayed higher expression of macrophage markers (CD163 and VSIG4) which associated with higher rates of biochemical relapse. Remodeling of the collagenous extracellular matrix (ECM) was associated with prostate cancer growth and invasion in the aged microenvironment. Moreover, the collagen matrix extracted from aged mice enhanced the invasiveness and proliferation of prostate cancer cells in vitro. Together, these results demonstrate that the aged prostatic microenvironment can regulate the growth and metastasis of malignant prostate cells, highlighting the role of resident macrophages and their polarization towards a protumorigenic phenotype, along with remodeling of the ECM. IMPLICATIONS: These findings demonstrate the importance of age-associated tumor microenvironment alterations in regulating key aspects of prostate cancer progression.

Utility of Geriatric Assessment in the Projection of Early Mortality Following Hip Fracture in the Elderly Patients.

Hip fractures result in significant morbidity and mortality in elders. Indicators of frailty are associated with poor outcomes. Commonly used frailty tools rely on motor skills that cannot be performed by this population. We determined the association between the Charlson Comorbidity Score (CCS), intraoperative hypotension (IOH), and a geriatric medicine consult index (GCI) with short-term mortality in hip fracture patients. A retrospective cohort study was conducted at a single institution over a 2-year period. Patients aged 65 years and older who sustained a hip fracture following a low-energy mechanism were identified using billing records and our orthopedic fracture registry. Medical records were reviewed to collect demographic data, fracture classification and operative records, calculation of CCS, intraoperative details including hypotension, and assessments recorded in the geriatric consult notes. The GCI was calculated using 30 dichotomous variables contained within the geriatric consult note. The index, ranging from 0 to 1, included markers for physical and cognitive function, as well as medications. A higher GCI score indicated more markers for frailty. One hundred eight patients met inclusion criteria. Sixty-four (59%) were females and the average age was 77.3 years. Thirty-five (32%) patients sustained femoral neck fractures, and 73 (68%) patients sustained inter-/pertrochanteric hip fractures. The 30-day mortality was 6%; the 90-day mortality was 13%. The mean GCI was 0.30 in the 30-day survivor group as compared to 0.52 in those who died. The mean GCI was 0.28 in patients who were alive at 90 days as compared to 0.46 in those who died. In contrast, the CCS and IOH were not associated with 30- or 90-day mortality. In our older hip fracture patients, an index calculated from information routinely obtained in the geriatric consult evaluation was associated with 30- and 90-day mortality, whereas the CCS and measures of IOH were not.

Bones heal, teeth don't! The involvement of dentists in the acute and long-term management of patients injured in the Manchester Arena Bomb.

This paper outlines the involvement of dentists in the treatment of patients following the terror attack at Manchester Arena on 22 May 2017. It predominantly describes the role of the authors - a paediatric dental consultant and maxillofacial surgery dental core trainee (DCT). As a result of the incident a number of patients suffered oro-facial injuries, with many treated at Central Manchester Foundation Trust Hospitals' Manchester Royal Infirmary and Royal Manchester Children's Hospital. The major incident response of the trust is discussed, as are the presentation of blast injuries and corresponding NHS guidance. Two paediatric cases present the role of the paediatric dental consultant in the acute, intermediate and long-term management of these patients. The presentation of unique dento-alveolar injuries in the context of other trauma and their subsequent treatment demanded true multidisciplinary management. The importance of teeth and oral health to physical and psycho-social wellbeing and recovery was clear and recognised by other teams involved in the patients' management. The experience reinforced the overall impact dental health has on physical and psycho-social health, and how a holistic approach is integral to treatment of major trauma.