Are our patients becoming more complex? Trends in comorbidity and functional dependence in General Medicine 2011-2019.

BACKGROUND: Anecdotally, patients don't seem to be more unwell than they were 10 years ago, yet they still seem more 'complex'. AIMS: The aim of this study was to use an objective measure to assess the trend in complexity of general medicine patients over a 9-year period. METHODS: Complexity was pragmatically defined as a composite of comorbidity plus dependence/frailty. We selected 100 consecutive patients discharged from General Medicine at Monash Medical Centre (a tertiary hospital in Melbourne, Australia) in the month of April of each year from 2011 to 2019. For each patient, we retrospectively calculated their burden of comorbidity and their degree of dependency/frailty. Comorbidity was measured using the Charlson Comorbidity Index (CCI), and dependence/frailty was assessed using the Katz Index of Independence in Activities of Daily Living (Katz ADL) and the Braden Scale (BS). The BS is a pressure injury risk assessment tool. Additional demographic data were collected, including length of stay, admission and discharge residence, 30-day readmission rate and inpatient mortality. RESULTS: There was no statistically significant change in the CCI or the Katz ADL. The median BS did however significantly decrease from 19 in 2011 to 16 in 2019 (P = 0.006), reflecting an increased risk of pressure injuries. CONCLUSIONS: Despite a stable level of comorbidity, our finding of a decreasing BS score may suggest that patients are becoming more dependent. This increase in dependency rather than a change in chronic disease burden may be the cause of apparent increasing patient complexity.

Variation in immunoglobulin use and impact on survival in myeloma.

Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real-world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia-Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow-up time of 29.5 months (interquartile range 13.3-54.3 months) were included in the analysis - 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in-situ hybridisation status, receive first-line myeloma treatment with immunomodulatory drugs or anti-CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow-up (adjusted hazard ratio 0.72, 95% CI 0.46-1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

Association between air pollution and chronic rhinosinusitis: a nested case-control study using meteorological data and national health screening cohort data.

BACKGROUND: Inconsistent results about the effect of air pollution on chronic rhinosinusitis (CRS) have been reported. This study aimed to evaluate the impact of meteorological conditions/air pollution on the prevalence of CRS in adult Koreans. METHODOLOGY: The data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 through 2015 were used. A CRS group (defined as ICD-10 codes J32, n=6159) was matched with a control group (n=24,636) in 1:4 ratios by age, sex, income, and region of residence. The meteorological conditions and air pollution data included the daily mean, highest, and lowest temperature (°C), daily temperature range (°C), relative humidity (%), ambient atmospheric pressure (hPa), sunshine duration (hr), and the rainfall (mm), SO2 (ppm), NO2 (ppm), O3 (ppm), CO (ppm), and PM10 (λg/m3) levels before the CRS diagnosis. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRS were analyzed using logistic regression analyses. RESULTS: When the NO2 level increased by 0.1 ppm, the odds for CRS increased 5.40 times, and when the CO level increased by 1 ppm and PM10 increased by 10 λg/m3, the odds for CRS decreased 0.75 times and 0.93 times, respectively. Other meteorological conditions, such as the mean/highest/lowest temperature, temperature range, rainfall and other air pollution, such as SO2 and O3, were not statistically significant. NO2 for 90 days before the index date increased the risk of CRS in all subgroups, except for the nasal polyp and older age subgroups. CONCLUSION: CRS is related to high concentrations of NO2.

Chronic rhinosinusitis and progression of cognitive impairment in dementia.

AIM: The relationship between chronic inflammatory disease and cognitive decline is still unclear, but there is increasing evidence to support the role of systemic inflammation. The aim of this study was to investigate if chronic rhinosinusitis (CRS) in dementia or mild cognitive impairment (MCI) is associated with the progression of cognitive decline. MATERIAL AND METHODS: We retrospectively reviewed the data of patients who complained of memory impairment, and underwent brain magnetic resonance imaging (MRI) from January 2006 to April 2019. According to the Mini-Mental State Examination (MMSE) score, subjects (n=661) were divided into three groups: dementia (≤17), MCI (18-23), and normal (≥24). CRS was defined as a total score of greater than or equal to 4 according to the Lund-Mackay scoring system using brain MRI. Multiple logistic regression analyses estimated adjusted odds ratio (aOR) for the association between CRS and dementia or MCI. Among the subjects with follow-up MMSE (n=286), a repeated-measures ANOVA was used to assess the difference of changes in MMSE scores between the groups with and without CRS. RESULTS: According to the initial MMSE score, there were 221 subjects with dementia, 195 with MCI, and 245 with normal results. CRS was not significantly associated with dementia (aOR=1.519, CI=0.909-2.538, P=0.111), while being suggestively associated with MCI (aOR=1.740, CI=1.041-2.906, P=0.034). The MMSE scores at follow-up decreased further in subjects with CRS than in those without CRS (P=0.009). Especially, in the initial dementia group, there was a significant between-group difference in the MMSE score from baseline to follow-up (13.6±4.3 to 11.1±6.3 in CRS group vs. 13.5±3.3 to 14.4±5.4 in no CRS group, P=0.002). CONCLUSION: The result of the present study implies a potential association between CRS and progression of cognitive decline. Physicians should be aware of this possibility in patients with clinically diagnosed CRS.

High-Intensity Physical Activity with High Serum Vitamin D Levels is Associated with a Low Prevalence of Osteopenia and Osteoporosis: A Population-Based Study.

We found that combination of high-intensity PA and high 25(OH)D levels was associated with low prevalence of osteoporosis/osteopenia. In addition, the prevalence of osteoporosis was lower in the low PA with high 25(OH)D levels than in the moderate or high PA with low 25(OH)D levels. INTRODUCTION: The aim of this study was to explore the association of physical activity (PA) and serum 25-hydroxyvitamin D (25[OH]D) levels with osteopenia/osteoporosis. METHODS: The Korean National Health and Nutrition Examination Survey data from 2008 to 2011 were used in this study. Data from 6868 individuals were selected. Each individual's level of PA was classified as 'low', 'moderate', or 'high'. Serum 25(OH)D levels were classified as 'low' or 'high'. Accordingly, the combined PA and 25(OH)D groups were divided into 6 groups. Bone mineral density (BMD) was classified as 'normal (T score ≥ - 1.0)', 'osteopenia (- 2.5 < T score < - 1.0)' or 'osteoporosis (T score ≤ - 2.5)'. Crude and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated using multinomial logistic regression models. RESULTS: The AORs (95% CIs) for osteopenia were 0.64 (0.50-0.83) in the high PA with high 25(OH)D group and 0.69 (0.53-0.88) in the moderate PA with high 25(OH)D group. The AORs (95% CIs) for osteoporosis were increased in the groups in ascending order as follows: high PA with high 25(OH)D (0.40 [0.28-0.57]) < moderate PA with high 25(OH)D (0.47 [0.33-0.66]) < low PA with high 25(OH)D (0.59 [0.42-0.83]) < high PA with low 25(OH)D (0.70 [0.49-1.00]) < moderate PA with low 25(OH)D (0.76 [0.53-1.07]) < low PA with low 25(OH)D. This result was consistent in males but not evident in females. CONCLUSION: We suggest that the combination of high-intensity PA and high 25(OH)D levels is positively associated with high BMD.

Biosorption of copper by endophytic fungi isolated from Nepenthes ampullaria.

Copper (Cu) tolerance was observed by endophytic fungi isolated from the carnivorous plant Nepenthes ampullaria (collected at an anthropogenically affected site, Kuching city; and a pristine site; Heart of Borneo). The fungal isolates, capable of tolerating Cu up to 1000 ppm (11 isolates in total), were identified through molecular method [internal transcribed spacer 4+5 (ITS4+5); ITS1+NL4; ß-tubulin region using Bt2a + Bt2b], and all of them grouped with Diaporthe, Nigrospora, and Xylaria. A Cu biosorption study was then carried out using live and dead biomass of the 11 fungal isolates. The highest biosorption capacity of using live biomass was achieved by fungal isolates Xylaria sp. NA40 (73·26 ± 1·61 mg Cu per g biomass) and Diaporthe sp. NA41 (72·65 ± 2·23 mg Cu per g biomass), NA27 (59·81 ± 1·15 mg Cu per g biomass) and NA28 (56·85 ± 4·23 mg Cu per g biomass). The fungal isolate Diaporthe sp. NA41 also achieved the highest biosorption capacity of 59·33 ± 0·15 mg g-1 using dead biomass. The living biomass possessed a better biosorption capacity than the dead biomass (P < 0·05) and the roadside fungal strains showed higher Cu biosorption capacities using live biomass compared to the jungle fungal strains (P < 0·05). SIGNIFICANCE AND IMPACT OF THE STUDY: Our study highlights that fungal biosorption capacity is highly dependent on the sampling area (roadside vs jungle) with roadside fungal strains showing significantly higher copper (Cu) biosorption capacities using living biomass compared to fungal strains originating from plants collected in virgin jungle (P < 0·05). It also highlights that different biosorption mechanisms (alive - metabolic dependent and dead biomass - metabolic independent) result in different amounts of Cu being removed from the solutions. The living biomass possessed a better biosorption capacity than the dead biomass (P < 0·05).

Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma.

Several lines of evidence have demonstrated that deregulated activation of NF-κB plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-κB upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated. In addition, we studied whether CSL can potentiate the apoptotic effect of bortezomib, a proteasome inhibitor in MM cells and in a xenograft mouse model. We found that CSL significantly reduced cell proliferation and enhanced apoptosis when used in combination with bortezomib and upregulated caspase-3 in these cells. CSL also inhibited invasion and migration of MM cells through the suppression of constitutive NF-κB activation and expression of downstream gene products such as CXCR4 and MMP-9. Moreover, CSL when administered either alone or in combination with bortezomib inhibited MM tumor growth and decreased serum IL-6 and TNF-α levels. Overall, our results suggest that CSL can abrogate MM growth both in vitro and in vivo and may serve as a useful pharmacological agent for the treatment of myeloma and other hematological malignancies.

Adaptive radiotherapy for head and neck cancers: Fact or fallacy to improve therapeutic ratio?

Modern standards of precision radiotherapy, primarily driven by the technological advances of intensity modulation and image guidance, have led to increased versatility in radiotherapy planning and delivery. The ability to shape doses around critical normal organs, while simultaneously "painting" boost doses to the tumor have translated to substantial therapeutic gains in head and neck cancer patients. Recently, dose adaptation (or adaptive radiotherapy) has been proposed as a novel concept to enhance the therapeutic ratio of head and neck radiotherapy, facilitated in part by the onset of molecular and functional imaging. These contemporary imaging techniques have enabled visualisation of the spatial molecular architecture of the tumor. Daily cone-beam imaging, besides improving treatment accuracy, offers another unique angle to explore radiomics - a novel high throughput feature extraction and selection workflow, for adapting radiotherapy based on real-time tumor changes. Here, we review the existing evidence of molecular and functional imaging in head and neck cancers, as well as the current application of adaptive radiotherapy in the treatment of this tumor type. We propose that adaptive radiotherapy can be further exploited through a systematic application of molecular and functional imaging, including radiomics, at the different phases of planning and treatment.

Belinostat exerts antitumor cytotoxicity through the ubiquitin-proteasome pathway in lung squamous cell carcinoma.

There have been advances in personalized therapy directed by molecular profiles in lung adenocarcinoma, but not in lung squamous cell carcinoma (SCC). The lack of actionable driver oncogenes in SCC has restricted the use of small-molecule inhibitors. Here, we show that SCC cell lines displayed differential sensitivities to belinostat, a pan-histone deacetylase inhibitor. Phosphoproteomic analysis of belinostat-treated SCC cells revealed significant downregulation of the MAPK pathway, along with the induction of apoptosis. In cisplatin-resistant cells that demonstrated aberrant MAPK activation, combined treatment with belinostat significantly inhibited cisplatin-induced ERK phosphorylation and exhibited strong synergistic cytotoxicity. Furthermore, belinostat transcriptionally upregulated the F-box proteins FBXO3 and FBXW10, which directly targeted son of sevenless (SOS), an upstream regulator of the MAPK pathway, for proteasome-mediated degradation. Supporting this, suppression of SOS/ERK pathway by belinostat could be abrogated by inhibiting proteasomal activity either with bortezomib or with siRNA knockdown of FBXO3/FBXW10. Taken together, these preclinical data offer a novel understanding of the epigenetic mechanism by which belinostat exerts its cytotoxicity and supports the combination with cisplatin in clinical settings for chemorefractory SCC tumors.

Physician and nurse knowledge about patient radiation exposure in the emergency department.

BACKGROUND: Imaging methods that use ionizing radiation in emergency departments (EDs) have increased with advances in radiological diagnostic methods. Physician and nurse awareness of the radiation dose in the ED and the associated cancer risks to which the patients are exposed were surveyed with a questionnaire. METHODS: A total of 191 subjects in six EDs participated in this study. ED physicians and ED nurses were asked about the risks and the radiation doses of imaging methods ordered in the ED. The differences between the two groups were compared using Student's t-test for continuous variables. A Fisher's exact and Chi-squared tests were used for categorical variables. RESULTS: A total of 82 ED physicians and 109 ED nurses completed the questionnaire; 38 (46.3%) physicians and 8 (7.3%) nurses correctly answered the question about the chest X-ray radiation dose. A question about the number of chest X-rays that is equivalent to the dose of a pelvic X-ray was answered correctly by 5 (6.1%) physicians and 9 (8.3%) nurses (P = 0.571). Questions regarding abdominal computed tomography (CT), chest CT, brain CT, abdominal ultrasonography, and brain magnetic resonance imaging were answered correctly more frequently by the physician group than the nurse group (P < 0.05). The risk of developing cancer over a lifetime due to a brain CT was correctly answered by 21 (25.6%) physicians and 30 (27.5%) nurses (P = 0.170). A similar question regarding abdominal CT was correctly answered by 21 (25.6%) physicians and 42 (38.5%) nurses (P = 0.127). CONCLUSIONS: Knowledge of the radiation exposure of radiology examinations was lower in nurses than physicians, but knowledge was poor in both groups. ED physicians and nurses should be educated about radiation exposure and cancer risks associated with various diagnostic radiological methods.

Clinical features of emergency department patients with depression who had attempted to commit suicide by poisoning.

BACKGROUND: Many patients present to the emergency department (ED) complaining of intentional poisoning. Of those, some have major depressive disorder (MDD) in their medical history. The aim of this study was to investigate the prevalence of MDD patients who were treated for poisoning in the ED. MATERIALS AND METHODS: A retrospective review was performed on 268 patients who were treated with poisoning between July 2007 and November 2011. Of these patients, we only included those who were over 18 years of age. Information regarding age, gender, cause, time of ingestion, type of drug, history of attempting suicide, and outcome, among other characteristics, was collected and compared to patients who did not have MDD. RESULTS: A total of 244 patients were included in this study. Of those, 52 patients (21.3%) had a history of MDD. Compared to non-MDD patients, a majority (34.6% vs. 19.8%) of those in the MDD group had a history of suicide attempts (P = 0.027), and 34 (65.4% in the MDD group vs. 34.4% in the non-MDD group) took more than two types of drugs (P < 0.001). There were no differences in age, sex, time of ingestion or disease severity between MDD and non-MDD patients. CONCLUSION: In poisoning patients with MDD, physicians in the ED must consider that they have a higher tendency to show suicidal behavior and to have ingested multiple types of drugs.

The clinical usefulness of initial serum procalcitonin as an aggravation predictor in a hepatobiliary tract infection at emergency department.

BACKGROUND AND OBJECTIVES: The ability to predict future clinical deterioration early in patients who present to an emergency care center with a hepatobiliary tract infection is difficult. We studied the clinical usefulness of the initial serum levels of procalcitonin in a hepatobiliary tract infection as an indicator for predicting aggravation in the early stages. METHODS: Of the patients who presented with the clinical symptoms of a hepatobiliary tract infection, 99 were diagnosed with a hepatobiliary tract infection by imaging studies and subsequently enrolled in the study. Laboratory tests were obtained in the early stage of disease after presentation to an emergency care center. We assessed and compared the serum levels of many early inflammatory markers (white blood cell [WBC] counts, C-reactive protein and procalcitonin) between patients whose symptoms were initially stable upon arrival to an emergency care center but then deteriorated to, those whose symptoms remained consistently stable. Thus, we examined if the above serum markers are useful in predicting the possibility of future symptom aggravation. RESULTS: Of a total of 99 patients, 27 were assigned to the symptom aggravation group. The serum levels of WBC counts and C-reactive protein in the aggravation group were elevated. However, the median value (interquartile range) of procalcitonin was relatively increased at 2.28 (0.41-7.84 ng/ml), demonstrating a significant difference. CONCLUSIONS: In conclusion, initial serum levels of procalcitonin might be used as an indicator for aggravation in patients with hepatobiliary tract infection at the emergency department, even though there is hemodynamic stability.

Protease-activated receptor 1 suppresses Helicobacter pylori gastritis via the inhibition of macrophage cytokine secretion and interferon regulatory factor 5.

Chronic gastritis from Helicobacter pylori infection is a major factor in the development of gastric adenocarcinoma. Factors that regulate gastritis severity are important in determining which individuals are susceptible to H. pylori-associated disease. Although protease-activated receptor 1 (PAR1) has been identified as one such host factor, its mechanism of action is unknown. Using chimeric mice, we demonstrated that PAR1-mediated protection against H. pylori gastritis requires bone marrow-derived cells. Analyses of the gastric mucosa revealed that PAR1 suppresses cellular infiltration and both T helper type 1 (Th1) and T helper type 17 (Th17) responses to infection. Moreover, PAR1 expression was associated with reduced vaccine-mediated protection against H. pylori. Analyses of H. pylori-stimulated macrophages revealed that PAR1 activation suppressed secretion of interleukin (IL)-12 and IL-23, key drivers of Th1 and Th17 immunity, respectively. Furthermore, PAR1 suppressed interferon regulatory factor 5 (IRF5), an important transcription factor for IL-12 and IL-23, both in the infected mucosa and following bacterial stimulation. PAR1 suppression of IRF5 and IL-12/23 secretion by macrophages provides a novel mechanism by which the host suppresses the mucosal Th1 and Th17 response to H. pylori infection. Dysregulation of this process is likely an important factor in the susceptibility of some individuals to H. pylori-associated disease.

Does BMI predict recurrence or complications after reoperative reflux surgery? Review of a single center's experience and a comparison of outcomes.

INTRODUCTION: Obese patients who fail primary surgical management of gastroesophageal reflux present a significant challenge. We reviewed our outcomes with reoperative reflux surgery in obese (body mass index (BMI) >30) and nonobese patients to identify predictors of failure and complications and evaluate whether reoperative fundoplication is the ideal solution for obese patients. METHODS: We conducted a retrospective review of consecutive patients undergoing reoperation for failed anti-reflux surgery between 1994 and 2013. Medical record review identified preoperative, intraoperative, and postoperative characteristics. Short- and long-term outcomes for obese and nonobese patients were compared using descriptive statistics and logistic regression. RESULTS: One hundred and nine interventions were identified in 95 patients. Clinical characteristics were similar between obese and nonobese patients. Eighty-eight (83.8%) patients underwent laparoscopic repair, 87 (79.8%) of whom had a Nissen fundoplication. Obese patients were more likely to fail via a slipped wrap (64.7 vs. 40.0%; p = 0.02). No differences were seen in short- or long-term symptomatic relief or major complications. In bivariate analysis, short-term outcomes were predicted by preoperative albumin <3.5 mg/dL (odds ratio (OR), 0.27 (confidence interval (CI), 0.08-0.96); p = 0.04) and laparoscopic conversion (OR, 0.19 (CI, 0.04-1.03); p = 0.05). Laparoscopic conversion was associated with major complications (OR, 7.33 (CI, 1.33-40.55); p = 0.02). BMI was a significant predictor for long-term outcome (p = 0.03) as a continuous variable in sensitivity analyses. CONCLUSIONS: Obese patients with recurrence after failed anti-reflux operation may be safely treated with a repeat operation. Our data indicate no difference in outcomes for patients with BMI >30, underscoring the importance of preoperative discussion as to the best approach: reoperative fundoplication or a gastric bypass.