Pleural Effusion Outcomes in Intensive Care: Analysis of a Large Clinical Database.

BACKGROUND: Pleural effusions are common in critically ill patients. However, the management of pleural fluid on relevant clinical outcomes is poorly studied. We evaluated the impact of pleural effusion in the intensive care unit (ICU). METHODS: A large observational ICU database Multiparameter Intelligent Monitoring in Intensive Care III was utilized. Analyses used matched patients with the same admission diagnosis, age, gender, and disease severity. RESULTS: Of 50 765, 3897 (7.7%) of critically ill adult patients had pleural effusions. Compared to patients without effusion, patients with effusion had higher in-hospital (38.7% vs 31.3%, P < .0001), 1-month (43.1% vs 36.1%, P < .0001), 6-month (63.6% vs 55.7%, P < .0001), and 1-year mortality (73.8% vs 66.1%, P < .0001), as well as increased length of hospital stay (17.6 vs 12.7 days, P < .0001), ICU stay (7.3 vs 5.1 days, P < .0001), need for mechanical ventilation (63.1% vs 55.7%, P < .0001), and duration of mechanical ventilation (8.7 vs 6.3 days, P < .0001). A total of 1503 patients (38.6%) underwent pleural fluid drainage. Patients in the drainage group had higher in-hospital (43.9% vs 35.4%, P = .0002), 1-month (47.7% vs 39.7%, P = .0005), 6-month (67.1% vs 61.8%, P = .0161), and 1-year mortality (77.1% vs 72.1%, P = .0147), as well as increased lengths of hospital stay (22.1 vs 16.0 days, P < .0001), ICU stay (9.2d vs 6.4 days, P < .0001), and duration of mechanical ventilation (11.7 vs 7.1 days, P < .0001). CONCLUSIONS: The presence of a pleural effusion was associated with increased mortality in critically ill patients regardless of disease severity. Drainage of pleural effusion was associated with worse outcomes in a large, heterogeneous cohort of ICU patients.

HDAC8 inhibition ameliorates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease, and fibroblast-myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase-8 (HDAC8) has been shown to associate with α-smooth muscle actin (α-SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been reported. This study investigated the role of HDAC8 in pulmonary fibrosis with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as transforming growth factor (TGF)ß1-treated normal human lung fibroblasts (NHLFs). Immunoprecipitation experiments revealed that HDAC8 was associated with α-SMA in TGFß1-treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8-selective inhibitor) repressed TGFß1-induced fibroblast contraction and α-SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGFß1-induced expression of profibrotic molecules such as fibronectin and increased expression of antifibrotic molecules such as peroxisome proliferator-activated receptor-γ (PPARγ). Chromatin immunoprecipitation quantitative PCR using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGFß1-induced loss of H3K27ac at the PPARγ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as expression of type 1 collagen and fibronectin in bleomycin-treated mouse lungs. These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases.

The clinical application of incisional negative pressure wound therapy in severe subcutaneous emphysema: A case series.

Severe subcutaneous emphysema (SSE) is the presence of a high-volume accumulation of air in the subcutaneous tissue caused by traumatic injuries, infections, iatrogenic causes, or can also manifest spontaneously. A variety of techniques have been reported, with varying levels of success. We present a multicenter case series detailing four patients who developed SSE and were treated with Incisional Negative Pressure Wound Therapy (INPWT). All patients significantly improved with the INPWT treatment within 6 to 48 h. Our experience suggests INPWT is a valuable procedure available for treating SSE and recommend prospective randomized studies be conducted to determine targeted patient selection and clinical application of INPWT among the SSE patient population.

The economic impact of tobacco smoking and secondhand smoke exposure in Jordan: estimating the direct and indirect costs.

AIM: To quantify the economic burden associated with tobacco smoking among smokers aged 30-69 years, and second-hand smokers (SHS) aged 15-69 years in Jordan. MATERIALS AND METHODS: A prevalence-based analysis was conducted in alignment with the Economics of Tobacco Toolkit developed by the WHO. The time-horizon of the analysis was one year (2019). Direct and indirect costs were estimated using data from the 2019 Global Burden of Diseases study. The analysis targeted the Jordanian population of smokers aged 30-69 years, and SHS aged 15-69 years. Adjustments were applied for age, gender, and smoking-related diseases. Direct costs were estimated using the smoking-attributable fraction (SAF) and national health expenditures. Indirect costs were divided into morbidity and mortality components. A discount rate of 3.0% and an annual productivity growth rate of 1.0% were assumed in modelling future economic losses. A sensitivity analysis was conducted on the lower and upper estimates of data used in this study. RESULTS: The cost of tobacco smoking and SHS exposure was estimated at US$2,108 million (95% confidence interval [CI] = US$2,003 million-US$2,245 million). This represents 4.7% (95%CI = 4.5%-5.0%) of national gross domestic product (GDP). Direct costs accounted for 3.1% of national GDP. Tobacco smoking accounted for 85.0% of total cost and SHS exposure accounted for 15.0% of total cost. Direct costs accounted for 67.0% of total cost, while indirect morbidity and mortality costs accounted for 9.0% and 24.0% of total cost, respectively. Non-communicable diseases accounted for 96.0% of total direct costs compared to communicable diseases (4.0% of total direct costs). CONCLUSIONS: Smoking cessation interventions such as raising taxes on cigarettes, protecting people from tobacco smoke, warning labels, plain packaging, and bans on advertising, are crucial for controlling national expenditures for treating smoking-related diseases and for averting future economic losses.

In this work, we aimed to calculate the annual economic impact of tobacco smoking in Jordan in 2019. We used the World Health Organization toolkit methodology to estimate both the direct and indirect costs associated with smoking nationally. Our focus was on Jordanian smokers aged 30-69 years and people exposed to second-hand smoke aged 15­69 years. Direct costs were calculated using epidemiological data on the proportion of health expenditures attributable to smoking and the national health expenditures. Indirect costs were divided into two components: morbidity and mortality. We also projected future economic losses, assuming a 3.0% discount rate and a 1.0% annual growth rate of productivity. Our study estimated that the cost of smoking and exposure to second-hand smoke was US$2,108 million (US$2,003 million-US$2,245 million), which accounted for 4.7% (4.5%-5.0) of Jordan's gross domestic product. The majority of the cost (85.0%) was due to direct smoking, while 15.0% was due to exposure to second-hand smoke. Direct costs made up 67.0% of the total cost, while the costs related to morbidity and mortality accounted for 9.0% and 24.0% of the total cost, respectively. In conclusion, our study emphasized that tobacco smoking has a significant economic impact on Jordan. Therefore, it is crucial to implement effective smoking cessation programs, such as enforcing existing anti-tobacco policies and raising taxes. These measures can help control national expenditures for treating smoking-related diseases and prevent future economic losses.

Clinical, molecular, and drug resistance epidemiology of HIV in Jordan, 2019-2021: A national study.

BACKGROUND: Limited epidemiologic studies have been conducted in Jordan describing the HIV epidemic. This study aimed to address this gap to inform HIV prevention and control. METHODS: A nationally-representative cross-sectional study was conducted among adults living with HIV in Jordan. Laboratory testing included HIV viral load and next-generation-sequencing-based clinical genotype. Log-binomial regression estimated risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Among 231 (70%) participants, most were male (184/80%), and from Jordan (217/94%). Among 188 treatment-experienced-participants (>6 months), 165 (88%) were virally suppressed. High-level resistance was most frequent against nucleoside reverse transcriptase inhibitor (13/81%), and integrase-strand transfer inhibitor (INSTI) (10/62%) drugs among viremic (≥1000 HIV copies/mL) treatment-experienced participants with drug-resistant mutations (DRMs, n = 16). Common HIV subtypes (n = 43) were B (6/14%), A1 (5/12%), and CRF01_AE (5/12%); additionally, novel recombinant forms were detected. In multivariate analysis, independently higher risk for late diagnosis (n = 49) was observed with diagnosis through blood donation (vs check-up: RR 2.20, 95%CI 1.16-4.17) and earlier time-period of diagnosis (1986-2014 vs 2015-2021: RR 2.87, 95%CI 1.46-5.62). CONCLUSIONS: Late diagnosis and INSTI resistance endanger national HIV prevention and treatment in Jordan-high-level resistance to INSTI suggests therapeutic drug monitoring is needed for treatment efficacy and conservation of treatment options.

Salvaging the Digit in Invasive Subungual Malignancies Using a Triple Technique under Awake Local Anesthesia.

INTRODUCTION: Amputation for subungual malignancy (SUM) was thought to be the gold standard in preventing recurrence and metastasis. The rationale behind this aggressive treatment was never based on scientific evidence. Even though multiple recent studies supported more conservative management by illustrating successful results of the digit salvage technique, especially for "in situ" SUM, this salvage approach is not well supported for the more aggressive type of the "invasive" SUM; herein, we salvaged two cases of "invasive" SUM. Case Presentation. We present two cases of invasive SUM without radiographic evidence of intraosseous involvement, where we avoided digit amputation for both invasive subungual squamous cell carcinoma of the thumb and invasive subungual melanoma of the ring finger. Both were salvaged by using a triple technique under awake local anesthesia which included (I) radical excision of the nail bed unit including both eponychium and periosteum, (II) dorsal cortical bone shaving using a high-speed burr for the distal phalanx, and (III) flap coverage. Brunelli flap was used for the thumb in the first case, and V-Y plasty combined with proximal nail fold advancement flap was used for the ring finger in the second case. There was no evidence of local or distant recurrence, with a good functional outcome after 2.5 years in the first case and 2 years in the second. CONCLUSION: Ensuring complete resection with negative margins while preserving the functionality of the affected digit is considered to be the optimal challenge in treating "invasive" subungual malignancies. These two case reports contribute by reporting a successful digit salvage. The safety of this procedure could be confirmed by larger series and longer follow-up periods.

A Predictive Model for Acute Respiratory Distress Syndrome Mortality Using Red Cell Distribution Width.

METHODS: This observational retrospective cohort study includes 318 ARDS patients extracted from an ICU database between the years of 2001 and 2008. Clinical factors including age, gender, comorbidity score, Sequential Organ Failure Assessment (SOFA) score, and PaO2/FiO2 ratio were chosen for the base model to predict ICU mortality. The RDW value at the time of ARDS diagnosis was added to the base model to determine if it improved its predictive ability. RESULTS: 318 subjects were included; 113 (36%) died in the ICU. AUC for the base model without RDW was 0.76, and 0.78 following the addition of RDW [p=0.048]. The NRI was 0.46 (p=0.001), indicating that, in 46% of patients, the predictive probability of the model was improved by the inclusion of RDW. CONCLUSIONS: Adding RDW at time of ARDS diagnosis improved discrimination in a model using 4 clinical factors to predict ICU mortality.

BMI is Associated with Coronavirus Disease 2019 Intensive Care Unit Admission in African Americans.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has disproportionately impacted the African American community. This study aims to identify the risk factors for severe COVID-19 disease in African American patients. METHODS: This was a retrospective cross-sectional analysis of African American patients with COVID-19 treated between March 12 and April 9, 2020, at a single tertiary center. The primary outcome of interest was severe disease defined as those requiring intensive care unit (ICU) admission. RESULTS: The study included 158 consecutive patients. The mean age was 57 years, and 61% were women. The mean (SD) of BMI was 33.2 (8.6) kg/m2 . Overall, patients admitted to the ICU were older (62 vs. 55 years, P = 0.003) and had higher BMI (36.5 kg/m2 vs. 31.9 kg/m2 , P = 0.002). In unadjusted and adjusted analysis, the factors most associated with ICU admission in this sample were age (adjusted odds ratio [aOR]: 1.073; 95% CI: 1.033-1.114), BMI (aOR: 1.115; 95% CI: 1.052-1.182), and lung disease (aOR: 3.097; 95% CI: 1.137-8.437). CONCLUSIONS: This study identified risk factors for severe disease in COVID-19, specifically in an African American population. Further inclusive research aimed at optimizing clinical care relevant to the African American population is critical to ensure an equitable response to COVID-19.

Using Bronchoscopic Lung Cryobiopsy and a Genomic Classifier in the Multidisciplinary Diagnosis of Diffuse Interstitial Lung Diseases.

BACKGROUND: Challenges remain for establishing a specific diagnosis in cases of interstitial lung disease (ILD). Bronchoscopic lung cryobiopsy (BLC) has impacted the diagnostic impression and confidence of multidisciplinary discussions (MDDs) in the evaluation of ILD. Reports indicate that a genomic classifier (GC) can distinguish usual interstitial pneumonia (UIP) from non-UIP. RESEARCH QUESTION: What is the impact of sequentially presented data from BLC and GC on the diagnostic confidence of MDDs in diagnosing ILD? STUDY DESIGN AND METHODS: Two MDD teams met to discuss 24 patients with ILD without a definitive UIP pattern. MDD1 sequentially reviewed clinical-radiologic findings, BLC, and GC. MDD2 sequentially reviewed GC before BLC. At each step in the process the MDD diagnosis and confidence level were recorded. RESULTS: MDD1 had a significant increase in diagnostic confidence, from 43% to 93% (P = .023), in patients with probable UIP after the addition of GC to BLC. MDD2 had an increase in diagnostic confidence, from 27% to 73% (P = .074), after the addition of BLC to GC. The concordance coefficients and percentage agreement of categorical idiopathic pulmonary fibrosis (IPF) and non-IPF diagnoses were as follows: GC vs MDD1: 0.92, 96%; GC vs MDD2: 0.83, 92%; BLC1 vs MDD1: 0.67, 83%; BLC2 vs MDD2: 0.66, 83%. INTERPRETATION: GC increased diagnostic confidence when added to BLC for patients with a probable UIP pattern, and in appropriate clinical settings can be used without BLC. In contrast, BLC had the greatest impact regarding a specific diagnosis when the likelihood of UIP was considered low following clinical-radiographic review.

Metabolic Syndrome and COVID-19 Mortality Among Adult Black Patients in New Orleans.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity, and diabetes. We examined the association between hypertension, obesity, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. RESEARCH DESIGN AND METHODS: Data were collected from 287 consecutive patients with COVID-19 hospitalized at two hospitals in New Orleans, LA from 30 March to 5 April 2020. MetS was identified per World Health Organization criteria. RESULTS: Among 287 patients (mean age 61.5 years; female, 56.8%; non-Hispanic black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR] 3.42 [95% CI 1.52-7.69]), intensive care unit (ICU) (aOR 4.59 [CI 2.53-8.32]), invasive mechanical ventilation (IMV) (aOR 4.71 [CI 2.50-8.87]), and acute respiratory distress syndrome (ARDS) (aOR 4.70 [CI 2.25-9.82]) compared with non-MetS. Multivariable analyses of hypertension, obesity, and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR 2.18 [CI, 1.25-3.81]), ARDS (aOR 2.44 [CI 1.28-4.65]), and IMV (aOR 2.36 [CI 1.33-4.21]). Diabetes was associated with ICU (aOR 2.22 [CI 1.24-3.98]) and IMV (aOR 2.12 [CI 1.16-3.89]). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, CRP, and lactate dehydrogenase (LDH) were associated with mortality (CRP [aOR 3.66] [CI 1.22-10.97] and LDH [aOR 3.49] [CI 1.78-6.83]). CONCLUSIONS: In predominantly black patients hospitalized for COVID-19, the clustering of hypertension, obesity, and diabetes as MetS increased the odds of mortality compared with these comorbidities individually.

Pharmacotherapy and adjunctive treatment for idiopathic pulmonary fibrosis (IPF).

Idiopathic pulmonary fibrosis (IPF) is an advancing and fatal lung disease with increasing incidence and prevalence. Nintedanib and pirfenidone were approved by the FDA for the treatment of IPF in 2014 based on positive phase 3 trials, and both of these antifibrotic drugs are conditionally recommended in the 2015 ATS/ERS/JRS/ALAT Clinical Practice Guideline. Although an improvement over previously suggested therapies, their capacity to reduce, but not completely arrest or improve, lung function over time presents an opportunity for novel or add-on pharmacologic agents. The purpose of this review is to deliver a brief overview of the results of phase 3/4 IPF trials with pirfenidone and nintedanib, as well as highlight encouraging results of phase 1/2 trials with novel therapies. Long-term studies indicate that pirfenidone and nintedanib are effective IPF treatments, with acceptable safety and tolerability. The combination of pirfenidone and nintedanib appear safe. Promising results have recently been made public for several phase 2 trials with novel targets, including the autotaxin-lysophosphatidic acid (ATX/LPA) pathway, connective tissue growth factor (CTGF), pentraxin-2, G protein-coupled receptor agonists/antagonists, αvß6 integrin, and galectin-3. Results of treatments directed at gastro-esophageal reflux in patients with IPF have also been published. Currently, monotherapy with pirfenidone or nintedanib is the mainstay of pharmacological treatment for IPF. Innovative therapies along with combinations of pharmacological agents hold great promise for the future.

Hematologic markers of distant metastases in gastric cancer.

BACKGROUND: High neutrophil-lymphocyte ratio (NLR) is associated with poor overall survival (OS) in gastric cancer. This study evaluates whether NLR, in addition to other parameters including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are associated with distant metastases, a common and poor prognostic feature of gastric cancer. METHODS: Clinical data from 502 gastric cancer patients treated at King Hussein Cancer Center (Amman, Jordan) have been retrospectively reviewed. We examined the association between ANC, ALC, AEC, AMC, NLR, MLR and PLR with the baseline distant metastases and OS. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal NLR cutoff value for association with distant metastases. RESULTS: Univariate and multivariate analyses showed that patients with high baseline NLR (≥3.9) had more distant metastases on presentation than patients with low NLR (<3.9), (P value: 0.0001 and 0.0005, respectively). Furthermore, patients with high baseline ANC (≥6,015/µL), AEC (≥215/µL), PLR (≥0.15) had more distant metastases in comparison to patients with low baseline ANC (<6,015/µL), AEC (<215/µL), PLR (<0.15) (P value: 0.024, 0.001, and 0.001, respectively). High ANC, NLR, MLR and PLR are associated with poor OS (P value: 0.046, 0.0003, 0.027, and <0.0001, respectively). CONCLUSIONS: High ANC, AEC, NLR, and PLR are associated with distant metastases on presentation in gastric cancer. In the era of cancer immunotherapy, whether these immune phenomena predict the response of gastric cancer to immunotherapy is unknown.

Reduction of inhibition in the inferior colliculus after inner hair cell loss.

Effects of carboplatin-induced partial loss of inner hair cells on rate-level functions of neurons in the central nucleus of the inferior colliculus of the same chinchillas before and 1-3 months after carboplatin treatment were examined. Partial inner hair cell loss caused only a small elevation of response thresholds but induced a significant increase in the proportion of monotonic and a significant decrease in the proportion of non-monotonic rate-level functions at the characteristic frequency of 210 multiunits. This indicates that inhibition in the inferior colliculus is reduced after sensory deafferentation. We conclude that some of the functional changes reported in the auditory cortex after peripheral deafferentation are already realized at the level of the inferior colliculus.

Inhibitory and excitatory response areas of neurons in the central nucleus of the inferior colliculus in unanesthetized chinchillas.

In unanesthetized chinchillas, we determined excitatory and inhibitory response regions of neurons in the central nucleus of the inferior colliculus (ICc). The responses of 250 multiunits and 47 single units in the ICc to one- and two-tone stimuli were measured by extracellular recordings. The one-tone excitatory response area of ICc neurons from awake chinchillas was classified as either narrow with a steep high-frequency slope >140 dB/oct (type 1), broad with a high-frequency slope <140 dB/oct (type 2), or complex with a negative high-frequency slope (type 3). One-tone inhibition was prominent only in units with a high spontaneous firing rate. As revealed with two-tone stimuli, inhibition in the ICc of awake chinchillas and its relation to excitatory response regions was different from what is reported in anesthetized animals. The two-tone inhibitory responses were classified as follows: (1) inhibitory regions of equal strength on both sides of the characteristic frequency; (2) asymmetrical inhibitory regions, more prominent at the high-frequency side of the characteristic frequency; (3) strong inhibitory regions overlying most of the one-tone excitatory response region; (4) inhibitory response regions lying only within the one-tone excitatory response region; and (5) neurons without clear two-tone inhibition. One-tone and two-tone inhibitory regions of the same unit were markedly different in 66% of the units with a high spontaneous rate. The neural response to frequencies within the inhibitory regions often was an onset response followed by inhibition. Excitatory and inhibitory response properties were similar over considerable penetration distances (600-1,000 microm) in a particular dorso-ventral recording track.