Cross-linked, biodegradable, cytocompatible salicylic acid based polyesters for localized, sustained delivery of salicylic acid: an in vitro study.

In order to suppress chronic inflammation while supporting cell proliferation, there has been a continuous surge toward development of polymers with the intention of delivering anti-inflammatory molecules in a sustained manner. In the above backdrop, we report the synthesis of a novel, stable, cross-linked polyester with salicylic acid (SA) incorporated in the polymeric backbone and propose a simple synthesis route by melt condensation. The as-synthesized polymer was hydrophobic with a glass transition temperature of 1 °C, which increases to 17 °C upon curing. The combination of NMR and FT-IR spectral techniques established the ester linkages in the as-synthesized SA-based polyester. The pH-dependent degradation rate and the rate of release of salicylic acid from the as-synthesized SA-based polymer were studied at physiological conditions in vitro. The polyester underwent surface erosion and exhibited linear degradation kinetics in which a change in degradation rate is observed after 4-10 days and 24% mass loss was recorded after 4 months at 37 °C and pH 7.4. The delivery of salicylic acid also showed a similar change in slopes, with a sustained release rate of 3.5% in 4 months. The cytocompatibility studies of these polyesters were carried out with C2C12 murine myoblast cells using techniques like MTT assay and flow cytometry. Our results strongly suggest that SA-based polyester supports cell proliferation for 3 days in culture and do not cause cell death (<7%), as quantified by propidium iodide (PI) stained cells. Hence, these polyesters can be used as implant materials for localized, sustained delivery of salicylic acid and have applications in adjuvant cancer therapy, chronic wound healing, and as an alternative to commercially available polymers like poly(lactic acid) and poly(glycolic acid) or their copolymers.

Single glucose challenge test procedure for diagnosis of gestational diabetes mellitus: a Jammu cohort study.

AIM: To elucidate an evidence based Single Glucose Challenge test to diagnose Gestational Diabetes Mellitus (GDM). METHOD: This study included 500 pregnant women in 16-32 weeks of gestation. They underwent 75g Oral Glucose Challenge test irrespective of the last meal timing and 2 hr venous blood was drawn. After 3 days they underwent 75g OGTT in the fasting state and their 2 hr blood was drawn. Plasma glucose was estimated in both samples by GOD-POD method. GDM was diagnosed with 2hr Plasma glucose (PG) > or = 7.8 mmol/l (> or = 140 mg/dl) based on WHO criteria. The data was analysed by computer software Microsoft excel for windows and epi-info version 6.0, CDC, Atlanta, GA. RESULTS: Among 500 women, 55(11%) were diagnosed as GDM by WHO criteria. It was observed that there was no statistical difference (p > 0.05) between 2 hr PG of GCT and 2 hr PG of WHO recommended method. CONCLUSION: This Single Glucose Challenge test procedure is cost-effective, evidence based and patient friendly approach to diagnosis Gestational Diabetes Mellitus.

High nocturnal periodic breathing reported by PAP adherence data predicts decompensation of heart failure.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) often coexists with heart failure (HF) and is commonly treated with positive airway pressure (PAP) therapy. Periodic breathing (PB) may be present in HF and is an indicator of poor prognosis, but there is no easy way to detect PB in an outpatient setting. However, it can be detected by analyzing PAP usage data. The study aimed to assess if high PB% detected by PAP machine could predict impending HF exacerbation and if better PAP adherence is associated with reduced hospitalization and mortality. METHODS: We retrospectively reviewed medical records of 115 patients with OSA from the sleep clinic of our VA Medical Center. The cross-sectional data on demographics, labs, PAP adherence, PB% in the previous 30 days, echocardiogram in the previous 6 months, and hospitalizations and mortality in the subsequent 180 days were extracted. Based on left ventricular ejection fraction (LVEF), patients were classified into (1) HF with normal-midrange LVEF (LVEF ≥40%, n = 74) and (2) HF with reduced LVEF (LVEF < 40%, n = 41). Pairwise correlation and linear regressions were done to assess predictors of PB%. Binomial and logistic regressions assessed the relationship of PB% and PAP adherence with hospitalization from HF and all-cause mortality. RESULTS: In the HF with reduced LVEF group, the mean PB% was 2.6 times higher (P < .001) and PAP adherence was 29% lower (P < .001). PB% positively correlated with brain natriuretic peptide level (r = .447, P < .01) and number of hospitalizations (r = .331, P < .01). Higher PB% negatively correlated with LVEF (r = -.423, P < .01) and estimated glomerular filtration rate (r = -.246, P < .01). Every 10% increase in PAP adherence decreased odds of hospitalization by 0.78 times (P < .001) and odds of death by 0.86 (P = .043). CONCLUSIONS: High PB% detected by PAP machine data is a predictor of impending HF exacerbation and hospitalization. Improved PAP adherence and optimization of medical therapy may reduce hospitalization and all-cause mortality. CITATION: Ullah MI, Tamanna S, Bhagat R. High nocturnal periodic breathing reported by PAP adherence data predicts decompensation of heart failure. J Clin Sleep Med. 2023;19(3):431-441.

Pulmonary emboli from therapeutic sodium hyaluronate.

A patient presented with shortness of breath and pleuritic pain shortly after bilateral knee synovial injections with sodium hyaluronate (HA). He was discharged after a brief hospitalization without a diagnosis when no Doppler or radiologic evidence of deep vein thrombosis or pulmonary emboli was found. Radiologic studies found patchy ground glass opacities that were predominantly peripheral in disposition, with prominent septal lines in the lungs; a subsequent pulmonary function test showed a reduced diffusing capacity of the lung for carbon monoxide (D(LCO)). These results prompted a lung biopsy that revealed multiple emboli composed of HA and fibrin in medium size pulmonary arteries, enlarged lymphatic vessels, and a bone marrow embolus. This is the first report of HA emboli following therapeutic HA injections and demonstrates that pulmonary function tests can be used to infer the reduction in pulmonary vascular area consequent to pulmonary emboli, and so can contribute to the detection of pulmonary emboli in unusual presentations.

Prevalence of gestational diabetes mellitus (GDM) and its outcomes in Jammu region.

INTRODUCTION: The present study seeks to evaluate the prevalence and outcomes of gestational diabetes mellitus (GDM) from Jammu region. METHODS: During the period of study, women at 24th to 28th week of gestation were investigated for the presence of GDM according to Diabetes In Pregnancy Study Group India (DIPSI) guidelines. The maternal and fetal outcomes were recorded and compared with (a) non-diabetic control group and (b) non-interventional untreated GDM group. RESULTS: The overall prevalence of GDM was found to be 6.94%. In the untreated group, family history of diabetes was 24.19%, caesarean section 22.58% and preterm delivery 16.13%, whereas the prevalence of macrosomia was 16.2% and shoulder dystocia 6.45%. These figures were found to be significantly higher when compared to the data obtained from the treated GDM group which was as follows: caesarean section 8.5%, preterm delivery 4.2%, macrosomia 10% and shoulder dystocia 1.2%. CONCLUSION: The study emphasizes the importance of screening for GDM and timely optimum intervention for a significant positive effect on both maternal as well as foetal outcomes in pregnancy. This also builds a strong case for adherence to DIPSI guidelines in diagnosis and management of GDM.

The ventilation of buildings and other mitigating measures for COVID-19: a focus on wintertime.

The year 2020 has seen the emergence of a global pandemic as a result of the disease COVID-19. This report reviews knowledge of the transmission of COVID-19 indoors, examines the evidence for mitigating measures, and considers the implications for wintertime with a focus on ventilation.

Displacement ventilation: a viable ventilation strategy for makeshift hospitals and public buildings to contain COVID-19 and other airborne diseases.

The SARS-CoV-2 virus has so far infected more than 31 million people around the world, and its impact is being felt by all. Patients with diseases such as COVID-19 should ideally be treated in negative pressure isolation rooms. However, due to the overwhelming demand for hospital beds, patients have been treated in general wards, hospital corridors and makeshift hospitals. Adequate building ventilation in hospitals and public spaces is a crucial factor to contain the disease (Escombe et al. 2007 PLoS Med. 4; Escombe et al. 2019 BMC Infect. Dis. 19, 88 (doi:10.1186/s12879-019-3717-9); Morawska & Milton 2020 Clin. Infect. Dis. ciaa939. (doi:10.1093/cid/ciaa939)), to exit lockdown safely, and reduce the chance of subsequent waves of outbreaks. A recently reported air-conditioner-induced COVID-19 outbreak caused by an asymptomatic patient, in a restaurant in Guangzhou, China (Lu et al. 2020 Emerg. Infect. Dis. 26) exposes our vulnerability to future outbreaks linked to ventilation in public spaces. We argue that displacement ventilation (either mechanical or natural ventilation), where air intakes are at low level and extracts are at high level, is a viable alternative to negative pressure isolation rooms, which are often not available on site in hospital wards and makeshift hospitals. Displacement ventilation produces negative pressure at the occupant level, which draws fresh air from outdoors, and positive pressure near the ceiling, which expels the hot and contaminated air out. We acknowledge that, in both developed and developing countries, many modern large structures lack the openings required for natural ventilation. This lack of openings can be supplemented by installing extract fans. We have also discussed and addressed the issue of the 'lock-up effect'. We provide guidelines for such mechanically assisted, naturally ventilated makeshift hospitals.

Improving PTSD Symptoms and Preventing Progression of Subclinical PTSD to an Overt Disorder by Treating Comorbid OSA With CPAP.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and posttraumatic stress disorder (PTSD) are common in United States veterans. These conditions often coexist and symptoms overlap. Previous studies reported improvement in PTSD symptoms with continuous positive airway pressure (CPAP) therapy for comorbid OSA but its effect has not been assessed in a non-PTSD cohort. We have prospectively assessed the effect of CPAP therapy on clinical symptom improvement as a function of CPAP compliance levels among PTSD and non-PTSD veterans. METHODS: Veterans in whom OSA was newly diagnosed were enrolled in our study (n = 192). Assignment to PTSD and non-PTSD cohorts was determined by chart review. Each patient completed the military version of the PTSD Checklist (PCL), Epworth Sleepiness Scale (ESS), and reported nightmare frequency (NMF) at baseline and 6 months after CPAP therapy. CPAP adherence was objectively documented from machine compliance data. RESULTS: We had complete data for 177 veterans (PTSD n = 59, non-PTSD n = 118) for analysis. The mean ages were 51.24 years in the PTSD cohort and 52.36 years in the non-PTSD cohort (P = .30). In the PTSD cohort, the mean total PCL score (baseline = 66.06, post-CPAP = 61.27, P = .004, d = -0.34) and NMF (baseline = 4.61, post-CPAP = 1.49, P = .0001, d = -0.51) decreased after 6 months of CPAP treatment. Linear regression analysis showed that the CPAP compliance was the only significant predictor for these changes among veterans with PTSD (PCL score: P = .033, R2 = .65; NMF; P = .03, R2 = .61). Further analysis by CPAP compliance quartiles in this cohort (Q1 = 0% to 25%, Q2 = 26% to 50%, Q3 = 51% to 75%, Q4 > 75%) revealed that mean total PCL score declined in Q2 (change = -3.91, P = .045, d = 0.43), Q3 (change = -6.6, P = .002, d = 0.59), and Q4 (change = -7.94, P = .037, d = 0.49). In the non-PTSD cohort, the PCL score increased despite CPAP therapy in lower CPAP compliance quartiles Q1 (change = 8.71, P = .0001, d = 0.46) and Q2 (change = 4.51, P = .046, d = 0.27). With higher CPAP compliance (in Q3 and Q4) in this cohort, the mean total PCL scores slightly improved with CPAP but they were not statistically significant (P > .05). CONCLUSIONS: CPAP treatment reduces total PCL score and NMF in veterans with PTSD and OSA. Those with overt PTSD respond to even lower CPAP compliance, whereas non-PTSD patients require higher compliance to achieve any symptom improvement. Poor CPAP compliance results in increased PCL score in non-PTSD veterans and may lead to overt PTSD if the OSA remains undertreated. COMMENTARY: A commentary on this article appears in this issue on page 1121.

Preventing Ventilator-Associated Infections.

Mechanical ventilator use is fraught with risk of complications. Ventilator-associated pneumonia (VAP) is a common complication that prolongs stays on the ventilator and increases mortality and costs. The Centers for Disease Control and Prevention recommend the use of the term, ventilator-associated event. Prevention and/or interruption of cycle of inflammation, colonization of respiratory tract, and ventilator-associated tracheobronchitis are key to managing VAP. Modifying risk factors using a ventilator bundle is considered standard of care. The contentious factors and the lack of support for early tracheotomy, parenteral nutrition, and monitoring of gastric residuals are also addressed. Finally, the role of ventilator-associated tracheobronchitis in VAP is discussed.

Safety and efficacy of weekly oral oltipraz in chronic smokers.

Cigarette smoking is thought to contribute to carcinogenesis by formation of DNA adducts of tobacco smoke constituents leading to genotoxic damage. The dithiolethione, oltipraz, is a putative cancer chemopreventive agent that induces phase II detoxifying enzymes in preclinical models and reduces aflatoxin adducts in humans living in areas with high dietary levels. To determine if oltipraz could reduce adduct levels of tobacco smoke constituents in the lungs and other target organs, chronic smokers were enrolled to one of three arms: 400 or 200 mg/wk oral oltipraz or placebo. Endobronchial tissue and bronchoalveolar lavage were done before and after 12 weeks of drug treatment; peripheral blood, urine, and oral saline rinse were also collected. Toxicity was assessed every 4 weeks. Fifty-nine of the 77 enrolled subjects completed the study. Of those receiving oltipraz, 15% experienced grade 2/3 toxicity, which was predominantly gastrointestinal. All subject withdrawals occurred in the oltipraz groups. There was no significant difference between pre- and post-polycyclic aromatic hydrocarbon-DNA adduct levels in lung epithelial cells measured by immunoperoxidase staining between treatment and placebo groups. Likewise, no significant differences were found in polycyclic aromatic hydrocarbon or benzo(a)pyrene-7,8-diol-9,10-epoxide adducts measured in blood, oral lining cells, or bladder lining cells. There was also no increase in mRNA or enzymatic activity of phase II enzymes and no change in glutathione levels. Thus, despite moderate drug-related toxicity, there was no significant effect on pharmacodynamic or surrogate risk biomarkers. Other agents with lower toxicity and greater activity to induce phase II enzymes are needed to definitively test the detoxification-induction paradigm in smokers.

Pulmonary sarcoidosis following stem cell transplantation: is it more than a chance occurrence?

Noninfectious pulmonary complications are one of the major side effects of hematopoetic stem cell transplant (HSCT); however, the development of pulmonary sarcoidosis post-HSCT is uncommon, with only three cases previously reported. In each of those cases, sarcoidosis was also diagnosed in the stem cell donor. We now report four cases of de novo pulmonary sarcoidosis occurring post-HSCT (3 autologous HSCT and 1 allogeneic HSCT). We suggest that pulmonary sarcoidosis may develop following either autologous or allogeneic HSCT, and the prevalence may be 10-fold higher than that of the normal population.

Sleep-disordered breathing symptoms among African-Americans in the Jackson Heart Study.

BACKGROUND: Sleep-disordered breathing (SDB) is an increasingly recognized risk factor for cardiovascular disease (CVD). Limited data are available from large African American cohorts. METHODS: We examined the prevalence, burden, and correlates of sleep symptoms suggestive of SDB and risk for obstructive sleep apnea (OSA) in the Jackson Heart Study (JHS), an all-African-American cohort of 5301 adults. Data on selected daytime and nighttime sleep symptoms were collected using a modified Berlin questionnaire during the baseline examination. Risk of OSA was calculated according to published prediction model. Age and multivariable-adjusted logistic regression models were used to examine the associations between potential risk factors and measures of sleep. RESULTS: Sleep symptoms, burden, and risk of OSA were high among men and women in the JHS and increased with age and obesity. Being married was positively associated with sleep symptoms among women. In men, poor to fair perceived health and increased levels of stress were associated with higher odds of sleep burden, whereas prevalent hypertension and CVD were associated with higher odds of OSA risk. Similar associations were observed among women with slight variations. Sleep duration <7h was associated with increased odds of sleep symptoms among women and increased sleep burden among men. Moderate to severe restless sleep was consistently and positively associated with odds of adverse sleep symptoms, sleep burden, and high risk OSA. CONCLUSIONS: Sleep symptoms in JHS had a strong positive association with features of visceral obesity, stress, and poor perceived health. With increasing obesity among younger African Americans, these findings are likely to have broad public health implications.

Endobronchial recurrence of gastric mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a diagnostic challenge when arising from bronchiolar submucosal tissue. The case herein describes a man with a lung mass and a remote history of gastric MALT lymphoma. After undergoing a bronchoscopic examination and tissue sampling, he was diagnosed with pulmonary recurrence of gastric MALT lymphoma. The diagnosis of MALT lymphoma in the lung can be challenging. Radiographic findings are typically nonspecific, and tissue biopsy by surgical means is often required. The diagnosis of bronchus-associated lymphoid tissue lymphoma has been previously demonstrated bronchoscopically when a needle aspiration is performed. This case supports the position that bronchoscopy with needle aspiration, and flow cytometry should be performed in all patients in whom pulmonary MALT lymphoma is suspected.

Leptin is inversely associated with lung function in African Americans, independent of adiposity: the Jackson Heart Study.

Leptin, a 16-kDa protein, has proinflammatory properties and has been linked to respiratory physiological responses in majority white populations. Little is known, however, about the relationship of leptin with lung function in nonwhites. Cross-sectional associations of circulating serum leptin concentrations with forced expiratory volume in 1 s (FEV(1)), FEV in 6 s (FEV(6)), and vital capacity (FVC), assessed by spirometry, were examined in 4,679 African-American men and women participants (54.3 ± 12.4 years; 62.7% women) in the Jackson Heart Study (JHS). The independent association of leptin was examined in relation to FEV(1), FEV(6), and FVC% predicted after adjustment for age, education, smoking status, pack-years of cigarette smoking, respiratory medication use, and menopausal status in women; additional adjustment included total body weight, waist circumference, and BMI. Serum leptin was inversely related to FEV(1), FEV(6), and FVC% predicted values in men. A dose-response relationship was observed with men in the highest leptin quartile having a significantly lower lung function compared to men in the lower leptin quartile. BMI significantly modified this relationship in women: leptin was most consistently associated with lung function in obese women, less consistent in overweight women, and absent in normal-weight women. Serum leptin concentration was strongly, inversely, and independently associated with lung function in African Americans, especially African-American men and obese women.

Determination of derivatized urea in exhaled breath condensate by LC-MS.

Elevation in one or more compounds in exhaled breath condensate (EBC) has been reported to be related to one or another lung disease. The increased concentration might be caused by increased chemicals in the airway surface liquid. However, it might also be due to an increased delivery of liquid samples into the airstream. Being evenly distributed throughout the body, urea is a likely candidate for a marker of such dilution. A liquid chromatography-tandem mass spectrometry method was developed for determination of EBC urea. Urea in EBC samples was converted to 2-hydroxypyrimidine (2-HPM) through a one step reaction, along with (15)N(2)-urea added as an internal standard. The product ion m/z 97/42 was selected for quantification with m/z 99/43 from (15)N(2)-2-HPM as a standard. Concentrations of urea in EBC from five lung cancer patients were found to be 35.1, 2.2, 103.5, 19.3, and 3.6 microM, respectively. The highest values were in patients dying of respiratory distress, whose lungs were filled with fluid. Lower values were seen in patients whose conditions were improving. Lately, one of the low EBC urea values was observed in a patient whose airway status did not contribute to his poor clinical condition.

Effect of smoking on spirometry of African American and White subjects.

BACKGROUND: Smoking is the single most important risk factor for COPD, yet there is still disagreement about the differences in the effect of smoking between white and African-American people. We hypothesized that the results of spirometry between smokers of the two races are equivalent if reference equations and lower limits of normal appropriate for each race are used. METHODS: We retrospectively analyzed all spirometry results in smokers over a 1-year period from the G.V. (Sonny) Montgomery VA Medical Center and excluded those that did not meet American Thoracic Society standards, or those from patients with additional medical problems. The remaining patients were classified by race and then matched for age and smoking history; 108 patients in each group were included, which met the power analysis goal of 98. The two groups were similar in age (57.5 years vs 57.0 years), smoking history (46.1 pack-years vs 46.0 pack-years), and body mass index (27.0 kg/m(2) vs 28.3 kg/m(2)) for African Americans and whites, respectively. Data were analyzed using the unpaired t test, and p values were adjusted for multiple comparisons using the Bonferroni factor. RESULTS: There were statistically significant differences between African American and white smokers in FVC (3.67 +/- 0.07 L vs 4.26 +/- 0.08 L, p = 0.001) and FEV(1) (2.33 +/- 0.07 L vs 2.72 +/- 0.08 L, p = 0.002), as expected from the normal populations; however, there were no differences in FVC as percentage of predicted (89.1 +/- 1.3% vs 86.7 +/- 1.5%, p = 0.71) and FEV(1) as percentage of predicted (71.9 +/- 2.1% vs 72.2 +/- 1.8%, p = 1.00) when the reference equations appropriate for race were used (third National Health and Nutrition Examination Survey). There were also no differences between the number of subject with abnormal FEV(1)/FVC results (56 African Americans vs 58 whites, p = 1.00) when the appropriate lower limits of normal were used. CONCLUSIONS: There are no differences in spirometry findings between African Americans and whites when abnormality is defined appropriately using reference equations and lower limits of normal for each race. By using either percentage cutoffs for abnormality, or by adjusting for African-American equations only appropriate for whites, we were able to mimic with our data conflicting results in the literature.