Toward optical spectroscopy-guided lung biopsy: Demonstration of tissue-type classification.

The diagnostic yield of standard tissue-sampling modalities of suspected lung cancers, whether by bronchoscopy or interventional radiology, can be nonoptimal, varying with the size and location of lesions. What is needed is an insitu sensor, integrated in the biopsy tool, to objectively distinguish among tissue types in real time, not to replace biopsy with an optical diagnostic, but to verify that the sampling tool is properly located within the target lesion. We investigated the feasibility of elastic scattering spectroscopy (ESS), coupled with machine learning, to distinguish lung lesions from the various nearby tissue types, in a study with freshly-excised lung tissues from surgical resections. Optical spectra were recorded with an ESS fiberoptic probe in different areas of the resected pulmonary tissues, including benign-margin tissue sites as well as the periphery and core of the lesion. An artificial-intelligence model was used to analyze, retrospectively, 2032 measurements from excised tissues of 35 patients. With high accuracy, ESS was able to distinguish alveolar tissue from bronchi, alveolar tissue from lesions, and bronchi from lesions. This ex vivo study indicates promise for ESS fiberoptic probes to be integrated with surgical intervention tools, to improve reliability of pulmonary lesion targeting.

An unusual case of postpartum dyspnea.

A 40-year-old South Asian woman was admitted in active labor at 38 weeks' gestation. She had an unremarkable medical history with routine prenatal care, negative HIV testing results, and an uneventful pregnancy. She received a Bacillus Calmette-Guérin vaccine during childhood and reportedly had a subsequent positive purified protein-derivative test result 1 year prior to conception. She never smoked and had seven normal term pregnancies.

Predicting the Need for Upfront Combination Therapy in Pulmonary Arterial Hypertension.

BACKGROUND: Combination therapy is commonly used for pulmonary arterial hypertension (PAH) treatment. We aimed to identify factors that may predict the need for future combination therapy. METHODS: We conducted a retrospective chart review of consecutive patients with PAH in an aim to describe baseline clinical, echocardiogram, and hemodynamic characteristics of patients who eventually required combination therapy during the course of their disease and compared them to the ones who were maintained on monotherapy. RESULTS: The monotherapy group was followed for an average of 31.8 ± 18.8 months and the combination therapy group was followed for an average of 28.7 ± 13.6 months. Among the 71 patients analyzed, a significantly higher number of patients who eventually required combination therapy belonged to World Health Organization functional class 3 (45% vs 37%) and 4 (23% vs 0) at baseline, compared with those on monotherapy (P < .05). Combination group also had a higher Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL) PAH risk score at presentation. End of 6-minute walk test (6MWT), oxygen saturation (Spo 2) was also lower in the combination therapy group, 86% ± 8% versus 91% ± 7% (P < .05). Patients who eventually required combination therapy were more frequently noticed to have right ventricular enlargement, right atrial enlargement, and had a higher resting estimated right ventricular systolic pressure (RVSP). Right heart catheterization-derived hemodynamics data at baseline showed that the combination therapy group had a higher mean pulmonary artery (PA) pressure, lower pulmonary capillary wedge pressure, lower cardiac output, and higher pulmonary vascular resistance (PVR). On univariate analysis, only PVR ≥300 dyne·s/cm(5), mean PA pressure of ≥40 mm Hg, estimated RVSP ≥ 60 mm Hg, PAH risk score ≥ 10, and end of 6MWT saturation of ≤ 90% were of significance. CONCLUSION: Patients with PAH who require combination therapy in the course of their disease have worse hemodynamics, PAH risk score, functional class, and end of 6MWT oxygen saturation at the time of presentation compared to patients maintained on monotherapy.

Differential effects of alcohol upon gluconeogenesis from lactate in young and old hepatocytes.

The purpose of this study was to determine the effect of age upon hepatic gluconeogenesis (HGN) from lactate in the presence of various concentrations of alcohol from young (3 months) and old (24 months) male rats. After a 24-hour fast, livers were perfused with collagenase and the hepatocytes were isolated. Aliquots of the cell suspension were placed in Krebs-Henseleit buffer and incubated with lactate, [U-(14)C]lactate, and nine different concentrations of ethanol (EtOH) for 30 min. Dose-effect curves were generated for the determination of maximal and half-maximal alcohol-induced inhibition on gluconeogenesis. There were no significant differences in basal HGN (lactate only and no EtOH) between young and old hepatocytes, 86.9+/-6.3 nmol/mg protein/30 min. The addition of ethanol significantly reduced HGN from lactate in both groups. At the highest ethanol concentration (15 mM), the glucose production was inhibited more from old, 46.1+/-1.2 nmol/mg protein/30 min, compared to young hepatocytes, 56.0+/-1.6 nmol/mg protein/30 min. The greater age-related reduction in HGN was confirmed by the minimal glycogenolysis, and the concomitant decline in [U-(14)C]glucose production, lactate uptake, and [U-(14)C]lactate uptake. The results suggest that alcohol elicits a greater inhibition upon HGN from lactate in old compared to young liver cells.

Chronic alcohol consumption yields sex differences in whole-body glucose production in rats.

AIMS: The effects of chronic alcohol consumption (8 weeks) on glucose kinetics, in the absence (water, 4 g/kg) and presence of an acute ethanol dose (4 g/kg), were examined in 48 h fasted male and female Wistar rats. METHODS: Primed continuous infusions of [6-3H]- and [U-14C]glucose were employed to assess rates of glucose appearance (Ra), glucose disappearance (Rd), and apparent glucose carbon recycling. RESULTS: After injecting the male and female controls with water, there were no significant alterations in glucose kinetics. Compared to controls, chronic alcohol-fed female animals (injected with water) demonstrated significantly lower: glucose Ra, blood glucose concentration, and apparent glucose carbon recycling for a majority of the experimental period. In separate groups injected with ethanol, the glucose Ra fell by 31% for male rats fed the control diet (MC), 43% for male rats fed the ethanol diet (ME), 29% for female rats fed the control diet (FC), and 42% for female rats fed the ethanol diet (FE). Further, compared to controls (MC and FC), the blood glucose concentration was significantly lower prior to and following the ethanol injection for FE. In addition, FE animals had significantly lower rates of glucose Ra and glucose carbon recycling compared to controls prior to and after the ethanol injection. ME animals demonstrated similar declines in glucose Ra (compared to FE), but only after the ethanol injection. Conversely, ME were able to match the decrease in glucose Ra with comparable declines in glucose Rd resulting in blood glucose concentrations that did not differ from controls. CONCLUSIONS: Chronic alcohol consumption results in sex differences in whole-body glucose production and glucose regulation.

Hepatic gluconeogenic capacity from various precursors in young versus old rats.

Hepatic gluconeogenic capacity was studied in young (4 months of age) and old (24 months of age) male Fischer 344 rats fasted for 24 hours using the isolated hepatocyte technique. Following the isolation of liver cells, the following precursors were added to the cell suspensions and incubated for 30 minutes: lactate (5 mmol/L), pyruvate (5 mmol/L), alanine (5 mmol/L), glutamine (5 mmol/L), oxaloacetate (5 mmol/L), glycerol (5 mmol/L), dihydroxyacetone (10 mmol/L), fructose (10 mmol/L), or saline (no precursor addition). To confirm that glucose production reflects gluconeogenic capacity, there was significant depletion of hepatic glycogen after the 24-hour fast and minimal alterations in glycogen content once substrates were added. Adjusting the gluconeogenic rates to reflect 100% cell viability resulted in no difference between young and old animals for any substrate used with the sole exception of fructose. The hepatic glucose production from fructose was 34% greater for young versus old animals. The results suggest that following a period of starvation the basal glucose production rates from hepatocytes, incubated with precursors entering the gluconeogenic pathway prior to fructose-6-phosphate, are equivalent in young and old rats.