Citations

The volume displacements of the rib cage and abdomen of relaxed seated subjects were measured as functions of pleural pressure with the chest wall expanded by airway pressure and with the chest wall distorted by an external force applied to the rib cage. From the measured displacements for the two independent loads, the three compliances that describe the mechanical properties of the relaxed chest wall modeled as a linear elastic system with two degrees of freedom were obtained. The cross compliance that describes the coupling between the rib cage and abdomen was found to be small and positive, 0.01-0.02 1/cmH2O. The displacement of the rib cage by the external force was consistent with the displacement predicted by use of standard methods for calculating the mechanical advantage of the force.

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.

Computed tomography scans of isolated dog lung lobes at different lobe volumes were used to determine the variability of parenchymal tissue density and the variability of parenchymal volume changes on the scale of a voxel, a cube 1.5 mm on a side. The variability of tissue density increased with decreasing lobe volume. The variability of tissue density of neighboring voxels was positively correlated; the spatial correlation decreased exponentially with distance with an exponential scale of 0.3 cm. The ratio of the volume of the parenchyma within a voxel to its volume at total lobe capacity was calculated from the tissue density data at two lobe volumes. At a lobe volume of 40% total lobe capacity, the local fractional volumes were 0.42 +/- 0.12. The variability of ventilation that corresponds to this variability of fractional volume is large enough to explain the inefficiency of mixing in the isolated lobe and the slope of the alveolar plateau of nitrogen concentration in the expirate after a breath of oxygen. These results are consistent with data reported earlier on the variability of parenchymal volumes at a scale of 1–10 cm3.

Objective: Predictors of long-term functional impairment in acute respiratory failure of all causes are poorly understood. Our objective was to assess the frequency and predictors of long-term functional impairment or death after invasive mechanical ventilation for acute respiratory failure of all causes. Design: Population-based, observational cohort study. Setting: Eight adult ICUs of a single center. Patients: All adult patients from Olmsted County, Minnesota, without baseline functional impairment who received mechanical ventilation in ICUs for acute respiratory failure of all causes from 2005 through 2009. Interventions: None. Measurements and Main Results: In total, 743 patients without baseline functional impairment received mechanical ventilation in the ICU. At 1- and 5-year follow-up, the rates of survival with return to baseline functional ability were 61% (366/597) and 53% (356/669). Among 71 patients with new functional impairment at 1 year, 55% (39/71) had recovered and were alive without functional impairment at 5 years. Factors predictive of new functional impairment or death at 1 year were age, comorbidities, discharge to other than home, mechanical ventilation of 7 days or longer, and stroke. Of factors known at the time of intubation, the following are predictive of new functional impairment or death: age, comorbidities, nonsurgical condition, Acute Physiology and Chronic Health Evaluation III score, stroke, and sepsis. Post hoc sensitivity analyses revealed no significant change in predictor variables in patient populations when stroke was excluded or who received more than 48 hours of mechanical ventilation. Conclusions: At 1- and 5-year follow-up, many patients who received mechanical ventilation for acute respiratory failure from all causes are no longer alive or have new moderate-to-severe functional impairment. Functional recovery between year 1 and year 5 is possible and common. Sepsis, stroke, illness severity, age, and comorbidities predict long-term functional outcome at intubation.

OBJECTIVEThe use of nerve transfers versus nerve grafting for neonatal brachial plexus palsy (NBPP) remains controversial. In adult brachial plexus injury, transfer of an ulnar fascicle to the biceps branch of the musculocutaneous nerve (Oberlin transfer) is reportedly superior to nerve grafting for restoration of elbow flexion. In pediatric patients with NBPP, recovery of elbow flexion and forearm supination is an indicator of resolved NBPP. Currently, limited evidence exists of outcomes for flexion and supination when comparing nerve transfer and nerve grafting for NBPP. Therefore, the authors compared 1-year postoperative outcomes for infants with NBPP who underwent Oberlin transfer versus nerve grafting.METHODSThis retrospective cohort study reviewed patients with NBPP who underwent Oberlin transfer (n = 19) and nerve grafting (n = 31) at a single institution between 2005 and 2015. A single surgeon conducted intraoperative exploration of the brachial plexus and determined the surgical nerve reconstruction strategy undertaken. Active range of motion was evaluated preoperatively and postoperatively at 1 year.RESULTSNo significant difference between treatment groups was observed with respect to the mean change (pre- to postoperatively) in elbow flexion in adduction and abduction and biceps strength. The Oberlin transfer group gained significantly more supination (100° vs 19°; p < 0.0001). Forearm pronation was maintained at 90° in the Oberlin transfer group whereas it was slightly improved in the grafting group (0° vs 32°; p = 0.02). Shoulder, wrist, and hand functions were comparable between treatment groups.CONCLUSIONSThe preliminary data from this study demonstrate that the Oberlin transfer confers an advantageous early recovery of forearm supination over grafting, with equivalent elbow flexion recovery. Further studies that monitor real-world arm usage will provide more insight into the most appropriate surgical strategy for NBPP.

OBJECTIVEThis study aimed to define a set of clinicoradiological parameters with a high specificity for the diagnosis of intraneural perineurioma, obviating the need for operative tissue diagnosis.METHODSThe authors retrospectively reviewed MR images obtained in a large cohort of patients who underwent targeted fascicular biopsy and included only those patients for whom the biopsy yielded a diagnosis. Clinical and radiological findings were then tested for their ability to predict a tissue diagnosis of intraneural perineurioma. The authors propose a new set of diagnostic criteria, referred to as the Perineurioma Diagnostic Criteria. The sensitivity, specificity, positive predictive value, and negative predictive value of several clinicoradiological methods of diagnosis were compared.RESULTSA total of 195 patients who underwent targeted fascicular biopsy were included in the cohort, of whom 51 had a tissue diagnosis of intraneural perineurioma. When the clinicoradiological methods used in this study were compared, the highest sensitivity (0.86), negative predictive value (0.95), and F1 score (0.88) were observed for the decision trees generated in C5.0 and rPart, whereas the highest specificity (1.0) and positive predictive value (1.0) were observed for the Perineurioma Diagnostic Criteria.CONCLUSIONSThis study identified clinical and radiological features that are associated with a diagnosis of perineurioma. The Perineurioma Diagnostic Criteria were determined to be the following: 1) no cancer history, 2) unifocal disease, 3) moderate to severe hyperintensity on T2-weighted MR images, 4) moderate to severe contrast enhancement, 5) homogeneous contrast enhancement, 6) fusiform shape, 7) enlargement of the involved nerves, and 8) age ≤ 40 years. Use of the Perineurioma Diagnostic Criteria obviates the need for tissue diagnosis when all of the criteria are satisfied.

Objective Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions These data suggest several plausible genetic links between DLBCL and SLE.

AbstractWaldenström macroglobulinemia (WM) is an immunoglobulin M‐associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild‐type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10‐fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele‐specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype, 44 had active disease. The estimated median follow‐up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4‐16.5) for MYD88L265P versus 13.9 years (95% CI: 6.4‐29.3) for the MYD88WT (P = 0.86). The time‐to‐next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time‐to‐progression to active disease was 2.8 years (95% CI: 2.2‐3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7‐3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high‐grade lymphoma, or the development of therapy‐elated myelodysplastic syndrome was higher in the MYD88WT cohort (16% versus 4% in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease‐defining feature in WM. Our findings warrant external validation, preferably through prospective studies.