In patients with OSA and CVD, CPAP did not reduce major adverse cardiac and cerebrovascular events.

SOURCE CITATION: Sanchez-de-la-Torre M, Gracia-Lavedan E, Benitez ID, et al. Adherence to CPAP treatment and the risk of recurrent cardiovascular events: a meta-analysis. JAMA. 2023;330:1255-1265. 37787793.

VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients.

BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19. OBJECTIVE: To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19. METHODS: Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT). RESULTS: The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement. CONCLUSION: VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.

Respiratory recovery trajectories after severe-to-critical COVID-19: a 1-year prospective multicentre study.

BACKGROUND: Survivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life. METHODS: Adults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study. RESULTS: Among 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (D LCO) and significant radiological sequelae, respectively. During extended follow-up, both D LCO and forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated with D LCO at 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images. CONCLUSIONS: Although pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Plasma ratio of angiopoietin-2 to angiopoietin-1 is a biomarker of vascular impairment in chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) patients have an increased risk of cardiovascular disease. Muscle biopsies have revealed that the muscle vasculature in COPD patients was characterized by a capillary rarefaction with reduced pericyte coverage. Thus, an imbalance of the plasma Angiopoietin-1 / Angiopoietin-2 (Ang2/Ang1) ratio could constitute a non-invasive marker of the muscle vascular impairment. In 14 COPD patients (65.5±5.1-year-old) and 7 HC (63.3±5.8-year-old), plasma samples were obtained at 3 time-points: before, after 5 weeks (W5), and after 10 weeks (W10) of exercise training. COPD patients showed a muscle capillary rarefaction at baseline with a reduced capillary coverage at W5 and W10. The plasma Ang2/Ang1 ratio was significantly higher in COPD patients vs. HC during the training (Group: p=0.01). The plasma Ang2/Ang1 ratio was inversely correlated with the pericyte coverage index regardless of the time period W0 (r=-0.51; p=0.02), W5 (r=-0.48; p=0.04), and W10 (r=-0.61; p<0.01). Last, in ECFC/MSC co-cultures exposed to the W10 serum from COPD patients and HC, the plasma Ang2/Ang1 at W10 were inversely correlated with calponin staining (r=-0.64. p=0.01 and r= 0.71. p<0.01, Fig. 1B), in line with a role of this plasma Ang2/Ang1 in the MSC differentiation into pericytes. Altogether, plasma Ang2/Ang1 ratio could constitute a potential marker of the vascular impairment in COPD patients.

Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation.

BACKGROUND: Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic BMPR2 mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomatic BMPR2 mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population. METHODS: Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study; ClinicalTrials.gov: NCT01600898). Annual screening included clinical assessment, ECG, pulmonary function tests, 6-min walk distance, cardiopulmonary exercise testing, chest radiography, echocardiography and brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP level. Right heart catheterisation (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline. RESULTS: 55 subjects (26 males; median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT-proBNP levels. All subjects accepted RHC at inclusion, which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension (21.8%). At long-term follow-up (118.8 patient-years of follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2.3% per year (0.99% per year in males and 3.5% per year in females). All PAH cases remained at low-risk status on oral therapy at last follow-up. CONCLUSIONS: Asymptomatic BMPR2 mutation carriers have a significant risk of developing incident PAH. International multicentre studies are needed to confirm that refined multimodal screening programmes with regular follow-up allow early detection of PAH.

Economizing the Septal Cartilage for Grafts During Rhinoplasty, 40 Years' Experience.

BACKGROUND: During rhinoplasty, it is typically necessary to use cartilage to shape and support the final nasal construct to provide both form and function to the nose (Tanna et al. in Plast Reconstr Surg 141(1):137e-151e, 2018; Guyuron in Plast Reconstr Surg 105(6):2257-2259, 2000; Kim et al. in Ann Plast Surg 65(6):519-523, 2010). The septal cartilage is the ideal graft both for its ease of access and quality of cartilage. However, this graft is a limited resource, and economy of its use is important as to negate the need to harvest cartilage from the ear or rib. THE PURPOSE: 1. To share the senior author's 40 years' experience with the economy of septal cartilage. 2. To identify the areas of the septal cartilage most suitable for a particular graft. 3. To discuss the common grafts that are used in rhinoplasty. 4. To identify when other sources of cartilage are needed and where to best use those grafts. 5. To present option for preservation of the leftover septal cartilage. CONCLUSION: Overall consideration should focus on the size, thickness, and curvature of the graft contemplating the structural and functional needs of the rhinoplasty maneuvers. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Understanding the Similarities and Differences between Hepatic and Pulmonary Veno-Occlusive Disease.

Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). Similarly, PVOD can develop after exposure to chemotherapeutic agents in the treatment of solid and hematological malignancies. In addition, PVOD has also been linked to autoimmune disorders and occupational solvent exposure. Finally, the heritable form of PVOD is due to biallelic mutations of the EIF2AK4 gene. Both HVOD and PVOD share common histopathological features and pathophysiologic mechanisms. Both clinical disorders are rare complications that can appear after exposure to the common inciting trigger of chemotherapeutic agents. The present review aims to summarize the current knowledge of HVOD and PVOD and to describe both similarities as well as differences regarding both conditions.

Improving Care of Cleft-Related Velopharyngeal Incompetence on Humanitarian Missions Using a Multidisciplinary Team Approach.

BACKGROUND: Proper evaluation and analysis of speech surgery outcomes for cleft-related velopharyngeal incompetence in children and young adults performed on humanitarian missions is poorly characterized. The aim of this study is to examine the effect of using a multidisciplinary team on cleft-related humanitarian missions. The effect on patient selection, velopharyngeal mechanism imaging, and speech outcomes after surgery will be highlighted. METHODS: A review of the Medical Readiness Training Exercise database for craniofacial missions to the Dominican Republic from 2009 to 2011 was performed. A speech pathologist and a craniofacial surgeon evaluated all patients with a diagnosis of cleft palate and speech abnormalities. Patients were screened using speech analysis and selective nasal endoscopy. Data collected included sex, age, diagnosis, speech scores, date, and type of surgical procedure-that is, pharyngeal flap (PF) versus sphincter pharyngoplasty (SP), morbidity, and mortality. RESULTS: One hundred twenty-six patients with cleft palate were screened during the study period by a craniofacial surgeon and secondarily by a speech pathologist. Twenty-eight patients were identified with nasal quality speech of whom 12 patients (12/126 = 9.5% of total surgical cases) underwent PF/SP surgery after previous primary repair of a cleft palate defect. The 16 remaining patients (16/28 = 57%) with nonsurgical speech abnormalities were determined that surgery was not going to be beneficial and they were spared unnecessary surgery after speech pathology evaluation and nasal endoscopy. Eight patients were female and 4 patients were male; average age was 13.3 years (range 4-27 years). Seven pharyngeal flaps (58%) and 5 (42%) sphincter pharyngoplasty procedures were performed. The average presurgical speech score was 11.4 (range 6-24). There was a significant decrease in postsurgical speech scores with the average postsurgical speech score of 5.2 (range 0-21, P value = 0.0028). Follow-up evaluation averaged 18 months (range 6-24). Average hospital stay was 2 days for PF/SP surgery. Two patients, both with developmental delay, retained speech scores greater than 6. There were no major complications or reoperations. CONCLUSIONS: Pharyngeal flap/sphincter pharyngoplasty surgery in young adults resulted in improved speech scores and comprehensibility after speech surgery on Medical Readiness Training Exercise military humanitarian missions. Speech surgery in older patients in relatively austere environments is safe and effective. After comprehensive multidisciplinary team evaluation, 43% of the patients who were screened to have velopharyngeal incompetence were identified as surgical candidates. Fifty-seven percent of patients evaluated by speech pathologist were recommend nonsurgical solution toward improving speech scores sparing them unnecessary surgery. The incorporation of a speech pathologist to the humanitarian mission resulted in identifying surgical candidates who would benefit the most from intervention and improved speech surgery outcomes.

A nonstop variant in REEP1 causes peripheral neuropathy by unmasking a 3'UTR-encoded, aggregation-inducing motif.

Single-nucleotide variants that abolish the stop codon ("nonstop" alterations) are a unique type of substitution in genomic DNA. Whether they confer instability of the mutant mRNA or result in expression of a C-terminally extended protein depends on the absence or presence of a downstream in-frame stop codon, respectively. Of the predicted protein extensions, only few have been functionally characterized. In a family with autosomal dominant Charcot-Marie-Tooth disease type 2, that is, an axonopathy affecting sensory neurons as well as lower motor neurons, we identified a heterozygous nonstop variant in REEP1. Mutations in this gene have classically been associated with the upper motor neuron disorder hereditary spastic paraplegia (HSP). We show that the C-terminal extension resulting from the nonstop variant triggers self-aggregation of REEP1 and of several reporters. Our findings support the recently proposed concept of 3'UTR-encoded "cryptic amyloidogenic elements." Together with a previous report on an aggregation-prone REEP1 deletion variant in distal hereditary motor neuropathy, they also suggest that toxic gain of REEP1 function, rather than loss-of-function as relevant for HSP, specifically affects lower motor neurons. A search for similar correlations between genotype, phenotype, and effect of mutant protein may help to explain the wide clinical spectra also in other genetically determined disorders.

RV Fractional Area Change and TAPSE as Predictors of Severe Right Ventricular Dysfunction in Pulmonary Hypertension: A CMR Study.

BACKGROUND: The right ventricular ejection fraction (RVEF) is a surrogate marker of right ventricular function in pulmonary hypertension (PH), but its measurement is complicated and time consuming. The tricuspid annular plane systolic excursion (TAPSE) measures only the longitudinal component of RV contraction while the right ventricular fractional area change (RVFAC) takes into account both the longitudinal and the transversal components. The aim of our study was to evaluate the relationship between RVEF, RVFAC, and TAPSE according to hemodynamic severity in two groups of patients with PH: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: Fifty-four patients with PAH (n = 15) and CTEPH (n = 39) underwent right heart catheterization and cardiac magnetic resonance (CMR). The ventricular volumes and areas, TAPSE, and eccentricity index were measured. The RVFAC was more strongly correlated with the RVEF (r = 0.81, p < 0.0001) than the TAPSE (r = 0.63, p < 0.0001). RVEF < 35% was better predicted by the RVFAC than the TAPSE (TAPSE: AUC = 0.77 and RVFAC: AUC = 0.91; p = 0.042). In the group with the worse hemodynamic status, the RVFAC correlated much better with the RVEF than the TAPSE. There were no significant differences in the CMR data analyzed between the groups of PAH and CETPH patients. CONCLUSIONS: The RVFAC is a good index to estimate RVEF in PH patients; even better than the TAPSE in patients with more severe hemodynamic profile, possibly for including the transversal component of right ventricular function in its measurement. Furthermore, RVFAC performance was similar in the two PH groups (PAH and CTEPH).

Macrophage Migration Inhibitory Factor (MIF) Inhibition in a Murine Model of Bleomycin-Induced Pulmonary Fibrosis.

BACKGROUND: Pulmonary hypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that significantly contributes to morbidity and mortality. Macrophage migration inhibitory factor (MIF) is a critical factor in vascular remodeling of the pulmonary circulation. OBJECTIVES: We tested the effects of two small molecules targeting MIF on bleomycin (BLM)-induced collagen deposition, PH, and vascular remodeling in mouse lungs. METHODS: We examined the distribution pattern of MIF, CD74, and CXCR4 in the lungs of patients with IPF-PH and the lungs of BLM-injected mice. Then, treatments were realized with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and N-(3-hydroxy-4-fluorobenzyl)-5 trifluoromethylbenzoxazol-2-thione 31 (20 mg/kg/day per os for 3 weeks) started 24 h after an intratracheal BLM administration. RESULTS: More intense immunoreactivity was noted for MIF, CD74, and CXCR4 in lungs from IPF-PH patients and BLM-injected mice. Furthermore, we found that treatments of BLM-injected mice with ISO-1 or compound 31 attenuated lung collagen deposition and right ventricular systolic pressure increase. Additionally, reduced pulmonary inflammatory infiltration and pulmonary arterial muscularization were observed in the lungs of BLM-injected mice treated with ISO-1 or compound 31. CONCLUSIONS: Treatments with ISO-1 or compound 31 attenuates BLM-induced inflammation and fibrosis in lung, and prevents PH development in mice, suggesting that MIF is an important factor for IPF-PH development.

Non-invasive diagnosis of pulmonary hypertension from lung Doppler signal: a proof of concept study.

Transthoracic Parametric Doppler (TPD) is a novel ultrasound technique recently developed for the investigation of pulmonary blood vessels. Lung Doppler Signals (LDS) recorded from TPD provide information regarding the functional mechanical characteristics of pulmonary blood vessels. We aimed to define the specific profile of LDS generated from TPD imaging in patients with pulmonary hypertension (PH), and to evaluate the diagnostic performance of LDS to detect PH using right heart catheterization (RHC) as gold standard reference. Seventy nine PH patients and 79 healthy controls matched for age, gender and BMI were recruited in a prospective case-control multicenter study. LDS recordings were performed by TPD consisting of a pulsed Doppler with a 2 MHz single element transducer. LDS were recorded within 24 h of RHC. Following LDS extraction, classification and performance evaluation were performed offline using a support vector machine (k-fold cross validation method). The best LDS parameters for PH detection were (1) peak velocity of the systolic (S) and diastolic (D) signals, (2) the rise slope of the S and D signals, and (3) time to peak of the S signal. Overall, the sensitivity and specificity of TPD for detection of PH were 82.7 % (95 % CI 81.3-84.1) and 87.4 % (95 % CI 86.3-88.5), respectively, with an area under the receiver operating curve of 0.95 (95 % CI 0.94-0.96). Detection rate of PH increased progressively with the level of mean pulmonary artery pressure. LDS recorded by TPD display a specific profile in PH and appears to be a promising and reliable tool for PH diagnosis. Further studies are required to confirm the clinical usefulness of LDS.

High Frequency of Pathogenic Rearrangements in SPG11 and Extensive Contribution of Mutational Hotspots and Founder Alleles.

Biallelic loss-of-function mutations in SPG11 cause a wide spectrum of recessively inherited, neurodegenerative disorders including hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease. By comprehensive screening of three large cohorts of HSP index patients, we identified 83 alleles with "small" mutations and 13 alleles that carry large genomic rearrangements. Including relevant data from previous studies, we estimate that copy number variants (CNVs) account for ∼19% of pathogenic SPG11 alleles. The breakpoints for all novel and some previously reported CNVs were determined by long-range PCR and sequencing. This revealed several Alu-associated recombination hotspots. We also found evidence for additional mutational mechanisms, including for a two-step event in which an Alu retrotransposition preceded the actual rearrangement. Apparently independent samples with identical breakpoints were analyzed by microsatellite PCRs. The resulting haplotypes suggested the existence of two rearrangement founder alleles. Our findings widen the spectra of mutations and mutational mechanisms in SPG11, underscore the pivotal role played by Alus, and are of high diagnostic relevance for a wide spectrum of clinical phenotypes including the most frequent form of recessive HSP.

Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia.

Hereditary spastic paraplegias (HSPs) are genetically and clinically heterogeneous axonopathies primarily affecting upper motor neurons and, in complex forms, additional neurons. Here, we report two families with distinct recessive mutations in TFG, previously suggested to cause HSP based on findings in a single small family with complex HSP. The first carried a homozygous c.317G>A (p.R106H) variant and presented with pure HSP. The second carried the same homozygous c.316C>T (p.R106C) variant previously reported and displayed a similarly complex phenotype including optic atrophy. Haplotyping and bisulfate sequencing revealed evidence for a c.316C>T founder allele, as well as for a c.316_317 mutation hotspot. Expression of mutant TFG proteins in cultured neurons revealed mitochondrial fragmentation, the extent of which correlated with clinical severity. Our findings confirm the causal nature of bi-allelic TFG mutations for HSP, broaden the clinical and mutational spectra, and suggest mitochondrial impairment to represent a pathomechanistic link to other neurodegenerative conditions.

Mitomycin-Induced Pulmonary Veno-Occlusive Disease: Evidence From Human Disease and Animal Models.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension characterized by the obstruction of small pulmonary veins and a dismal prognosis. PVOD may be sporadic or heritable because of biallelic mutations of the EIF2AK4 gene coding for GCN2. Isolated case reports suggest that chemotherapy may be a risk factor for PVOD. METHODS AND RESULTS: We reported on the clinical, functional, and hemodynamic characteristics and outcomes of 7 cases of PVOD induced by mitomycin-C (MMC) therapy from the French Pulmonary Hypertension Registry. All patients displayed squamous anal cancer and were treated with MMC alone or MMC plus 5-fluoruracil. The estimated annual incidence of PVOD in the French population that have anal cancer is 3.9 of 1000 patients, which is much higher than the incidence of PVOD in the general population (0.5/million per year). In rats, intraperitoneal administration of MMC induced PVOD, as demonstrated by pulmonary hypertension at right-heart catheterization at days 21 to 35 and major remodeling of small pulmonary veins associated with foci of intense microvascular endothelial-cell proliferation of the capillary bed. In rats, MMC administration was associated with dose-dependent depletion of pulmonary GCN2 content and decreased smad1/5/8 signaling. Amifostine prevented the development of MMC-induced PVOD in rats. CONCLUSIONS: MMC therapy is a potent inducer of PVOD in humans and rats. Amifostine prevents MMC-induced PVOD in rats and should be tested as a preventive therapy for MMC-induced PVOD in humans. MMC-induced PVOD in rats represents a unique model to test novel therapies in this devastating orphan disease.

Resting pulmonary artery pressure of 21-24†mmHg predicts abnormal exercise haemodynamics.

A resting mean pulmonary artery pressure (mPAP) of 21-24 mmHg is above the upper limit of normal but does not reach criteria for the diagnosis of pulmonary hypertension (PH). We sought to determine whether an mPAP of 21-24 mmHg is associated with an increased risk of developing an abnormal pulmonary vascular response during exercise.Consecutive patients (n=290) with resting mPAP <25 mmHg who underwent invasive exercise haemodynamics were analysed. Risk factors for pulmonary vascular disease or left heart disease were present in 63.4% and 43.8% of subjects. An abnormal pulmonary vascular response (or exercise PH) was defined by mPAP >30 mmHg and total pulmonary vascular resistance >3 WU at maximal exercise.Exercise PH occurred in 74 (86.0%) out of 86 versus 96 (47.1%) out of 204 in the mPAP of 21-24 mmHg and mPAP <21 mmHg groups, respectively (OR 6.9, 95% CI: 3.6-13.6; p<0.0001). Patients with mPAP of 21-24 mmHg had lower 6-min walk distance (p=0.002) and higher New York Heart Association functional class status (p=0.03). Decreasing levels of mPAP were associated with a lower prevalence of exercise PH, which occurred in 60.3%, 38.7% and 7.7% of patients with mPAP of 17-20, 13-16 and <13 mmHg, respectively.In an at-risk population, a resting mPAP between 21-24 mmHg is closely associated with exercise PH together with worse functional capacity.

Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents.

Body Image & Quality of Life: Changes With Gastric Bypass and Body Contouring.

INTRODUCTION: Bariatric surgery has emerged as an effective method of combating the morbid obesity epidemic. However, the massive weight loss that follows may result in contour changes that can affect body image and quality of life. Our study examines the effects and consequences of bariatric surgery and subsequent body contouring on body image and quality of life. METHODS: Patients were prospectively followed up through their experience with bariatric surgery and subsequent body contouring surgery. Using 2 validated survey instruments, the Multidimensional Body-Self Relations Questionnaire and the Short Form 36 (SF-36), patients completed questionnaires preoperatively and at 6, 12, and 24 months postoperatively. Mean scores were determined by repeated measures analyses of variance F tests. RESULTS: One hundred seventy-five patients were surveyed before bariatric surgery, with noted declines in survey completion at 6, 12, and 24 months. Appearance Evaluation scores improved significantly at all intervals (P = 0.0033), as did Body Area Satisfaction Scale and Appearance Orientation scores (P = 0.0079 and P = 0.044, respectively). While Overweight Preoccupation and Self-Classified Weight scores decreased over time, only the latter was significant (P < 0.0001). The composite SF-36 score for patients awaiting bariatric surgery (54.1%) with postoperative scores at 6 (67.6%,), 12 (at 74.0%), and 24 (76.7%) months being significantly higher (P < 0.0001). The body contouring group consisted of 41 patients who primarily had lower body procedures, with 31 patients surveyed at 6 months and 27 patients at 12 months. For this cohort, Appearance Evaluation and Body Area Satisfaction Scale scores both improved significantly (P = 0.0001 and P = 0.0005, respectively) whereas Appearance Orientation scores declined significantly (P = 0.0055). Both Overweight Preoccupation and Self-Classified Weight scores decreased with only the latter being statistically significant (P = 0.0286). Postoperative SF-36 scores at 6 (72.9%) and 12 (64.5%) months were no different than patients awaiting body contouring (71.3%). CONCLUSIONS: Using 2 validated survey instruments, we show that patients undergoing bariatric surgery have improvements in body image and quality of life. Subsequent postbariatric body contouring surgery results in further improvements in body image. Our findings provide measurable evidence for the value of body contouring after significant weight loss, which may favor greater insurance coverage for this patient population.

Criteria for diagnosis of exercise pulmonary hypertension.

The previous definition of exercise pulmonary hypertension (PH) with a mean pulmonary artery pressure (mPAP) >30 mmHg was abandoned because healthy individuals can exceed this threshold at high cardiac output (CO). We hypothesised that incorporating assessment of the pressure-flow relationship using the mPAP/CO ratio, i.e. total pulmonary resistance (TPR), might enhance the accuracy of diagnosing an abnormal exercise haemodynamic response.Exercise haemodynamics were evaluated in 169 consecutive subjects with normal resting mPAP ≤20 mmHg. Subjects were classified into controls without heart or lung disease (n=68) versus patients with pulmonary vascular disease (PVD) (n=49) and left heart disease (LHD) (n=52).TPR and mPAP at maximal exercise produced diagnostic accuracy with area under the receiver operating curve of 0.99 and 0.95, respectively, for discriminating controls versus patients with PVD and LHD. The old criterion of mPAP >30 mmHg had sensitivity of 0.98 but specificity of 0.77. Combining maximal mPAP >30 mmHg and TPR >3 mmHg·min·L(-1) retained sensitivity at 0.93 but improved specificity to 1.0. The accuracy of the combined criteria was high across different age groups, sex, body mass index and diagnosis (PVD or LHD).Combining mPAP >30 mmHg and TPR >3 mmHg·min·L(-1) is superior to mPAP >30 mmHg alone for defining a pathological haemodynamic response of the pulmonary circulation during exercise.

Rise in microsurgical free-flap breast reconstruction in academic medical practices.

BACKGROUND: Previous studies have examined national trends in breast reconstruction, using various data sets demonstrating increases in implant-based reconstruction and decreases in autologous reconstruction. However, academic breast reconstruction practices have never been specifically characterized. The University Health Consortium-Association of American Medical Colleges Faculty Practice Solutions Center database contains comprehensive, factual billing and coding data from 90 academic medical centers in the United States, and has been used to characterize practice patterns of various academic surgical specialties. OBJECTIVE: To describe breast reconstruction trends unique to academic surgical practices, using the Faculty Practice Solutions Center database. METHODS: Annual data for defined breast reconstruction procedures (current procedural terminology codes: 19340, 19342, 19357, 19361, 19364, 19366, 19367, 19369, and 19380) performed by university plastic surgeons during calendar years 2007 to 2013 were included in the study. RESULTS: From 2007 to 2013, a 2-fold increase in the number of breast reconstruction procedures was observed (from a mean of 45.3 to 94.2 procedures per surgeon). During this period, implant-based reconstructions and autologous reconstructions rose in tandem (28.9-44.6 and 11.4-19.3, respectively), with a preserved 2.5:1 ratio between the 2 categories each year. When compared to reconstructions overall, the proportion of both implant reconstruction and autologous reconstruction procedures declined, since revision and other types of reconstructions increased (11% of all reconstructions in 2007 vs 32% in 2013). With regard to autologous reconstruction, microsurgical free flaps (mostly comprised of deep inferior epigastric artery perforator flaps) have supplanted latissimus flaps as the favored modality and comprised 13% to 14% of breast reconstruction cases overall from 2011 to 2013. CONCLUSION: In contrast to national trends, university-based plastic surgeons are performing a growing number of microsurgical free flaps as the preferred method for autologous breast reconstruction. Whereas implant-based reconstructions still predominate in academic practices, the trend of increasing preference toward implant-based reconstructions has slowed in recent years and revision reconstructions are on the rise.