Worth a Double Take? An In-Depth Review of Lung Retransplantation.

Provided advancements in Lung Transplantation (LT) survival, the efficacy of Lung Retransplantation (LRT) has often been debated. Decades of retrospective analyses on thousands of LRT cases provide insight enabling predictive patient criteria for retransplantation. This review used the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. The PubMed search engine was utilized for articles relating to LRT published through August 2023, and a systematic review was performed using Covidence software version 2.0 (Veritas Health Innovation, Australia). Careful patient selection is vital for successful LRT, and the benefit leans in favor of those in optimal health following their initial transplant. However, the lack of a standardized approach remains apparent. Through an in-depth review, we will address considerations such as chronic lung allograft dysfunction, timing to LRT, surgical and perioperative complexity, and critical ethical concerns that guide the current practice as it relates to this subset of patients for whom LRT is the only therapeutic option available.

The Evaluation and Management of Coronary Artery Disease in the Lung Transplant Patient.

Lung transplantation can greatly improve quality of life and extend survival in those with end-stage lung disease. In order to derive the maximal benefit from such a procedure, patients must be carefully selected and be otherwise healthy enough to survive a high-risk surgery and sometimes prolonged immunosuppressive therapy following surgery. Patients therefore must be critically assessed prior to being listed for transplantation with close attention paid towards assessment of cardiovascular health and operative risk. One of the biggest dictators of this is coronary artery disease. In this review article, we discuss the assessment and management of coronary artery disease in the potential lung transplant candidate.

Single Lung Transplant for Secondary Pulmonary Hypertension: The Right Option for the Right Patient.

Introduction: The optimal treatment for Secondary Pulmonary Hypertension from End-Stage Lung Disease remains controversial. Double Lung Transplantation is widely regarded as the treatment of choice as it eliminates all diseased parenchyma and introduces a large volume of physiologically normal allograft. By comparison, the role of single lung transplantation for pulmonary hypertension (PAH) is less clear. The remaining diseased lung will limit clinical improvements and permit downstream sequelae; including residual cough, recurrent infection, and continued pulmonary hypertension. But not every patient can undergo DLT. Advanced age, frailty, co-morbid conditions, and limited availability of organs will all affect surgical candidacy and can offset the benefits of double lung procedures. Studies that compare SLT and DLT do not commonly explore the utility of single lung procedures even though multiple theoretical advantages exist; including reduced waiting times, less waitlist mortality, fewer surgical complications, and lower operative mortality. Worse, multiple forms of publication and selection bias may favor DLT in registry-based studies. In this review, we present the prevailing literature on single and double lung transplants in patients with secondary pulmonary hypertension and clarify the potential utility of these procedures. Materials and Methods: A PubMed search for English-language articles exploring single and double lung transplants in the setting of secondary pulmonary hypertension was conducted from 1990 to 2023. Key words included "single lung transplant", "double lung transplant", "pulmonary hypertension", "rejection", "complications", "extracorporeal membranous oxygenation", "death", and all appropriate Boolean operators. We prioritized research from retrospective studies that evaluated clinical outcomes from single centers. Conclusions: The question is not whether DLT is better at resolving lung disease; instead, we must ask if SLT is an acceptable form of therapy in a select group of high-risk patients. Further research should focus on how best to identify recipients that may benefit from each type of procedure, and the clinical utility of perioperative VA ECMO.

Intraoperative Extracorporeal Support during Lung Transplantation: Not Just for the High-Risk Patient.

The use of intraoperative mechanical support during lung transplantation has traditionally been a controversial topic. Trends for intraoperative mechanical support strategies swing like a pendulum. Historically, cardiopulmonary bypass (CPB) was the modality of choice during transplantation. It provides full hemodynamic support including oxygenation and decarboxylation. Surgical exposure is improved by permitting the drainage of the heart and provides more permissive retraction. CPBs contain drainage reservoirs with hand-held pump suction catheters promoting blood conservation through collection and re-circulation. But CPB has its disadvantages. It is known to cause systemic inflammation and coagulopathy. CPB requires high doses of heparinization, which increases bleeding risks. As transplantation progressed, off-pump transplantation began to trend as a preferable option. ECMO, however, has many of the benefits of CPB with less of the risk. Outcomes were improved with ECMO compared to CPB. CPB has a higher blood transfusion requirement, a higher need for post-operative ECMO support, a higher re-intubation rate, high rates of kidney injury and need for hemodialysis, longer ICU stays, higher incidences of PGD grade 3, as well as overall in-hospital mortality when compared with ECMO use. The focus now shifts to using intraoperative mechanical support to protect the graft, helping to reduce ischemia-reperfusion injury and allowing for lung protective ventilator settings. Studies show that the routine use of ECMO during transplantation decreases the rate of primary graft dysfunction and many adverse outcomes including ventilator time, need for tracheostomy, renal failure, post-operative ECMO requirements, and others. As intraoperative planned ECMO is considered a safe and effective approach, with improved survival and better overall outcomes compared to both unplanned ECMO implementation and off-pump transplantation, its routine use should be taken into consideration as standard protocol.

Measuring the margin distance in pulmonary wedge resection.

BACKGROUND: Margin distance contributes to survival and recurrence during wedge resections for early-stage non-small cell lung cancer. The Initiative for Early Lung Cancer Research on Treatment sought to standardize a surgeon-measured margin intraoperatively. METHODS: Lung cancer patients who underwent wedge resection were reviewed. Margins were measured by the surgeon twice as per a standardized protocol. Intraobserver variability as well as surgeon-pathologist variability were compared. RESULTS: Forty-five patients underwent wedge resection. Same-surgeon measurement analysis indicated good reliability with a small mean difference and narrow limit of agreement for the two measures. The median surgeon-measured margin was 18.0 mm, median pathologist-measured margin was 16.0 mm and the median difference between the surgeon-pathologist margin was -1.0 mm, ranging from -18.0 to 12.0 mm. Bland-Altman analysis for margin measurements demonstrated a mean difference of 0.65 mm. The limit of agreement for the two approaches were wide, with the difference lying between -16.25 and 14.96 mm. CONCLUSIONS: A novel protocol of surgeon-measured margin was evaluated and compared with pathologist-measured margin. High intraobserver agreement for repeat surgeon measurements yet low-to-moderate correlation or directionality between surgeon and pathologic measurements were found. DISCUSSION: A standardized protocol may reduce variability in pathologic assessment. These findings have critical implications considering the impact of margin distance on outcomes.

Acute Lower Extremity Ischemia Following Thoracotomy Owing to Arterial Tumor Emboli.

Our patient is a 58-year-old woman with metastatic uterine leiomyosarcoma with prior resection found to have an isolated metastatic lesion in the upper lobe of the right lung. She underwent a thoracotomy with right upper and middle lobectomy. After her procedure, she developed acute ischemia of her left lower extremity secondary to an embolized tumor. The patient was treated with thrombectomy and fasciotomy, and she recovered without loss of function of the limb. A literature review demonstrates that acute limb ischemia secondary to tumor emboli remains a rare but potentially devastating complication of metastatic disease.

Distracting injury defined: does an isolated hip fracture constitute a distracting injury for clearance of the cervical spine?

OBJECTIVES: As the population within the USA ages, the number of hip fractures seen yearly in the emergency department is expected to rise. According to the NEXUS criteria, many of these patients receive computerized tomographic scan (CT) evaluation of the cervical spine because a hip fracture may constitute a distracting injury. The objective of this study is to determine if an isolated hip fracture constitutes a distracting injury which requires imaging of the cervical spine. METHODS: Data were prospectively collected on 158 trauma patients with isolated hip fractures between April 1, 2015 and March 9, 2016. Patient demographics were analyzed and compared to the National Emergency X-Radiography Utilization Study (NEXUS). RESULTS: Patients with isolated hip fractures were predominantly elderly, on average 78.6 +/- 15.9 years old, and 94.3% of these injuries occurred after a fall from standing. Only one patient also had a cervical spine fracture which was not clinically significant. When compared to the established rate of cervical spine injury of 2.4%, the absolute risk reduction (ARR) was 0.35% (95% CI, - 1.06 to 1.75%) and the number needed to treat (NNT) was 290. CONCLUSION: In the case of an elderly patient with an isolated hip fracture and no cervical midline tenderness, cervical spine imaging may be reserved for those who have other NEXUS criteria for further workup.

Temporary targeted renal blood flow interruption using a reverse thermosensitive polymer to facilitate bloodless partial nephrectomy: a swine survival study.

UNLABELLED: What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. OBJECTIVE: To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. MATERIALS AND METHODS: A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. RESULTS: All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. CONCLUSION: Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue.

Targeted endovascular temporary vessel occlusion with a reverse thermosensitive polymer for near-bloodless partial nephrectomy: comparison to standard surgical clamping techniques.

PURPOSE: To determine whether reversible blood flow interruption to a randomly chosen target region of the kidney may be achieved with the injection of a reverse thermoplastic polymer through an angiographic catheter, thereby facilitating partial nephrectomy without compromising blood flow to the remaining kidney or adding risks beyond those encountered by the use of hilar clamping. METHODS: Fifteen pigs underwent partial nephrectomy after blood flow interruption by vascular cross-clamping or injection of polymer (Lumagel™) into a segmental artery. Five animals were euthanized after surgery (three open and two laparoscopic resection, cross-clamping n = 2), and 10 (open resection, cross-clamping n = 4) were euthanized after 6 weeks' survival. Blood specimens were obtained periodically, and angiogram and necropsy were performed at 6 weeks. RESULTS: Selective renal ischemia was achieved in all cases. Surgical resection time averaged 9 and 24.5 min in the open and laparoscopic groups, respectively. Estimated blood loss was negligible with the exception of one case where an accessory renal artery was originally overlooked. Reversal of the polymer to a liquid state was consistent angiographically and visually in all cases. Time to complete flow return averaged 7.4 and 2 min for polymer and clamping, respectively. Angiography at 6 weeks revealed no evidence of vascular injury. Laboratory data and necropsies revealed no differences between animals undergoing vascular clamping or polymer injection. CONCLUSION: Lumagel was as effective as vascular clamping in producing a near bloodless operative field for partial nephrectomy while maintaining flow to the uninvolved portion of the affected kidney.

Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica.

RATIONALE: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. OBJECTIVES: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. METHODS: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. MEASUREMENTS AND MAIN RESULTS: Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log(10) unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05-0.67; P = 0.01), and increased airway responsiveness (a < or =8.58-mumol provocative dose of methacholine producing a 20% fall in baseline FEV(1) [OR, 0.15; 95% CI, 0.024-0.97; P = 0.05]). CONCLUSIONS: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.

Diversity of the gut microbiota and eczema in early life.

BACKGROUND: A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results. OBJECTIVE: To examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture. METHODS: Fecal samples were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool samples, we compared the microbial diversity of cases and controls using the number of electrophoretic bands and the Shannon index of diversity (H') as indicators. RESULTS: Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in diversity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32). CONCLUSION: Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life.

Paternal asthma, mold exposure, and increased airway responsiveness among children with asthma in Costa Rica.

BACKGROUND: Little is known about the determinants of airway hyperresponsiveness (AHR) among children with asthma in Hispanic America. METHODS: We examined the relations among selected familial and environmental factors, markers of allergy, spirometric measures of lung function, and AHR in a cross-sectional study of 403 Costa Rican children with asthma between the ages of 6 and 14 years. Study participants completed a protocol that included questionnaires, spirometry, measurements of serum total and allergen-specific IgE, peripheral blood eosinophil count, and body mass index, and the assessment of airway responsiveness to methacholine (ie, a methacholine challenge test [MCT]). AHR to MCT was defined as the provocative dose of methacholine causing a 20% fall in FEV(1). Linear regression was used for the univariate and multivariate analyses. RESULTS: Of the 403 asthmatic children who underwent an MCT, 350 (86.8%) had AHR to methacholine. In a multivariate analysis, paternal asthma (p = 0.004), parental report of mold/mildew in the child's home (p = 0.04), FEV(1)/FVC ratio (p < 0.0001), and a positive IgE response to Der p 1 (p = 0.008) were significantly associated with AHR among Costa Rican children with asthma. CONCLUSION: Our results suggest that paternal asthma and environmental exposure to mold/mildew are strong determinants of AHR in Costa Rican children with asthma. FEV(1)/FVC ratio may be a useful measure of AHR (a marker of asthma severity) among Costa Ricans and other Hispanic Americans for whom reference values for FEV(1) are not currently available.

Mode of delivery and cord blood cytokines: a birth cohort study.

BACKGROUND: The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. OBJECTIVE: To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora). METHODS: CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-gamma, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients. RESULTS: Cesarean section was associated with increased levels of IL-13 and IFN-gamma. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P < 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-gamma. CONCLUSION: Cesarean section is associated with increased levels of IL-13 and IFN-gamma, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.