Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns.

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.

The correlation between occupation type and fibromyalgia severity.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disorder associated with financial burden, decreased work productivity and absenteeism. Occupational stressors and specific employment factors may contribute to the severity of FM. AIMS: To determine if occupation type or employment status correlates with FM diagnostic and severity parameters, as assessed via validated instruments including tender points (TP), Widespread Pain Index (WPI), Symptom Severity (SS) and pain regions. METHODS: We performed a cross-sectional study of 200 adult patients diagnosed with FM at a single-centre FM clinic. Demographic and clinical data were extracted from the electronic medical records. Occupations were manually grouped in an iterative modified-Delphi approach and participants were grouped by employment status (Working, Not Working/Disabled or Retired) for analysis. RESULTS: In our cohort, 61% were employed and 24% were not working/disabled, while the remainder were students, homemakers or retired. SS score was significantly higher (P < 0.001) in not working/disabled patients compared to those employed. Business owners had the lowest TP count (median = 14) and the lowest median SS score (median = 7). WPI was highest for Others (Arts/Entertainment, Driver/Delivery and Housekeeper/Custodian workers; median=16) and the lowest for Retail/Sales/Wait Staff (median = 11). CONCLUSIONS: Work-related factors, occupation type and employment status correlate with diagnostic and severity parameters of FM. Employed participants had significantly lower SS scores suggesting that work loss correlates with SS. Participants employed in entry-level jobs or jobs with higher physical or financial stressors may experience greater FM symptoms. Further studies are required to explore work-related factors and their impact on the diagnostic and severity parameters of FM.

Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors.

BACKGROUND: Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors. METHODS: Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630 nm wavelength) was applied at 200 J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study). RESULTS: There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%. CONCLUSION: PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.

Photodynamic therapy to a primary cancer of the peripheral lung: Case report.

Photodynamic therapy (PDT) is an FDA approved treatment for lung cancer. In the United States the photosensitizer porfimer sodium (Photofrin®, Pinnacle Biologics) is intravenously introduced at 2mg/kg. After approximately 48 h, illumination to activate the photosensitizer is initiated, with 630nm red light at 200J/cm, delivered by fiber-optic catheter, brought to the tumor endo- bronchially, and delivered for 500 s. This will create, in the presence of oxygen, a Type II Photodynamic Reaction (PDR) which generates singlet oxygen species that are tumor ablative. Classically, PDT for lung cancer has been employed for symptomatic central and obstructing tumors with great success. This case report describes an innovative approach to treat a peripheral, early stage lung cancer employing magnetic navigation and endobronchial treatment. We report on a 79 year old male with numerous comorbidities including pulmonary fibrosis, who was found to have a biopsy proven peripheral and solitary non-small cell cancer. Due to prior SBRT (stereotactic body radiation therapy) with dose levels causing radiation fibrosis, he was not a candidate for repeat SBRT, and he was not a surgical candidate due to comorbidities. Tumor control with PDT was achieved without treatment related morbidity. This report details our findings.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

Genotypic and Phenotypic Variables Affect Meiotic Cell Cycle Progression, Tumor Ploidy, and Cancer-Associated Mortality in a brca2-Mutant Zebrafish Model.

Successful cell replication requires both cell cycle completion and accurate chromosomal segregation. The tumor suppressor BRCA2 is positioned to influence both of these outcomes, and thereby influence genomic integrity, during meiotic and mitotic cell cycles. Accordingly, mutations in BRCA2 induce chromosomal abnormalities and disrupt cell cycle progression in both germ cells and somatic cells. Despite these findings, aneuploidy is not more prevalent in BRCA2-associated versus non-BRCA2-associated human cancers. More puzzlingly, diploidy in BRCA2-associated cancers is a negative prognostic factor, unlike non-BRCA2-associated cancers and many other human cancers. We used a brca2-mutant/tp53-mutant cancer-prone zebrafish model to explore the impact of BRCA2 mutation on cell cycle progression, ploidy, and cancer-associated mortality by performing DNA content/cell cycle analysis on zebrafish germ cells, somatic cells, and cancer cells. First, we determined that combined brca2/tp53 mutations uniquely disrupt meiotic progression. Second, we determined that sex significantly influences ploidy outcome in zebrafish cancers. Third, we determined that brca2 mutation and female sex each significantly reduce survival time in cancer-bearing zebrafish. Finally, we provide evidence to support a link between BRCA2 mutation, tumor diploidy, and poor survival outcome. These outcomes underscore the utility of this model for studying BRCA2-associated genomic aberrations in normal and cancer cells.

Retention of cricothyrotomy skills by paramedics using a wire guided technique.

INTRODUCTION: Cricothyrotomy may be necessary for airway management when a patient's airway cannot be maintained through standard techniques such as oral airway placement, blind insertion airway device, or endotracheal intubation. Wire-guided cricothyrotomy is one of many techniques used to perform a cricothyrotomy. Although there is some controversy over which cricothyrotomy technique is superior, there is no published data regarding long term retention rates. The purpose of this study is to determine whether ground based paramedics can be taught and are able to retain the skills necessary to successfully perform a wire-guided cricothyrotomy. METHODS: This retrospective study was performed in a suburban county with a population of 160,000 with 23,000 EMS calls per year. Participants were ground-based paramedics who were taught wire-guided cricothyrotomy as part of a standardized paramedic educational update program. After viewing an instructional video, the paramedics were shown each the steps of the procedure on a simulation model, using a low fidelity task trainer previously developed to train emergency medicine residents. Using a 16 step procedural checklist, participants were allowed open-ended practice using the task trainer. Critical steps in the checklist were marked in bold lettering indicating automatic failure. Each paramedic was then individually supervised performing a minimum of 5 successful simulations. Retention was assessed using the same 16 step checklist 6 to 12 weeks following the initial training. RESULTS: A total of 55 paramedics completed both the initial training and reassessment during the time period studied. During the initial training phase 100% (55 of 55) of the paramedics were successful in performing all 16 steps of the wire-guided cricothyrotomy. During the retention phase, 87.3% (48 of 55) of paramedics retained the skills necessary to successfully perform the wire-guided cricothyrotomy. On the 16 step checklist, most steps were performed successfully by all the paramedics or missed by only 1 of the 55 paramedics. The step involving removal of the needle prior to advancing the airway device over the guide wire was missed by 34.5% (19 of 55) of the participants. This was not an automatic failure since most participants immediately self-corrected and completed the procedure successfully. CONCLUSION: Paramedics can be taught and can retain the skills necessary to successfully perform a wire-guided cricothyrotomy on a simulator. Future research is necessary to determine if paramedics can successfully transfer these skills to real patients.

Bronchoscopically Delivered Thermal Vapor Ablation of Human Lung Lesions.

BACKGROUND: The discovery that early diagnosis can reduce the mortality of lung cancer provides firm evidence that early surgical intervention is effective. However, surgical resection is available only to those who are healthy enough to tolerate the procedure. Vapor ablation may provide an additional method of treating the lung cancer patient, and has been studied in humans for emphysema treatment. In swine, we previously demonstrated that bronchoscopically delivered thermal vapor ablation (BTVA) could be accurately applied, was uniform, anatomically confined, and was tolerated by the animal. To provide evidence that BTVA may be a feasible method of treatment in humans, and since human and swine lungs have differing airway and segmental anatomy, we extended our studies to deceased human lungs to determine if anatomically confined and uniform ablations could be obtained with levels of energy comparable with our swine and human emphysema studies. METHODS: We obtained fresh, deceased human lungs and performed BTVA with increasing energy in subsegmental regions of lung containing tumors as well as non-tumor-containing areas in order to determine if uniform ablations with sharp boundaries could be obtained in human lung. RESULTS: We found that all ablations were anatomically contained. The frequency of uniform ablation effect was dependent on the total energy delivered and was achieved at a greater frequency than those with sharp boundaries. If a lung tumor was contained within the anatomy of the subsegment, the ablation zone completely surrounded the tumor. CONCLUSION: We conclude that BTVA may have a future role in the treatment of lung cancer and should be investigated further in clinical trials.

Effectiveness of Reprocessing for Flexible Bronchoscopes and Endobronchial Ultrasound Bronchoscopes.

BACKGROUND: Infections have been linked to inadequately reprocessed flexible bronchoscopes, and recent investigations determined that pathogen transmission occurred even when bronchoscope cleaning and disinfection practices aligned with current guidelines. This multisite, prospective study evaluated the effectiveness of real-world bronchoscope reprocessing methods, using a systematic approach. METHODS: This study involved direct observation of reprocessing methods for flexible bronchoscopes, multifaceted evaluations performed after manual cleaning and after high-level disinfection, and assessments of storage conditions. Visual inspections of ports and channels were performed using lighted magnification and borescopes. Contamination was detected using microbial cultures and tests for protein, hemoglobin, and adenosine triphosphate (ATP). Researchers assessed reprocessing practices, and storage cabinet cleanliness was evaluated by visual inspection and ATP tests. RESULTS: Researchers examined 24 clinically used bronchoscopes. After manual cleaning, 100% of bronchoscopes had residual contamination. Microbial growth was found in 14 fully reprocessed bronchoscopes (58%), including mold, Stenotrophomonas maltophilia, and Escherichia coli/Shigella species. Visible irregularities were observed in 100% of bronchoscopes, including retained fluid; brown, red, or oily residue; scratches; damaged insertion tubes and distal ends; and filamentous debris in channels. Reprocessing practices were substandard at two of three sites. CONCLUSIONS: Damaged and contaminated bronchoscopes were in use at all sites. Inadequate reprocessing practices may have contributed to bioburden found on bronchoscopes. However, even when guidelines were followed, high-level disinfection was not effective. A shift toward the use of sterilized bronchoscopes is recommended. In the meantime, quality management programs and updated reprocessing guidelines are needed.

The impact of ileal pouch-anal anastomosis on graft survival following liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes. AIM: To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA) vs retaining an end ileostomy on liver-related outcomes post-transplantation. METHODS: Graft survival was evaluated across a prospectively accrued transplant database, stratified according to colectomy status and type. RESULTS: Between 1990 and 2016, 240 individuals with PSC/colitis underwent transplantation (cumulative 1870 patient-years until first graft loss or last follow-up date), of whom 75 also required colectomy. A heightened incidence of graft loss was observed for the IPAA group vs those retaining an end ileostomy (2.8 vs 0.4 per 100 patient-years, log-rank P = 0.005), whereas rates between IPAA vs no colectomy groups were not significantly different (2.8 vs 1.7, P = 0.1). In addition, the ileostomy group experienced significantly lower graft loss rates vs. patients retaining an intact colon (P = 0.044). The risks conferred by IPAA persisted when taking into account timing of colectomy as related to liver transplantation via time-dependent Cox regression analysis. Hepatic artery thrombosis and biliary strictures were the principal aetiologies of graft loss overall. Incidence rates for both were not significantly different between IPAA and no colectomy groups (P = 0.092 and P = 0.358); however, end ileostomy appeared protective (P = 0.007 and 0.031, respectively). CONCLUSION: In PSC, liver transplantation, colectomy + IPAA is associated with similar incidence rates of hepatic artery thrombosis, recurrent biliary strictures and re-transplantation compared with no colectomy. Colectomy + end ileostomy confers more favourable graft outcomes.

It's all about the perspective: Removing bias when co-managing patients with high-grade T1 bladder cancer and localized prostate cancer-A competing risks analysis.

The risk connotation of terminology in influencing decision-making should not be underestimated. For example, "superficial" T1HG bladder cancer has the same poor cancer-specific survival as that conferred by the "highest risk" prostate cancer (Gleason 10, T3b). Co-management of concomitant prostate cancer and non-muscle invasive bladder cancer requires a careful competing risk analysis by both the physician and patient. Herein, we detail how patients and physicians should be careful not to underestimate the risk attributed to "non-muscle invasive" bladder cancer.

Membrane mechanics govern spatiotemporal heterogeneity of endocytic clathrin coat dynamics.

Dynamics of endocytic clathrin-coated structures can be remarkably divergent across different cell types, cells within the same culture, or even distinct surfaces of the same cell. The origin of this astounding heterogeneity remains to be elucidated. Here we show that cellular processes associated with changes in effective plasma membrane tension induce significant spatiotemporal alterations in endocytic clathrin coat dynamics. Spatiotemporal heterogeneity of clathrin coat dynamics is also observed during morphological changes taking place within developing multicellular organisms. These findings suggest that tension gradients can lead to patterning and differentiation of tissues through mechanoregulation of clathrin-mediated endocytosis.

Interrogating Bronchoalveolar Lavage Samples via Exclusion-Based Analyte Extraction.

Although average survival rates for lung cancer have improved, earlier and better diagnosis remains a priority. One promising approach to assisting earlier and safer diagnosis of lung lesions is bronchoalveolar lavage (BAL), which provides a sample of lung tissue as well as proteins and immune cells from the vicinity of the lesion, yet diagnostic sensitivity remains a challenge. Reproducible isolation of lung epithelia and multianalyte extraction have the potential to improve diagnostic sensitivity and provide new information for developing personalized therapeutic approaches. We present the use of a recently developed exclusion-based, solid-phase-extraction technique called SLIDE (Sliding Lid for Immobilized Droplet Extraction) to facilitate analysis of BAL samples. We developed a SLIDE protocol for lung epithelial cell extraction and biomarker staining of patient BALs, testing both EpCAM and Trop2 as capture antigens. We characterized captured cells using TTF1 and p40 as immunostaining biomarkers of adenocarcinoma and squamous cell carcinoma, respectively. We achieved up to 90% (EpCAM) and 84% (Trop2) extraction efficiency of representative tumor cell lines. We then used the platform to process two patient BAL samples in parallel within the same sample plate to demonstrate feasibility and observed that Trop2-based extraction potentially extracts more target cells than EpCAM-based extraction.

Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies.

OBJECTIVES: Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. MATERIALS AND METHODS: We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer's solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. RESULTS: The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). CONCLUSIONS: This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials.Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427-435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1.

Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite: a prospective series of 100 cases.

AIMS: Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects. PATIENTS AND METHODS: We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions. All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure. RESULTS: Patients were followed up for a mean of 19.5 months (12 to 34). Infection was eradicated in 96 patients with a single procedure and all four recurrences were successfully managed with repeat surgery. Adverse events were uncommon, with three fractures, six wound leaks and three unrelated deaths. Outcome was not dependant on C-M host class, microbial culture, wound leakage or presence of nonunion. CONCLUSION: This single-stage protocol, facilitated by the absorbable local antibiotic, is effective in the treatment of chronic osteomyelitis. It offers a more patient-friendly treatment compared with other published treatment options. Cite this article: Bone Joint J 2016;98-B:1289-96.