Adjusting diffusing capacity for anemia in patients undergoing allogeneic HCT: a comparison of two methodologies.

BACKGROUND: Diffusing capacity (DLCO) measurements are affected by hemoglobin. Two adjustment equations are used: Cotes (recommended by ATS/ERS) and Dinakara (used in the hematopoietic stem cell transplantation comorbidity index [HCT-CI]). It is unknown how these methods compare, and which is better from a prognostication standpoint. STUDY DESIGN: This is a retrospective cohort of 1273 adult patients who underwent allogeneic HCT, completed a pre-transplant DLCO and had a concurrent hemoglobin measurement. Non-relapse mortality was measured using competing risk analysis. RESULTS: Patients had normal spirometry (FEV1 99.7% [IQR: 89.4-109.8%; FVC 100.1% [IQR: 91.0-109.6%] predicted), left ventricular ejection fraction (57.2[6.7]%) and right ventricular systolic pressure (30.1[7.0] mmHg). Cotes-DLCO was 85.6% (IQR: 76.5-95.7%) and Dinakara-DLCO was 103.6% (IQR: 90.7-117.2%) predicted. For anemic patients (Hb<10g/dL), Cotes-DLCO was 84.2% (IQR: 73.9-94.1%) while Dinakara-DLCO 111.0% (97.3-124.7%) predicted. Cotes-DLCO increased HCT-CI score for 323 (25.4%) and decreased for 4 (0.3%) patients. Cotes-DLCO was superior for predicting non-relapse mortality: for both mild (66-80% predicted, HR 1.55 [95%CI: 1.26-1.92, p < 0.001]) and moderate (<65% predicted, HR 2.11 [95%CI: 1.55-2.87, p<0.001]) impairment. In contrast, for Dinakara-DLCO, only mild impairment (HR 1.69 [95%CI 1.26-2.27, p < 0.001]) was associated with lower survival while moderate impairment was not (HR 1.44 [95%CI: 0.64-3.21, p = 0.4]). In multivariable analyses, after adjusting for demographics, hematologic variables, cardiac function and FEV1, Cotes-DLCO was predictive of overall survival at 1-year (OR 0.98 [95%CI: 0.97-1.00], p = 0.01), but Dinakara-DLCO was not (OR 1.00 [95%CI: 0.98-1.00], p = 0.20). CONCLUSION: The ERS/ATS recommended Cotes method likely underestimates DLCO in patients with anemia, whereas the Dinakara (used in the HCT-CI score) overestimates DLCO. The Cotes method is superior to the Dinakara method score in predicting overall survival and relapse-free survival in patients undergoing allogeneic HCT.

Diagnostic Yield of 16S Ribosomal Ribonucleic Acid Gene-Based Targeted Metagenomic Sequencing for Evaluation of Pleural Space Infection: A Prospective Study.

Objective: To better understand the microbial profile of complicated parapneumonic effusions and empyema, and to evaluate whether antimicrobial selection would differ if guided by targeted metagenomic sequencing (tMGS) vs conventional cultures (CCs) alone. Patients and Methods: We analyzed the pleural fluid of a cohort of 47 patients undergoing thoracentesis from January 1, 2017 to August 31, 2019, to characterize their microbial profile. All samples underwent 16S ribosomal ribonucleic acid gene polymerase chain reaction, followed by tMGS. Results: Pleural space infection was deemed clinically present in 20 of the 47 (43%) participants. Of those, n=7 (35%) had positive pleural fluid cultures and n=14 (70%) had positive tMGS results. The organisms identified by tMGS were concordant with CCs; however, tMGS detected additional bacterial species over CCs alone. Streptococcus and Staphylococcus species were the most common organisms identified, with Streptococcus intermedius/constellatus identified in 5 patients. Polymicrobial infections were found in 6 of the 20 patients, with anaerobes being the most common organisms identified in these cases. Conclusion: Streptococci and staphylococci were the most common organisms identified in infected pleural fluid. Anaerobes were common in polymicrobial infections. When compared with CCs, tMGS had higher sensitivity than CCs. Targeted metagenomic sequencing identified additional organisms, not identified by CCs, with associated potential management implications.

Hypoxaemia in patients with heart failure and preserved ejection fraction.

AIMS: It is widely held that heart failure (HF) does not cause exertional hypoxaemia, based upon studies in HF with reduced ejection fraction, but this may not apply to patients with HF and preserved ejection fraction (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxaemia in HFpEF. METHODS AND RESULTS: Patients with HFpEF (n = 539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxaemia (oxyhaemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxaemia (n = 403), patients with hypoxaemia were older and more obese. Patients with HFpEF and hypoxaemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial oxygen difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxaemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and pulmonary capillary pressures were related to lower arterial oxygen tension (PaO2 ), especially during exercise. Body mass index (BMI) was not correlated with the arterial PaO2 , and hypoxaemia was associated with increased risk for death over 2.8 (interquartile range 0.7-5.5) years of follow-up, even after adjusting for age, sex, and BMI (hazard ratio 2.00, 95% confidence interval 1.01-3.96; p = 0.046). CONCLUSION: Between 10% and 25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxaemia is associated with more severe haemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.

A 64-year-Old patient assigned male at birth with COPD and worsening dyspnea while on estrogen and antiandrogen agents.

Among patients with COPD, ventilatory inefficiency in response to exercise can be due to respiratory muscle dysfunction or expiratory flow limitation causing air-trapping and dynamic hyperinflation. We discuss a case of severe ventilatory limitation in response to exercise due to reduced respiratory muscle mass in the setting of gender-affirming hormone therapy (GAHT), and how the interpretation of pulmonary function testing (PFT) and respiratory symptoms among transgender and gender diverse (TGD) patients can be influenced by GAHT.

Isolated Elevation in Lung Residual Volume Is Associated With Airway Diseases.

BACKGROUND: Residual volume (RV) is a derived lung compartment that correlates with air trapping in the context of air flow obstruction on spirometry. The significance of an isolated elevation in RV in the absence of other pulmonary function test (PFT) abnormalities is not well defined. We sought to assess the clinical and radiologic findings associated with isolated elevation in RV. METHODS: We searched our out-patient PFT database at Mayo Clinic (Rochester, Minnesota) from 2016-2018 for adult patients with isolated elevation in RV. We defined isolated elevation in RV as RV ≥ upper limit of normal or ≥ 130% predicted with normal total lung capacity (TLC), spirometry, and diffusion capacity of the lung for carbon monoxide (DLCO). We then matched this high-RV group by age and sex to an equal number of individuals with normal RV, TLC, spirometry, and DLCO (normal-RV group). RESULTS: We identified 169 subjects with isolated elevation in RV on PFTs, with a median age of 73 y; 55.6% were female, and median body mass index was 26.8 (vs 29.8 in the normal-RV group). The median RV was 3.08 L (134% predicted, interquartile range [IQR] 130-141) in the high-RV group and 2.26 L (99% predicted, IQR 90-109) in the normal-RV group (P < .001). Subjects with high RV were more likely to have smoked (54% vs 40%, P = .01) and almost twice as likely to have a maximum voluntary ventilation < 30 times the FEV1 (21% vs 12%, P = .02). Clinically, asthma (21% vs 11%, P = .01) and non-tuberculous mycobacterial lung infections (12% vs 2%, P = .001) were more prevalent in the high-RV group. On chest computed tomography, bronchiectasis (31% vs 15%, P = .008), bronchial thickening or mucus plugging (46% vs 22%, P < .001), and emphysema (13% vs 5%, P = .046) were more common in the high-RV group. CONCLUSIONS: Isolated elevation in RV on PFTs is a clinically relevant abnormality associated with airway-centered diseases.

Use of a Viral Filter to Reduce Exposure to Exhaled Aerosol Does Not Affect Methacholine Dose Delivery During Bronchoprovocation Testing.

BACKGROUND: Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyper-responsiveness. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb substantially reduced expelled particles during MCT. Our aim was to evaluate whether this modification affects the delivered dose of methacholine. METHODS: A mechanical ventilator was connected to a lung simulator with breathing frequency 15 breaths/min, tidal volume 500 mL, inspiratory-expiratory ratio 1:1, with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson Micro Mist or AeroEclipse II BAN nebulizers powered by either a dry gas source or a compressor system. A filter placed in line between the nebulizer and test lung was weighed before and after 1 min of nebulized methacholine delivery. Mean inhaled mass was measured with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles < 5 µm) and inhalation time. Unpaired t test was used to compare methacholine dose delivery with and without viral filter placement. RESULTS: The addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using a 50-psi dry gas source, dose delivered with or without a viral filter did not differ with the Hudson (422.3 µg vs 282.0 µg, P = .11) or the AeroEclipse nebulizer (563.0 µg vs 657.6 µg, P = .59). Using the compressor, dose delivered with and without a viral filter did not differ with the Hudson (974.0 µg vs 868.0 µg, P = .03) or the AeroEclipse nebulizer (818.0 µg vs 628.5 µg, P = .42). CONCLUSIONS: The addition of a viral filter to the nebulizer exhalation limb did not affect methacholine dose during bronchoprovocation testing. Routine use of a viral filter should be considered to improve pulmonary function technician safety and infection control measures during the ongoing COVID-19 pandemic.

Aerosol Generation and Mitigation During Methacholine Bronchoprovocation Testing: Infection Control Implications in the Era of COVID-19.

BACKGROUND: Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. METHODS: Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02-1 µm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. RESULTS: Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02-1 µm) concentrations decreased 77%-91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). CONCLUSIONS: The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.

Aerosol Generation During Peak Flow Testing: Clinical Implications for COVID-19.

BACKGROUND: Peak flow testing is a common procedure performed in ambulatory care. There are currently no data regarding aerosol generation during this procedure. Given the ongoing debate regarding the potential for aerosol transmission of SARS-CoV-2, we aimed to quantify and characterize aerosol generation during peak flow testing. METHODS: Five healthy volunteers performed peak flow maneuvers in a particle-free laboratory space. Two devices continuously sampled the ambient air during the procedure. One device can detect ultrafine particles 0.02-1 µm in diameter, while the second device can detect particles 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm in diameter. Five different peak flow meters were compared to ambient baseline during masked and unmasked tidal breathing. RESULTS: Ultrafine particles (0.02-1 µm) were generated during peak flow measurement. There was no significant difference in ultrafine particle mean concentration between peak flow meters (P = .23): Respironics (1.25 ± 0.47 particles/mL), Philips (3.06 ± 1.22), Clement Clarke (3.55 ± 1.22 particles/mL), Respironics Low Range (3.50 ± 1.52 particles/mL), and Monaghan (3.78 ± 1.31 particles/mL). Ultrafine particle mean concentration with peak flow testing was significantly higher than masked (0.22 ± 0.29 particles/mL) and unmasked tidal breathing (0.15 ± 0.18 particles/mL, P = .01), but the ultrafine particle concentrations were small compared to ambient particle concentrations in a pulmonary function testing room (89.9 ± 8.95 particles/mL). CONCLUSIONS: In this study, aerosol generation was present during peak flow testing, but concentrations were small compared to the background particle concentration in the ambient clinical environment. Surgical masks and eye protection are likely sufficient infection control measures during peak expiratory flow testing in asymptomatic patients with well controlled respiratory symptoms, but COVID-19 testing remains prudent in patients with acute respiratory symptoms prior to evaluation and peak expiratory flow assessment while the community prevalence of SARS-CoV-2 cases remains high.

Particulate generation with different oxygen delivery devices.

BACKGROUND: The Coronavirus pandemic has a high mortality rate in patients that are mechanically ventilated, which has led to an ever increasing interest in noninvasive forms of oxygenation. The use of these devices has the theoretical risk of increased exposure risk because of possible particulate generation. This study aimed to quantify the particulate generation associated with different oxygen devices. METHODS: This was a prospective single center study conducted during September 2020 using ten healthy adult volunteers. Testing was conducted in a negative pressure hospital room using a light scattering particle counter. The oxygen devices used were a nasal cannula, an OxyMask™, a non-rebreathing mask, and a high flow system. Particle measurements were obtained at baseline in the room and then with each oxygen delivery device and pre-specified oxygen flow rates. These measurements were obtained different distances from the volunteer with their mouth open. A Wilcoxon/Kruskal-Wallis test was performed on each separate oxygen modality with all flow rates as one model. RESULTS: The particle concentrations were slightly non-significantly increased with the OxyMask™ and non-rebreathing mask at the closest distance measured. As the distance increased, these counts decreased closer to ambient levels. The nasal cannula and high flow nasal cannula particle counts were not significantly different from ambient measurements at either distance. CONCLUSION: Nasal cannula, OxyMask™, non-rebreathing mask, and high flow oxygen did not generate any additional aerosols or droplets above a baseline room measurement, but further studies are necessary to determine infectious risk.

Characterizing Particulate Generation During Cardiopulmonary Rehabilitation Classes With Patients Wearing Procedural Masks.

BACKGROUND: The clinical benefits of cardiopulmonary rehabilitation are extensive, including improvements in health-related quality of life, emotional condition, physical function, and overall mortality. The COVID-19 pandemic continues to have a negative impact on center-based cardiopulmonary rehabilitation. Justifiable concern exists that the exercise-related increase in pulmonary ventilation within the rehabilitation classes may lead to the generation of infectious respiratory particles. RESEARCH QUESTION: Is cardiopulmonary rehabilitation while wearing a procedural mask a particle-generating procedure? STUDY DESIGN AND METHODS: Data were collected prospectively at a cardiopulmonary rehabilitation facility with all patients wearing a procedural mask. Small (0.3-4.9 µm) and large (5-10 µm) particle generation was quantified using a light-scattering particle counter. Data were analyzed by time, exertion level, and number of participants. RESULTS: A total of 24 distinct patients attended two or more of the cardiopulmonary rehabilitation classes tested. Most of the patients were men (n = 16 [67%]) and were in rehabilitation because of cardiac disease. During the cardiopulmonary rehabilitation class, small and large micrometer-size particles increased with increasing class size. In classes with four patients or more, a significant increase was found from ambient levels in both small (four patients, P < .01; and five patients, P < .01) and large (four patients, P < .01; and five patients, P < .01) particle count that peaked at about 35 to 40 min during each class. INTERPRETATION: Using an airborne particle counter, we found significant exercise-related increases in both small and large micrometer-size particle generation during cardiopulmonary rehabilitation classes, with larger class sizes (ie, more patients), despite participants wearing a procedural mask.

[Management of late onset septic complications after IPOM implantation: case series from a hernia center]. / Management septischer Spätkomplikationen nach IPOM-Implantation: Fallserie aus einem Hernienzentrum.

BACKGROUND: The intraperitoneal onlay mesh (IPOM) is for many surgeons a pragmatic solution for the operative treatment of extensive and complex abdominal wall hernias. A few years after mesh implantation we are now faced with a number of late complications of the IPOM procedure. Chronic septic complications, such as mesh infections and fistula formation have an outstanding position. OBJECTIVE: With this case series we would like to share our experiences with the operative treatment of severe late onset septic complications after abdominal wall augmentation with IPOM. Furthermore, the current indications for the IPOM procedure are discussed. MATERIAL AND METHODS: For the period February 2016-July 2019 a total of 10 patients with late septic complications after IPOM implantation were treated in our clinic. The index interventions took place between 2010 and 2017. The clinical picture varied from mesh infections with only minor symptoms to formation of multiple intestinal fistulas. RESULTS: Multiple stage procedures were required in 9 out of the 10 patients in order to achieve sufficient decontamination of the surgical field. Due to enterocutaneous fistulas, bowel resection was performed in 5 patients. The mesh could be preserved in situ in only one patient. For the reconstruction of the abdominal wall, both plastic surgical methods and implantation of absorbable and non-absorbable meshes were used. CONCLUSION: A consistent treatment with great effort is required for septic complications of the IPOM procedure. The interventions are often associated with extensive adhesiolysis and intestinal resection. Therefore, the indications for intraperitoneal mesh implantation should be handled with caution and an alternative surgical procedure should be considered. There are still special cases, such as hernias with very large abdominal wall defects in which the IPOM method is a suitable treatment option for tension-free reconstruction.

[Challenges in visceral medicine during COVID-19]. / Herausforderungen der Viszeralmedizin bei COVID-19: Erfahrungen aus einem Krankenhaus der Grund- und Regelversorgung.

BACKGROUND: The worldwide dissemination of the coronavirus disease 2019 (COVID-19) pandemic has become a relevant problem for the German healthcare system and the whole of society within only a few weeks. Because visceral medicine is at the focal point many adjustments in procedures are necessary. MATERIAL AND METHODS: Necessary organizational structures and challenges in visceral medicine are described for urgent abdominal surgery after screening and for patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, an analysis of the current and relevant literature was performed and changes in the procedures in a hospital for basic and standard healthcare in Lower Rhine are described. RESULTS: This article describes the organizational structures and changes in a German hospital facing the crisis and management during the pandemic. These include establishment of a corona screening center at the hospital's main entrance and a multidisciplinary crisis management team. Specific internal guidelines were formulated for the management, confirmed by international experience and studies and regularly changed due to the requirements of the situation. CONCLUSION: In comparison to other countries the crisis reached hospitals in Germany with a clear delay and a relatively mild course. In order to be prepared for severely ill patients, adequate preparations could be made to meet the challenges on intensive care units, isolation wards, operating theaters and in endoscopy. The primary goal was the safeguarding of patients and employees. In the light of the pandemic medical rituals and habits need to be reconsidered.

Visualization of skull remodeling and re-ossification after reconstructive surgery and mosaic-like cranioplasty in sagittal synostosis and deformational brachycephaly1.

INTRODUCTION: Extended vertex craniectomy in sagittal synostosis (SS) and transposition craniectomy in severe deformational brachycephaly (DB) combined with mosaic-like cranioplasty (M-LC) have been performed in 17 and 24 infants from 2001 to 2003. The hitherto not well-known mechanisms of remodeling and effectiveness of M-LC is assessed by X-ray and anthropometry. METHODS: Follow-ups included skull radiograms preoperatively and 3 and 15 months postoperatively, which were analyzed by craniometry according to Haas, long-term anthropometry, and clinical follow-up till mean age of 7.6 and 7.4 years. Analysis included the following: time course of cephalic indexes (CI), sizes of distances (breadth, length, height) and modulus, and mean deviation of distances and modulus from the normal age- and sex-dependent values; evaluation of re-ossification of the operative defects covered by M-L C. RESULTS: CI in SS is normalized in early follow-up with stabilization thereafter; CI of DB is gradually normalized till late follow-up. Remodeling occurs in both disorders by active and passive mechanisms: increased growth of distances with preoperative minus and decreased growth of distances with surplus. The latter mechanism adds more to the postoperative remodeling. M-LC leads to concentric and final complete re-ossification of the defects. DISCUSSION: Significant remodeling of the skull vault is observed in both disorders by the demonstrated time course and mechanisms. M-LC does not hinder early remodeling and guarantees re-ossification of the defects.

Solid Organ Transplantation After Retrieval From Deceased Donors With Abdominal Aortic Grafts.

INTRODUCTION: Organ procurement from deceased donors has been steadily augmented over the last 20 years. With a more aged donor population, a higher incidence of intraabdominal pathologies, including abdominal aortic aneurysms and atherosclerotic aortic disease, is commonly being encountered. The objective of our study was to report our institutional experience with abdominal aortic grafts during solid organ harvesting. PATIENTS AND METHODS: Data concerning the presence of aortic grafts in deceased solid organ donors during a 36-month period were retrospectively reviewed. RESULTS: During the study period, the organ retrieval team of our institution performed 246 multiorgan retrievals from deceased donors. More specifically, we harvested 6 livers and 12 kidneys from 6 donors with abdominal aortic grafts, which were not known/diagnosed to the organ retrieving team prior to the harvesting procedure. Severe atherosclerosis was present in all these donors. All 18 harvested organs were successfully transplanted. Apart of the absence of the aortic patch in 5 kidney grafts, no further special technical difficulties have been reported by the transplant teams. Data analysis of the recipient and graft outcome was performed through the Eurotransplant database. CONCLUSION: There are so far no literature data on the outcome of recipients and grafts from deceased donors with abdominal aortic grafts. Although retrieval of such organs is very challenging and requires a very experienced team, the transplantation of the corresponding organs can be performed without special technical problems.

Surgery for colorectal cancer in elderly patients: is there such a thing as being too old?

INTRODUCTION: The overall increase in life expectancy causes a rapid increase in number of elderly patients needing colorectal surgery. It remains unclear if there is a significant risk factor in patients over 80 years of age for postoperative morbidity and mortality. For this reason we investigated the perioperative, outcome and long-term survival after surgery for colorectal cancer in our hospital. MATERIALS AND METHODS: We retrospectively analysed a database containing information about patients who underwent surgery for colorectal cancer from January 2010 to December 2015 at the St. Bernhard Hospital in Kamp-Lintfort, Germany. The last follow-up date was 31th of December 2017. RESULTS: A total of 232 patients were enrolled and analysed in this study. All patients were separated in tow groups depending in age. The first group was ≥80 years old (n=49). The second group was <80 years old (n=183). High ASA-Scores (≥3) were detectable more often in elderly patients (p<0,05). Elderly and young patients had a similar risk for postoperative anastomosic leakages (p=0,047). Likewise there were no significant differences regarding the Dindo-Clavien-Classification (p=0,13). The mortality within the first 30 days after surgery was significant elevated for elderly patients compared to younger patients (p=0,04). Also the overall 1-year survival was 90% for the younger and 73,5% for the older study group (p<0,05) Conclusion. Both the short-term outcome and long-term survival rate after colorectal surgery for cancer are worse for patients older than 80 years of age. After interpretation of all data it remains unclear if the age itself is still the biggest risk factor. When old patients have a good ASA-Score and no severe comorbidities, colorectal surgery remains safe even for patients older than 80 years.