Pulmonary Side Research Articles

Analysis of Pulmonary Complications in Pediatric Acute Lymphocytic Leukemia Patients following Three Years of Chemotherapy Treatment: A Cross-Sectional Study

Background: This study aimed to investigate the pulmonary side effects of chemotherapy drugs in children with Acute Lymphocytic Leukemia (ALL) three years after treatment. The results could be of great help in managing lung complications in pediatric oncology patients. Materials and Methods: This cross-sectional descriptive study included 50 patients (22 males and 28 females) with ALL. Data were collected from patients' files, including age, sex, duration of illness, last dose of chemotherapy, and medications such as PEG.Asparginas, Cyclophosphamid, thioguanine, Dexamethason, cytarabin, cytosin.arabinosid, vincristine, mercaptopurine, and methotrexate. Pulmonary function tests (Forced Vital Capacity (FVC), FEV1 (Forced Expiratory Volume in the first second)) were assessed by spirometry. Results: Out of 50 patients, 47 (94%) did not have pulmonary disorders, while 3 (6%) had pulmonary dysfunction. Forty-seven patients (94%) did not have respiratory symptoms. FVC results showed that 45 patients were normal, and 5 were abnormal. Similarly, 45 patients had normal FEV1, and 5 had abnormal results. Spirometry results were normal in 45 patients and abnormal in 5. A significant relationship was found between the use of these drugs in different doses and spirometry results, recurrence rate, and pulmonary complications (P <0.05). No significant relationship was observed between pulmonary dysfunction and other drugs (P> 0.05). No correlation was found between pulmonary complications due to chemotherapy with duration of chemotherapy, patient age, and patient gender (P> 0.05). Conclusion: Pulmonary dysfunction and respiratory syndrome were observed in 6% of patients receiving chemotherapy. A significant relationship was found between the frequency of pulmonary and respiratory complications with some chemotherapy drugs in children with ALL. Further research is needed to optimize treatment strategies and minimize lung complications in pediatric oncology patients.

Evaluation of busulfan, cyclophosphamide, and etoposide as a preparation regimen for autologous stem cell transplantation in Hodgkin’s lymphoma patients

Abstract: BACKGROUND: Hodgkin’s lymphoma (HL) exhibits a cure rate of 90% in patients diagnosed at an early stage and a cure rate ranging from 70% to 90% in patients diagnosed at an advanced stage. In the case of patients with relapsed/refractory HL (r/rHL), it is recommended to provide salvage chemotherapy initially, followed by autologous stem cell transplantation (ASCT). The ideal conditioning regimen for the transplantation process is still being investigated. OBJECTIVES: For individuals with r/rHL, high-dose chemotherapy combined with ASCT (HD-ASCT) is thought to be the most effective method of treatment. The purpose of this research was to evaluate the effectiveness and safety of the busulfan, cyclophosphamide, and etoposide (BuCyE) preparation regimen in r/rHL patients. MATERIALS AND METHODS: Retrospective analysis was conducted on the data of 67 lymphoma patients older than 18 years who had HD-ASCT with the BuCyE conditioning regimen between September 2014 and November 2021 (86 months). The research consisted of 34 r/r HL patients among them. A parenteral regimen of 0.8 mg/kg of busulfan every 6 h from day −7 to day −5, 50 mg/kg of cyclophosphamide on days −3 and −2, and 400 mg/m2 of etoposide on days −5 and −4 comprised the patient preparation regimen before ASCT. All data were collected from inpatient files and the Inonu University Turgut Ozal Medical Center Hospital Information System. RESULTS: The median age of the patients was 43 years, and 67.6% were males. The most common type of HL was nodular sclerosis, which was followed by mixed cellularity. The median time for platelet and neutrophil engraftment was 14 and 11 days, respectively. 5.0 × 106/kg was the median transplanted dose of CD34+ cells (2.1–13.55). Liver toxicity was observed in 6 (17.6%) patients. Eight patients suffered from pulmonary side effects. The median number of previous chemotherapies was 2 (2–4). In all lymphoma patients, the complete response rate was 61.8% (n = 21), whereas the disease progression rate was 32.3% (n = 11). Transplantation-related mortality on the 100th day was 8.8% (n = 3). Three-year overall survival was 57.17%. CONCLUSION: When the literature was reviewed, the studies with the BuCyE preparation regimen in patients with r/rHL were limited. This conditioning regimen was found to have fewer side effects and a lower cost. It can be preferable when compared to carmustine (BCNU), etoposide, cytarabine (ARA-C), and melphalan (known as BEAM) in r/rHL.

Intranasal administration of sertraline ensures sustained brain delivery and antidepressant effect in a mouse model of depression

The pursuit of more potent and efficacious antidepressant therapies is of utmost significance. Herein, the intranasal (IN) route was investigated for sertraline brain delivery, encompassing a comparative pharmacokinetic study after a single-dose administration to mice by IN, intravenous (IV) (4.87 mg/kg) and oral (10 mg/kg) routes, and an efficacy/toxicity study to explore the therapeutic effect in mice subjected to the unpredictable chronic mild stress (UCMS) protocol. Neurotransmitters and melatonin were quantified in prefrontal cortex and plasma, respectively. A different drug biodistribution behavior was unveiled for a CNS-acting drug administered by means of the IN route. For the first time, IN administration of sertraline exhibited heightened systemic exposure (bioavailability = 166 %), and a sustained drug release into the brain, in opposition to IV and oral routes, avoiding drug fluctuation. The lower lung exposition (given by normalized area under the curve) observed after IN instillation envisions the reduction of sertraline pulmonary side effects and similarly other peripheral side effects. IN sertraline treatment displayed significant efficacy in ameliorating anhedonia after one week of administration while the 14-day IN treatment regimen translated into decreased immobility time and increased swimming time in the forced swimming test, suggesting an improvement of the depressive-like behavior displayed by the animal depressive-model. Remarkably, these effects were absent with oral sertraline, despite the higher used dose. Noteworthy neurotransmitter alterations were observed, with IN sertraline markedly reducing adrenaline in the prefrontal cortex, while serotonin and melatonin increased following both administration routes. With its sustained brain delivery and serotonin- and melatonin-enhancing potential, the innovative strategy of IN sertraline holds the potential not only to effectively address depressive symptoms but also to mitigate challenges inherent to classic treatments.

Using cryopreserved allogeneic pericardium to repair congenital heart defects in children

Patches prepared from autologous, allogeneic, or xenogeneic tissues are widely used in the repair of congenital heart defects in children. Since 2002, cryopreserved allogeneic pericardial patches have been prepared in our institution as an alternative to commercially available patches. This study retrospectively reviewed donor and patient data concerning cryopreservation time and the clinical use of the pericardium in 382 children who were operated on at a single center between 2004 and 2021. There were 177 donors: 98 males and 79 females. The median donor age was 13 years (range: 1 month to 53 years) and the median cryopreservation time was 72 days (range: 3–685). There were 382 pediatric patients: 224 males and 158 females. The median patient age was 1 month (range: 3 days to 17.8 years). The patches were used for primary surgeries in 228 patients and for reoperations in 154. The patches were implanted into the right heart or venous circulation in 209 patients, the left heart or arterial circulation in 246 patients, and both sides of the circulatory system in 73. Extracardiac patch implantation was performed in 339 patients, intracardiac in 79 patients, and both intracardiac and extracardiac in 36 patients. Our study presents a single-center experience in the use of cryopreserved allogeneic pericardium. The pericardium can be used on the systemic and pulmonary sides of the circulatory system, in either extracardiac or intracardiac positions. However, there is no uniform strategy for selecting the “patch of choice” for correcting congenital heart defects in children, especially since there are few studies comparing several types of patches.

Evaluation of pulmonary side effects in prolactinoma patients treated with cabergoline.

Cabergoline (CAB) is the most used dopamine agonist in the treatment of prolactinomas. Studies related to the treatment of Parkinson's disease have shown that dopamine agonists can lead to fibrotic syndromes affecting the heart and the lung. The aim of this study was to evaluate the possible pulmonary side effects of CAB in prolactinoma patients. Chest X-ray imaging and pulmonary function parameters like forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity for carbon monoxide (DLCO) were evaluated in 73 prolactinoma patients. The cumulative dose of CAB and the total duration of CAB use were also calculated, and all data were reviewed retrospectively. The median cumulative CAB dose was 192 mg, and the median duration of CAB use was 64 months. Only 13 patients (17%) among this cohort had abnormal DLCO results that could be an indirect sign of pulmonary fibrosis. These abnormal DLCO results were found not to be associated with cumulative CAB dose in these 13 patients. CAB appears to be safe in terms of pulmonary functions with a median cumulative dose of 192 mg in prolactinoma patients.

Antitumor Effect of Bleomycin Nanoaerosol in Murine Carcinoma Model.

Bleomycin, which is widely used as an antitumor agent, possesses serious adverse effects such as pulmonary toxicity. Local nanoaerosol deposition for lung cancer treatment is a promising alternative to drug delivery to lung lesions. The aim of this work is to test the hypothesis that bleomycin nanoaerosol can be effectively used to treat multiple lung metastases. To obtain bleomycin nanoaerosol, an aerosol generator based on electrospray of a solution of a nonvolatile substance with gas-phase neutralization of charged aerosol particles was used. Lung metastases in murine Lewis lung carcinoma and B16 melanoma animal models were counted. The effect of inhaled bleomycin nanoparticles on the number and volume of metastases, as well as pulmonary side effects, was investigated. Using a mouse exposure chamber, the dose-dependent effect of inhaled bleomycin on tumor volume was evaluated in comparison with intraperitoneal administration. Bleomycin nanoaerosol reduced the volume of metastases and produced a higher antitumor effect at much lower doses. It has been established that long-term exposure to nanoaerosol with a low dose of bleomycin is capable of suppressing cancer cell growth. The treatment was well tolerated. In the lungs, minor changes were found in the form of focal-diffuse infiltration of the lung parenchyma.

Acute and Chronic Pulmonary Side Effects of Drugs in Humans

Complications caused by the inhalation of microbial agents or their products, as well as inhaled toxic particles present in the space air of the surrounding environment lead to acute or chronic inflammation in the lung and other deep respiratory tissues. This can be the source of metastatic spread of inflammation in other organs. It becomes more dangerous, especially when these agents can disrupt the common regulatory defense system in the lungs. In the state of balance and health of the environment and avoiding exposure to hazardous inhalation agents, the respiratory system has the power to regulate inflammation.

The Impact of FEV1/FVC Ratio on the Clinical Outcomes in Acute Coronary Syndrome Patients Treated with Dual Anti-Platelet Agents.

Few studies have investigated the clinical efficacy and pulmonary side effects of different P2Y12 inhibitors in acute coronary syndrome (ACS) patients. The aim of this study was to explore the impact of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) ratio on the clinical outcomes in ACS patients treated with dual antiplatelet therapy after percutaneous coronary intervention (PCI). ACS patients who underwent PCI, had documented pre-existing spirometry tests, and received aspirin with either ticagrelor or clopidogrel were enrolled for retrospective analysis. Of the enrolled ACS patients, 275 and 247 received ticagrelor and clopidogrel, respectively. The incidence of wheeze was significantly higher in the ticagrelor group compared to the clopidogrel group within 360 days (14.91% vs. 8.09%, p = 0.016). Multivariable analysis revealed that ticagrelor treatment, as compared to clopidogrel treatment, independently predicted 1-year hospitalization for acute exacerbation (AE) of obstructive airway disease (hazard ratio: 3.44; 95% confidence interval: 1.92 to 6.15; p < 0.01). The receiver operating characteristic curve indicated that an FEV1/FVC ratio of 63.85% had the highest sensitivity and specificity for predicting the incidence of AE of obstructive airway disease within 1 year (p < 0.001). The 1-year hospitalization rate for AE of obstructive airway disease was significantly higher in the ticagrelor group when the FEV1/FVC ratio was < 63%. This study demonstrated higher incidence of wheeze and hospitalization for AE of obstructive airway disease in ACS patients treated with ticagrelor compared to clopidogrel. Furthermore, the FEV1/FVC ratio ≤ 63% in the ACS patients predicted hospitalization for AE of obstructive airway disease in 1 year.

The importance of lung recruitability: A novel ultrasound pattern to guide lung recruitment in neonates.

Lung Ultrasound (LUS)-guided Lung Recruitment Maneuver (LRM) has been shown to possibly reduce ventilator-induced lung injury in preterm infants. However, to avoid potential hemodynamic and pulmonary side effects, the indication to perform the maneuver needs to be supported by early signs of lung recruitability. Recently, a new LUS pattern (S-pattern), obtained during the reopening of collapsed parenchyma, has been described. This study aims to evaluate if this novel LUS pattern is associated with a higher clinical impact of the LUS-guided LRMs. All the LUS-guided rescue LRMs performed on infants with oxygen saturation/fraction of inspired oxygen (S/F) ratio below 200, were included in this cohort study. The primary outcome was to determine if the presence of the S-pattern is associated with the success of LUS-guided recruitment, in terms of the difference between the final and initial S/F ratio (Delta S/F). We reported twenty-two LUS-guided recruitments, performed in nine patients with a median gestational age of 34 weeks, interquartile range (IQR) 28-35 weeks. The S-pattern could be obtained in 14 recruitments (64%) and appeared early during the procedure, after a median of 2 cmH2O (IQR 1-3) pressure increase. The presence of the S-pattern was significantly associated with the effectiveness of the maneuver as opposed to the cases in which the S-pattern could not be obtained (Delta S/F 110 +/- 47 vs 44 +/- 39, p = 0.01). Our results suggest that the presence of the S-pattern may be an early sign of lung recruitability, predicting LUS-guided recruitment appropriateness and efficacy.

Moderne definitive Radiochemotherapie – State of the Art-Umsetzung und neue Konsolidierungsstrategien

BackgroundIn locally advanced non-small-cell lung cancer (NSCLC), the addition of chemotherapy to radiotherapy and consolidation with durvalumab leads to a significant increase in overall survival and represents the most profound innovation of the last decade.ObjectivesAnalysis of new possibilities for the state-of-the-art implementation of definitive radiochemotherapy concepts.Materials and methodsEvaluation of prospective and randomised studies regarding improvements in treatment outcomes.ResultsOverall survival benefit of consolidating checkpoint inhibitor therapy after combined radiochemotherapy with durvalumab is 43% (95% confidence interval 38–47%) versus 33% (27–40%) in the placebo group in an updated analysis of the PACIFIC trial for 5‑year survival; stratified hazard ratio for death is 0.72 (95% CI 0.59–0.89, p = 0.0025). In the dose escalation studies, increased pulmonary and oesophageal side effects were observed, so no immediate clinical benefit could be derived from the increase in local efficacy. Improved imaging before and during therapy and optimised possibilities of dose application, especially by using intensity-modulated radiotherapy (IMRT), allow selective sparing of healthy structures, which increases the ability to safely intensify radiotherapy also in connection with new immunomodulatory substance combinations.ConclusionThe integration of immunotherapy, the stringent use of fluorodeoxyglucose positron emission tomography (FDG-PET) in staging and radiation planning, the widespread use of highly conformal radiation techniques (IMRT; volumetric modulated arc therapy, VMAT) and the consistent application of image-guided radiotherapy have led to significant improvements in treatment outcomes.

Nicorandil mitigates amiodarone-induced pulmonary toxicity and fibrosis in association with the inhibition of lung TGF-β1/PI3K/Akt1-p/mTOR axis in rats.

The long-term side effect of the antiarrhythmic drug, amiodarone (AMIO), such as lung toxicity, remains a critical clinical issue. The previous knowledge denotes diverse antioxidant, anti-inflammatory, and antifibrotic properties of the anti-anginal drug, nicorandil (NI). Therefore, we aimed to investigate the possible protective effect of NI on pulmonary tissue remodelling following AMIO-induced lung toxicity. The included rats were assigned into four equal groups (n=8): (1) control, (2) control group that received NI 10mg kg-1 day-1 , (3) model group that received AMIO in a dose of 60 mg kg-1 day-1 , and (4) treated group (AMIO-NI) that were treated with AMIO plus NI as shown above. Drug administration continued for 10 weeks. AMIO resulted in deteriorated (p < 0.001) pulmonary functions accompanied by respiratory acidosis. AMIO showed an obvious histological injury score with intense collagen deposition, disturbed nitric oxide synthase enzymes (NOS/iNOS), and increased alpha smooth muscle actin expression. Furthermore, AMIO upregulated the transforming growth factor (TGF-β1)/phosphoinositide-3 kinase (PI3K)-Akt1-p/mammalian target of rapamycin (mTOR) axis, which determined the possible mechanism of AMIO on pulmonary remodelling. NI treatment significantly (p < 0.001) prevented the AMIO-induced lung toxicity, as well as inhibited the TGF-β1/PI3K/Akt1-p/mTOR axis in the lung tissue of rats. The results were confirmed by an in-vitro study. CONCLUSION: The current results revealed that NI was effective in preserving the lung structure and functions. Amelioration of the oxidative stress and modulation of TGF-β1/PI3K/Akt1-p/mTOR have been achieved. This study suggests NI administration as a preventive therapy from the serious pulmonary fibrosis side effect of AMIO.

Comparison of Aerosol Delivery Methods in Mechanically Ventilated Patients: Evaluating Differences in Drug Deposition, Patient Outcomes, and Side Effects

Background: Aerosol delivery methods vary in effectiveness and patient tolerance, particularly in mechanically ventilated patients. This study aims to compare Metered-Dose Inhalers (MDIs) with spacers, nebulizers, and Dry Powder Inhalers (DPIs) in terms of drug deposition, pulmonary function improvement, patient outcomes, and side effects. Methods: A mixed-methods approach was used, combining quantitative analysis of drug deposition, pulmonary function tests (PFTs), patient outcome scores, and side effect reporting with qualitative interviews from patients and clinicians. Data were collected from a sample of 120 mechanically ventilated patients across three hospitals. Results: Nebulizers demonstrated the highest mean drug deposition (45.8%) and pulmonary function improvement (22.3% change in FEV1), followed by MDIs with spacers (30.2% deposition, 15.5% improvement) and DPIs (25.0% deposition, 12.4% improvement). Nebulizers also had the highest patient outcome score (8.1), though with a higher incidence of side effects (22%). MDIs and DPIs had lower side effect rates (18% and 10%, respectively) and were preferred for their ease of use and quicker treatment times, despite lower efficacy. Conclusion: Nebulizers are more effective in delivering medication and improving pulmonary function but are associated with higher side effects. MDIs and DPIs, while less effective, offer benefits in terms of side effect profiles and patient convenience. Clinicians should weigh these factors when choosing aerosol delivery methods for mechanically ventilated patients.

Transcatheter closure of inferior sinus venosus defect using a patent ductus arteriosus occluder following simulation with a 3D-printed model.

BackgroundTranscatheter closure of inferior sinus venosus defect (ISVD) is still contraindication. To explore whether transcatheter closure with patent ductus arteriosus (PDA) occluders is possible for ISVD.MethodsFrom June 2014 to March 2021, 12 patients were recruited diagnosed as <25 mm ISVD. The three-dimensional printing (3DP) heart model was produced based on multi-slice computed tomography (MSCT) scans. Preoperative closure simulation was planned on the personalized 3D model for each patient. Follow-up including electrocardiography (ECG), transthoracic echocardiography (TTE), and X-ray was traced.Results3DP models of 12 patients were successfully printed. Twelve patients had been diagnosed with <25 mm ISVD and 4 of them had another secundum atrial septal defect (ASD). All patients were produced interventional therapy successfully. PDA occluder was implanted to closed ISVD, and ASD was closed using ASD occluder simultaneously. The average diameter of ISVD measured by TTE was (12.67±3.80), and the average diameter of sagittal axes and longitudinal axes measured by the 3D-printed model was (17.08±3.20) and (18.42±4.62) mm, respectively. The average size of PDA (diameter of pulmonary artery side) was (28.17±3.35) mm. Compared with the preoperative, the X-ray cardiothoracic ratio (0.51±0.04 vs. 0.47±0.06, P=0.007) and the right ventricle anterior-posterior diameter (31.17±5.65 vs. 24.58±3.75 mm, P<0.001) of postoperative was significantly decreased. During the average (47.75±27.52) months follow-up, it has achieved satisfying results, and there were no severe adverse events such as device transposition, death, and pericardial tamponade occurred.ConclusionsAssisting by 3D heart model, transcatheter closure of ISVD with PDA occluder had an excellent outcome. This method provides a new considerable treatment strategy for ISVD.

Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Trospective Comparison Focusing on Pulmonary Toxicity.

Simple SummaryThe standard of care (SoC) for patients with unresectable stage III non-small-cell lung cancer is concurrent chemoradiation followed by durvalumab. Because of co-morbidities, however, the concurrent approach is only amenable for about one-third of patients. While sequential regimens are usually regarded as palliative, these schedules applied in a dose-escalated mode may be part of a curative approach. As the combination of high-dose radiation and durvalumab remains a question of ongoing research, this retrospective study aims at evaluating pulmonary side effects after sequential chemoradiotherapy with high-dose irradiation compared to SoC. Radiation dose escalation showed no excess pulmonary toxicity such as pneumonitis but tendentially better intrathoracic control, suggesting that this alternative approach is safe and feasible.Introduction: The standard of care (SoC) for unresectable stage III non-small-cell lung cancer (NSCLC) is durvalumab maintenance therapy after concurrent chemoradiation in patients with PD-L1 > 1%. However, the concurrent approach is only amenable for about one-third of patients due to co-morbidities. Although sequential regimens are usually not regarded as curative, these schedules applied in a dose-escalated manner may be similarly radical as SoC. As combining high-dose radiation and durvalumab remains a question of debate this retrospective bi-center study aims to evaluate pulmonary toxicity after high-dose chemoradiotherapy beyond 70 Gy compared to SoC. Patients and Methods: Patients with NSCLC stage III received durvalumab after either sequential high-dose chemoradiation or concomitant SoC. Chemotherapy consisted of platinum combined with either pemetrexed, taxotere, vinorelbine, or gemcitabine. The primary endpoint was short-term pulmonary toxicity occurring within six months after the end of radiotherapy (RT). Results: A total of 78 patients were eligible for this analysis. 18F-FDG-PET-CT, cranial MRT, and histological/cytological verification were mandatory in the diagnostic work-up. The high-dose and SoC group included 42/78 (53.8%) and 36/78 (46.2%) patients, respectively, which were matched according to baseline clinical variables. While the interval between the end of RT and the start of durvalumab was equal in both groups (p = 0.841), more courses were administered in the high-dose cohort (p = 0.031). Pulmonary toxicity was similar in both groups (p = 0.599), whereas intrathoracic disease control was better in the high-dose group (local control p = 0.081, regional control p = 0.184). Conclusion: The data of this hypothesis-generating study suggest that sequential high-dose chemoradiation followed by durvalumab might be similar to SoC in terms of pulmonary toxicity and potentially more effective with respect to intra-thoracic disease control. Larger trials with a prospective design are warranted to validate these results.

Distribution of atrial low voltage induced by vein of Marshall ethanol infusion.

Systematic and quantitative descriptions of vein of Marshall (VOM)-induced tissue ablation are lacking. We sought to characterize the distribution of low voltage observed in the left atrium (LA) after VOM ethanol infusion. The distribution of ethanol-induced low voltage was evaluated by comparing high-density maps performed before and after VOM ethanol infusion in 114 patients referred for atrial fibrillation ablation. The two most frequently impacted segments were the inferior portion of the ridge (82.5%) and the first half of the mitral isthmus (pulmonary vein side) (92.1%). Low-voltage absence in these typical areas resulted from inadvertent ethanol infusion in the left atrial appendage vein (n = 3), initial VOM dissection (n = 3), or a "no branches" VOM morphology (n = 1). Visible anastomosis of the VOM with roof or posterior veins more frequently resulted in low-voltage extension beyond typical areas, toward the entire left antrum (19.0% vs. 1.9%, p = .0045) or the posterior LA (39.7% vs. 3.8%, p < .001) but with a limited positive predictive value ranging from 29.4% to 43.5%. Ethanol-induced low voltage covered a median LA surface of 3.6% (1.9%-5.0%) and did not exceed 8% of the LA surface in 90% of patients. VOM ethanol infusion typically locates at the inferior ridge and the adjacent half of the mitral isthmus. Low-voltage extensions can be anticipated but not guaranteed by the presence of visible anastomosis of the VOM with roof or posterior veins.

Electroconvulsive Treatment in Dementia With Lewy Bodies: A Case Report

We report the case of a 78-year-old female patient with dementia with Lewy bodies accompanying severe psychotic and parkinsonian symptoms. The patient s symptoms did not improved with various antipsychotics, and cardiac and pulmonary side effects prevented adequate doses of the drugs from being administered. As an alternative approach, we performed electroconvulsive therapy, which can be conducted relatively safely in elderly patients with underlying medical conditions. The patient received 10 sessions of electroconvulsive therapy across a 4-week period. Remarkable improvements in psychotic and parkinsonian symptoms proven with validated scales were observed following the repeating electroconvulsive therapy sessions. This is the first case report describing the use of electroconvulsive therapy in a patient with dementia with Lewy bodies in Korea. This case report may help to establish new guidelines for the treatment of patients with dementia with Lewy bodies, which is still considered a difficult disease to treat.

Therapeutic schemes of denosumab in the treatment of giant cell tumor of bone - Protocol for a systematic review with meta-analysis

The aim of this study is to evaluate the efficacy of different therapeutic regimens using denosumab in patients with giant cell tumor of bone (GCTB), regarding primary outcomes related to therapeutic response (lesion size, pain and function) and presentation to imaging exams, in addition to secondary outcomes related to age (in years) and tumor location, reduction or downgrade of surgical indication, local recurrence, presence of pulmonary metastases and therapeutic side effects. A systematic literature search will be carried out in the PubMed/MEDLINE, Embase (CAPES Journals), Science Direct/Elsevier, Scielo, Cochrane Library and clinical trial records (ClinicalTrials.gov and Registro Brasileiro de Ensaios Clínicos) databases; for exploration of grey literature, the Open Access Theses and Dissertations and the Biblioteca Digital Brasileira de Teses e Dissertações databases will be consulted. We will also conduct a "snowball" survey to identify additional eligible studies for full-text review. Two evaluators will select, extract and assess the risk of bias of the obtained data. If appropriate, a meta-analysis will be carried out, extracting data for the number of events and total patients to perform proportion meta-analysis using the R software, with the "meta" package (version 4.9–6), the "metaprop function" for aspect ratio data. The results of this review will provide convincing information on the efficacy of different therapeutic regimens using denosumab in GCTB, providing a reliable theoretical basis for the research that will follow.

Right-sided heart reperfusion ("Berlin bridge technique") for right ventricle support during left ventricular assist device (LVAD) implantation.

Right-sided heart reperfusion ("Berlin bridge technique") for right ventricle support during left ventricular assist device (LVAD) implantation.

An overview of the preclinical discovery and development of trastuzumab deruxtecan: a novel gastric cancer therapeutic

ABSTRACT Introduction Gastric cancer is common worldwide, and while multiple therapeutic options exist, the prognosis remains poor. Tumors may overexpress HER2. While targeting HER2 with trastuzumab provides a survival benefit, options following progression are limited. Subsequent trials of HER2-targeted agents failed to improve outcomes. Recently, DESTINY-Gastric01 demonstrated a survival benefit utilizing the antibody-drug conjugate (ADC) trastuzumab deruxtecan in gastric cancer patients that progressed on trastuzumab. Areas Covered /The authors give background to gastric cancer/HER2 and discuss prognostic implications of HER2 overexpression. They also describe initial trials of anti-HER2 therapy, resistance mechanisms, and ADC development/optimization. Finally, the authors review DESTINY-Gastric01 and provide future perspectives. Expert opinion While the 2010 ToGA trial demonstrated efficacy of trastuzumab in HER2 positive gastric cancer, subsequent trials of HER2-directed therapy have disappointed. Downregulation of HER2 after trastuzumab may play a role; however, trastuzumab deruxtecan maintains some efficacy in low-level HER2 expressing tumors. The DESTINY-Gastric01 cohort was from South Korea/Japan; authors have reported differences in gastric cancer risk factors/physiology between Eastern and Western populations. DESTINY-Gastric02 will evaluate trastuzumab deruxtecan in Western patients to confirm generalizability. Pulmonary side effects are notable;physicians must be cognizant of overlapping toxicities with combination therapy.

Fundamentals of vaping-associated pulmonary injury leading to severe respiratory distress.

Vaping of flavored liquids has been touted as safe alternative to traditional cigarette smoking with decreased health risks. The popularity of vaping has dramatically increased over the last decade, particularly among teenagers who incorporate vaping into their daily life as a social activity. Despite widespread and increasing adoption of vaping among young adults, there is little information on long-term consequences of vaping and potential health risks. This study demonstrates vaping-induced pulmonary injury using commercial JUUL pens with flavored vape juice using an inhalation exposure murine model. Profound pathological changes to upper airway, lung tissue architecture, and cellular structure are evident within 9 wk of exposure. Marked histologic changes include increased parenchyma tissue density, cellular infiltrates proximal to airway passages, alveolar rarefaction, increased collagen deposition, and bronchial thickening with elastin fiber disruption. Transcriptional reprogramming includes significant changes to gene families coding for xenobiotic response, glycerolipid metabolic processes, and oxidative stress. Cardiac systemic output is moderately but significantly impaired with pulmonary side ventricular chamber enlargement. This vaping-induced pulmonary injury model demonstrates mechanistic underpinnings of vaping-related pathologic injury.