Exercise Attenuate Diaphragm Atrophy in COPD Mice via Inhibiting the RhoA/ROCK Signaling.

Background: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear. Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1ß, TNF-α, and RhoA/ROCK were determined by Western blotting. Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably. Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.

Suppression of Ventilation-Induced Diaphragm Fibrosis through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K-γ pathway. Five days after receiving a single bolus of 0.075 units of bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg of MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-ß1, oxidative loads, Masson's trichrome staining, extracellular collagen levels, positive staining of α-smooth muscle actin, PI3K-γ expression, and myonuclear apoptosis (p < 0.05). Decreased diaphragm contractility and peroxisome proliferator-activated receptor-γ coactivator-1α levels were also observed (p < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K-γ activity (p < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated by PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Modulation of Titin and Contraction-Regulating Proteins in a Rat Model of Heart Failure with Preserved Ejection Fraction: Limb vs. Diaphragmatic Muscle.

Heart failure with preserved ejection fraction (HFpEF) is characterized by biomechanically dysfunctional cardiomyocytes. Underlying cellular changes include perturbed myocardial titin expression and titin hypophosphorylation leading to titin filament stiffening. Beside these well-studied alterations at the cardiomyocyte level, exercise intolerance is another hallmark of HFpEF caused by molecular alterations in skeletal muscle (SKM). Currently, there is a lack of data regarding titin modulation in the SKM of HFpEF. Therefore, the aim of the present study was to analyze molecular alterations in limb SKM (tibialis anterior (TA)) and in the diaphragm (Dia), as a more central SKM, with a focus on titin, titin phosphorylation, and contraction-regulating proteins. This study was performed with muscle tissue, obtained from 32-week old female ZSF-1 rats, an established a HFpEF rat model. Our results showed a hyperphosphorylation of titin in limb SKM, based on enhanced phosphorylation at the PEVK region, which is known to lead to titin filament stiffening. This hyperphosphorylation could be reversed by high-intensity interval training (HIIT). Additionally, a negative correlation occurring between the phosphorylation state of titin and the muscle force in the limb SKM was evident. For the Dia, no alterations in the phosphorylation state of titin could be detected. Supported by data of previous studies, this suggests an exercise effect of the Dia in HFpEF. Regarding the expression of contraction regulating proteins, significant differences between Dia and limb SKM could be detected, supporting muscle atrophy and dysfunction in limb SKM, but not in the Dia. Altogether, these data suggest a correlation between titin stiffening and the appearance of exercise intolerance in HFpEF, as well as a differential regulation between different SKM groups.

The ratio of parasternal intercostal muscle-thickening fraction-to-diaphragm thickening fraction for predicting weaning failure.

BACKGROUND: Diaphragm dysfunction is associated with weaning outcomes in mechanical ventilation patients, in the case of diaphragm dysfunction, the accessory respiratory muscles would be recruited. The main purpose of this study is to explore the performance of parasternal intercostal muscle thickening fraction in relation to diaphragmatic thickening fraction ratio (TFic1/TFdi2) for predicting weaning outcomes, and compare its accuracy with D-RSBI in predicting weaning failure. MATERIALS AND METHODS: We prospectively enrolled consecutive patients from 7/2022-5/2023. We measured TFic, TFdi, and diaphragmatic excursion (DE3) by ultrasound and calculated the TFic/TFdi ratio and diaphragmatic rapid shallow breathing index (D-RSBI4). Receiver-operator characteristic (ROC5) curves evaluated the accuracy of the TFic/TFdi ratio and D-RSBI in predicting weaning failure. RESULTS: 161 were included in the final analysis, 114 patients (70.8%) were successfully weaned from mechanical ventilation. The TFic/TFdi ratio (AUROC = 0.887 (95% CI: 0.821-0.953)) was superior to the D-RSBI (AUROC = 0.875 (95% CI: 0.807-0.944)) for predicting weaning failure. CONCLUSIONS: The TFic/TFdi ratio predicted weaning failure with high accuracy and outperformed the D-RSBI.

Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model.

Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model - the mdx mouse - is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function.

Aminophylline Improves Ventilator-Induced Diaphragmatic Dysfunction by Targeting IGF-1-FOXO1-MURF1 Pathway.

BACKGROUND: The usage of life-saving mechanical ventilation (MV) could cause ventilator-induced diaphragmatic dysfunction (VIDD), increasing both mortality and morbidity. Aminophylline (AP) has the potential to enhance the contractility of animal skeletal muscle fibers and improve the activity of human respiratory muscles, and the insulin-like growth factor-1 (IGF-1)- forkhead box protein O1 (FOXO1)-muscle RING finger-1 (MURF1) pathway plays a crucial role in skeletal muscle dysfunction. This study aimed to investigate the impact of AP on VIDD and to elucidate the role of the IGF-1-FOXO1-MURF1 pathway as an underlying mechanism. METHODS: Rat models of VIDD were established through MV treatment. IGF-1 lentiviral (LV) interference (LV-IGF-1-shRNA; controlled by lentiviral negative control LV-NC) was employed to inhibit IGF-1 expression and thereby block the IGF-1-FOXO1-MURF1 pathway. Protein and mRNA levels of IGF-1, FOXO1, and MURF1 were assessed using western blot and real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), respectively. Diaphragm contractility and morphometry were examined through measurement of compound muscle action potentials (CMAPs) and hematoxylin and eosin (H&E) staining. Oxidative stress was evaluated by levels of hydrogen peroxide (H2O2), superoxide dismutase (SOD), antioxidant glutathione (GSH), and carbonylated protein. Mitochondrial stability was assessed by measuring the mitochondrial membrane potential (MMP), and mitochondrial fission and mitophagy were examined through protein levels of dynamin-related protein 1 (DRP1), mitofusin 2 protein (MFN2), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), and Parkin (western blot). Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay and levels of Bax, B-cell lymphoma 2 (BCL-2), and Caspase-3. Levels of Atrogin-1, neuronally expressed developmentally downregulated 4 (NEDD4), and muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1) mRNA, as well as ubiquitinated protein, were utilized to determine protein degradation. Furthermore, the SUnSET (surface sensing of translation) method was employed to determine rates of protein synthesis. RESULTS: MV treatment upregulated IGF-1 while downregulated FOXO1 and MURF1 (p < 0.05). AP administration reversed IGF-1, FOXO1 and MURF1 (p < 0.05), which was suppressed again by IGF-1 inhibition (p < 0.05), demonstrating the blockage of the IGF-1-FOXO1-MURF1 pathway. MV treatment caused decreased CMAP and cross-sectional areas of diaphragm muscle fibers, and increased time course of CMAP (p < 0.05). Additionally, oxidative stress, cell apoptosis, and protein degradation were increased and mitochondrial stability was decreased by MV treatment (p < 0.05). Conversely, AP administration reversed all these changes induced by MV, but this reversal was disrupted by the blockage of the IGF-1-FOXO1-MURF1 pathway. CONCLUSIONS: In this study, MV treatment induced symptoms of VIDD in rats, which were all effectively reversed by AP regulating the IGF-1-FOXO1-MURF1 pathway, demonstrating the potential of AP in ameliorating VIDD.

Protective role of pretreatment with Anisodamine against sepsis-induced diaphragm atrophy via inhibiting JAK2/STAT3 pathway.

There is an increasing tendency for sepsis patients to suffer from diaphragm atrophy as well as mortality. Therefore, reducing diaphragm atrophy could benefit sepsis patients' prognoses. Studies have shown that Anisodamine (Anis) can exert antioxidant effects when blows occur. However, the role of Anisodamine in diaphragm atrophy in sepsis patients has not been reported. Therefore, this study investigated the antioxidant effect of Anisodamine in sepsis-induced diaphragm atrophy and its mechanism. We used cecal ligation aspiration (CLP) to establish a mouse septic mode and stimulated the C2C12 myotube model with lipopolysaccharide (LPS). After treatment with Anisodamine, we measured the mice's bodyweight, diaphragm weight, fiber cross-sectional area and the diameter of C2C12 myotubes. The malondialdehyde (MDA) levels in the diaphragm were detected using the oxidative stress kit. The expression of MuRF1, Atrogin1 and JAK2/STAT3 signaling pathway components in the diaphragm and C2C12 myotubes was measured by RT-qPCR and Western blot. The mean fluorescence intensity of ROS in C2C12 myotubes was measured by flow cytometry. Meanwhile, we also measured the levels of Drp1 and Cytochrome C (Cyt-C) in vivo and in vitro by Western blot. Our study revealed that Anisodamine alleviated the reduction in diaphragmatic mass and the loss of diaphragmatic fiber cross-sectional area and attenuated the atrophy of the C2C12 myotubes by inhibiting the expression of E3 ubiquitin ligases. In addition, we observed that Anisodamine inhibited the JAK2/STAT3 signaling pathway and protects mitochondrial function. In conclusion, Anisodamine alleviates sepsis-induced diaphragm atrophy, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway.

Mucopolysaccharidosis (MPS IIIA) mice have increased lung compliance and airway resistance, decreased diaphragm strength, and no change in alveolar structure.

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. Changes in the amount, metabolism, and function of pulmonary surfactant, the substance that regulates alveolar interfacial surface tension and modulates lung compliance and elastance, have been reported in MPS IIIA mice. Here we investigated changes in lung function in 20-wk-old control and MPS IIIA mice with a closed and open thoracic cage, diaphragm contractile properties, and potential parenchymal remodeling. MPS IIIA mice had increased compliance and airway resistance and reduced tissue damping and elastance compared with control mice. The chest wall impacted lung function as observed by an increase in airway resistance and a decrease in peripheral energy dissipation in the open compared with the closed thoracic cage state in MPS IIIA mice. Diaphragm contractile forces showed a decrease in peak twitch force, maximum specific force, and the force-frequency relationship but no change in muscle fiber cross-sectional area in MPS IIIA mice compared with control mice. Design-based stereology did not reveal any parenchymal remodeling or destruction of alveolar septa in the MPS IIIA mouse lung. In conclusion, the increased storage of HS which leads to biochemical and biophysical changes in pulmonary surfactant also affects lung and diaphragm function, but has no impact on lung or diaphragm structure at this stage of the disease.NEW & NOTEWORTHY Heparan sulfate storage in the lungs of mucopolysaccharidosis type IIIA (MPS IIIA) mice leads to changes in lung function consistent with those of an obstructive lung disease and includes an increase in lung compliance and airway resistance and a decrease in tissue elastance. In addition, diaphragm muscle contractile strength is reduced, potentially further contributing to lung function impairment. However, no changes in parenchymal lung structure were observed in mice at 20 wk of age.

IGF-1 Regulates Skeletal Muscle Degradation and Remolding in Ventilator-Induced Diaphragmatic Dysfunction by Mediating FOXO1 Expression.

BACKGROUND: Mechanical ventilation (MV) sustains life in critically ill patients by providing adequate alveolar ventilation. However, prolonged MV could induce inspiratory muscle atrophy known as ventilator-induced diaphragmatic dysfunction (VIDD). Insulin-like growth factor (IGF)-1 has been proven to play crucial roles in regulating skeletal muscle size and function. Meanwhile, the forkhead box protein O1 (FOXO1) has been linked to muscle atrophy. This study aimed to explore the effect of IGF-1 on muscle degradation and remodeling in VIDD and delved into the association of the underlying mechanism involving FOXO1. METHODS: VIDD models were established by treating rats with MV. Adeno-associated virus (AAV) was used for transfection to construct IGF-1 and/or FOXO1 overexpressed rats. There were four groups in this study: normal rats (NC), normal rats with MV treatment (MV), IGF-1-overexpressed rats with MV treatment (MV+IGF-1), and rats overexpressing both IGF-1 and FOXO1 with MV treatment (MV+IGF-1+FOXO1). Protein levels were measured by western blot or enzyme-linked immunosorbent assay (ELISA), and mRNA levels were detected by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). IGF-1 and FOXO1 expression were validated by detecting mRNA and protein levels. Diaphragmatic muscle contractility and morphometry were tested using stimulating electrodes in conjunction with hematoxylin and eosin (H&E) staining. Interleukin (IL)-6 and carbonylated protein were used for evaluating muscle atrophy and oxidation, respectively. Protein degradation was determined by troponin-I level and tyrosine release. Apoptosis was assessed using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay, alongside markers like Bax, B-cell lymphoma 2 (BCL-2), and Cleaved Caspase-3. Atrogin-1, muscle RING finger 1 (MURF1), neuronally expressed developmentally downregulated 4 (NEDD4), muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1), and ubiquitinated protein was used to determine proteolysis. Additionally, protein synthesis was measured by assessing the rates of mixed muscle protein (MMP) and myosin heavy chain (MHC). RESULTS: MV treatment caused IGF-1 downregulation (p < 0.01) and FOXO1 upregulation (p < 0.01). The IGF-1 upregulation downregulated FOXO1 in the MV+IGF-1 group (p < 0.001) while IGF-1 and FOXO1 were both upregulated in the MV+IGF-1+FOXO1 group (p < 0.001). The treatment of MV decreased muscle contractility and cross-sectional areas of diaphragm muscle fibers (p < 0.01). Additionally, IL-6, troponin-1, tyrosine release, carbonylated protein, TUNEL positive nuclei, Bax, Cleaved Caspase-3, Atrogin-1, MURF1, neuronally expressed developmentally downregulated 4 (NEDD4), MUSA1, and ubiquitinated protein levels increased significantly in MV group (p < 0.001) while levels of BCL-2, fractional synthetic rate of MMP and MHC, and type I and type II MHC protein mRNA expression decreased in MV group (p < 0.001). All of these alterations were reversed in the MV+IGF-1 group (p < 0.01), while the IGF-1-induced reversion was disrupted in the MV+IGF-1+FOXO1 group (p < 0.01). CONCLUSIONS: IGF-1 may protect diaphragmatic muscles from VIDD-induced structural damage and function loss by downregulating FOXO1. This action suppresses muscle breakdown and facilitates muscle remodeling in diaphragmatic muscles affected by VIDD.

Post-mortem detection of a calcifying fibrous pseudotumor at a rare site-A case report.

ABSTRACT: We report the case of a 48 year old man brought-in-dead to the trauma unit following an alleged accidental fall from a multi-storied building. Autopsy findings were consistent with traumatic injuries to the head, chest and spine. Incidentally, a bit of the diaphragm with a pearly white lobulated mass over the pleural surface was observed. Histopathological examination detected a calcifying fibrous pseudotumour (CFPT), confirmed by positive immunostaining for cluster of differentiation protein-34 (CD34) and vimentin (focally). CFPTs are slow-growing pseudotumours that are clinically benign with extremely low rate of recurrence and this might just be the first reported case of CFPT on the diaphragm. This shall further aid clinicians to diagnose these rare yet significant soft tissue tumors in uncommon sites.

Diaphragm endometriosis: Random localization or extended form of pelvis endometriosis. A large comparative analysis of 202 cases.

OBJECTIVE: The aim of this study was to investigate and present the clinical characteristics of diaphragm endometriosis, to approach the pathogenetic mechanisms, and to answer the question of whether this disease can be considered an extended form of pelvic endometriosis. STUDY DESIGN: It was a retrospective comparative one-to-one analysis of 202 cases. Two groups of patients were compared: Group 1 patients with diaphragm endometriosis vs Group 2 (control group) with pelvis endometriosis, each with 101 patients. RESULTS: Patients with diaphragm endometriosis had extreme significantly higher prevalence of severe pelvis endometriosis included deep infiltrated endometriosis and severe adhesions in term of complete Douglas obliteration (p value = 0.0001). There was neither age nor BMI difference in two groups. Besides of cyclic shoulder or upper abdomen pain there was no difference of symptoms. CONCLUSION: Diaphragm endometriosis is a rare condition with an approximate prevalence of 1.1% of all endometriosis cases. Since the symptoms are very specific and patients do not associate the pain with diaphragmatic endometriosis, the symptoms should be asked about explicitly. If patients with diaphragmatic endometriosis have no symptoms, the lesions do not necessarily need to be removed. The pathogenesis is still unclear. The authors of this study consider this disease to be an extended form of severe pelvic and deep infiltrated endometriosis. However, the right-side dominance still cannot be explained. Further research is needed to fully understand the origin of diaphragmatic endometriosis.

Combined ultrasound of m. quadriceps and diaphragm to determine the occurrence of sarcopenia and prolonged ventilation in a COVID-19 ICU cohort: The COVID-SARCUS trial.

OBJECTIVE: The aim of this study was to determine the development of sarcopenia in a COVID-19 intensive care unit population by sequential quadriceps and diaphragm ultrasound and its relationship with hospital outcomes. METHODS: We assessed muscle thickness, cross-sectional area, fascicle length, pennation angle, and echo intensity within 48 h after intubation, at days 5 and 10 and at discharge from the intensive care unit in 30 critically ill patients with confirmed COVID-19. RESULTS: A different evolution of muscle thickness of the diaphragm and m. rectus femoris was observed; the changes between the two muscles were not correlated (Pearson's χ2 3.91, P = 0.419). The difference in muscle thickness was linked to the outcome for both m. rectus femoris and diaphragm, with the best survival seen in the group with stable muscle thickness. The greatest loss of muscle thickness occurred between days 5 and 10. The echo intensity was higher in the patients with increased muscle thickness, who also had a worse prognosis. There was a correlation between cross-sectional area on day 5 and handgrip strength (r = 0.290, P = 0.010). Only 31% of patients were able to return to their preadmission residence without any additional rehabilitation. CONCLUSIONS: Muscle atrophy and decline in muscle strength appear in the earliest stages after admission to the intensive care unit and are related to functional outcome.

Supragastric lesser sac: an insidious site for surgical exploration during the debulking surgery in advanced ovarian cancer.

OBJECTIVE: Metastases in the supragastric lesser sac (SGLS) are not only occult but are also barriers to complete resection of ovarian cancer. We describe a cohort of patients with SGLS disease undergoing debulking surgery. METHODS: We identified all patients who underwent evaluation and eventual resection of SGLS disease as part of cytoreductive surgery for stage IIIC-IVB high-grade epithelial ovarian cancer at our institution from January 2018 to August 2022. RESULTS: Thirty-three of 286 patients (11.5%) underwent resection of SGLS disease. Metastases in the SGLS were identified by preoperative imaging in 4 of 33 patients (12.1%). The median peritoneal cancer index score was 22 (range, 9-33). Through surgical exploration, metastases were frequently seen in the right diaphragm (100%), hepatorenal recess (97%), lesser omentum (81.8%), left diaphragm (78.8%), supracolic omentum (75.8%), anterior transverse mesocolon (72.7%), splenic hilum (63.6%), ligamentum teres hepatis (60.6%), and gallbladder fossa (51.5%). The lesser omentum was normal in 6 of 33 (18.2%) patients, despite metastases within the SGLS. A total of 54.5% of patients underwent complex surgery (surgical complexity scores; median, 8; range, 3-14). Complete resections were achieved in 19 (57.6%) patients. No complications were related to the resection of SGLS disease. The median length of progression-free survival was 24.8 months (95% confidence interval=16.6-32.9). CONCLUSION: Metastases to the SGLS are not uncommon in advanced ovarian cancer, particularly those with widely disseminated disease. Disease in this recess is rarely identified by preoperative imaging and deserves systematic surgical exploration to attain complete cytoreduction.

[A Case of Palliative Laparoscopic Surgery in an Older Woman with Advanced Gastric Cancer and a Large Hiatal Hernia].

A 94-year-old woman presented with anorexia, persisting for several months, and marked anemia. An upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer in the antrum. CT imaging indicated a large esophageal hiatus hernia and the elevation of the gastric fornix to the level of the bronchus. Wall thickening in the antrum, surrounded by increased fat tissue density, and swollen lymph nodes along the common hepatic artery, were detected. She was diagnosed with advanced gastric cancer(cT3N1M0, cStage Ⅲ)and a large hiatal hernia. A laparoscopic hiatal hernia repair and distal gastrectomy were performed. The cancer was exposed outside the serosa in the antrum, yet there was no indication of ascites, liver metastasis or peritoneal dissemination. The esophageal hiatus was sutured, and a distal gastrectomy(Billroth-Ⅱ reconstruction)was conducted. To avert hernia recurrence, sutures were applied to the posterior wall of the abdominal esophagus and the crus of the diaphragm, as well as the fornix of the remnant stomach and the diaphragm. Her postoperative course was uneventful, and she was discharged on POD13. There were no instances of gastric cancer recurrence or hiatal hernia 7 months post-operation.

Outcomes in critically ill patients after diaphragmatic stimulation on ventilator-induced diaphragmatic dysfunction: a systematic review.

INTRODUCTION: Mechanical ventilation (MV) is a lifesaving procedure for critically ill patients. Diaphragm activation and stimulation may counteract side effects, such as ventilator-induced diaphragm dysfunction (VIDD). The effects of stimulation on diaphragm atrophy and patient outcomes are reported in this systematic review. EVIDENCE ACQUISITION: Studies investigating diaphragmatic stimulation versus standard of care in critically ill patients and evaluating clinical outcomes were extracted from a Medline database last on January 23, 2023, after registration in Prospero (CRD42021259353). Selected studies included the investigation of diaphragmatic stimulation versus standard of care in critically ill patients, an evaluation of the clinical outcomes. These included muscle atrophy, VIDD, weaning failure, mortality, quality of life, ventilation time, diaphragmatic function, length of stay in the Intensive Care Unit (ICU), and length of hospital stay. All articles were independently evaluated by two reviewers according to their abstract and title and, secondly, a full texts evaluation by two independent reviewers was performed. To resolve diverging evaluations, a third reviewer was consulted to reach a final decision. Data were extracted by the reviewers following the Oxford 2011 levels of evidence guidelines and summarized accordingly. EVIDENCE SYNTHESIS: Seven studies were extracted and descriptively synthesized, since a metanalysis was not feasible. Patients undergoing diaphragm stimulation had moderate evidence of higher maximal inspiratory pressure (MIP), less atrophy, less mitochondrial respiratory dysfunction, less oxidative stress, less molecular atrophy, shorter MV time, shorter ICU length of stay, longer survival, and better SF-36 scores than control. CONCLUSIONS: Evidence of the molecular and histological benefits of diaphragmatic stimulation is limited. The results indicate positive clinical effects of diaphragm activation with a moderate level of evidence for MIP and a low level of evidence for other outcomes. Diaphragm activation could be a therapeutic solution to avoid diaphragm atrophy, accelerate weaning, shorten MV time, and counteract VIDD; however, better-powered studies are needed to increase the level of evidence.

Periquistectomía laparoscópica para quiste hidatídico del segmento VIII con compromiso del diafragma / Laparoscopic pericystectomy for segment VIII hydatid cyst of the liver with diaphragmatic compromiso

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Efectos morfológicos y mecánicos en ratas Sprague Dawley sometidas a ciclos de hipoxia / Morphological and mechanical effects in Sprague Dawley rats subjected to hypoxia cycles

Periodos extensos de hipoxia provocan cambios adaptativos que permiten responder a las demandas impuestas por el ambiente. Sin embargo, existen casos donde esta exposición es intermitente, como es el caso de los trabajadores en zonas andinas. El objetivo de esta comunicación fue comprobar los efectos morfológicos y mecánicos en diafragma y pulmones de ratas sometidas a la hipoxia intermitente. Se utilizaron 4 ratas Sprague Dawley de 6 meses de edad. Dos ratas fueron sometidas a 10 ciclos de hipoxia hipobárica intermitente (HHI) de 96 h (~428 torr; PO2 90 mm Hg), seguidos de 96 h de normoxia normobárica, durante 80 días. Se realizaron pruebas tracción uniaxial y de tinción con HematoxilinaEosina y Picrosirius red de Junqueira. Al comparar las curvas de los diafragmas, los sometidos a hipoxia reducen levemente su esfuerzo respecto a la condición de normoxia, en el tejido pulmonar la hipoxia afecta negativamente su resistencia, estas muestran una pendiente menor respecto a las normóxicas. En el análisis histológico, el parénquima pulmonar presentó menor cantidad de vasos sanguíneos y celularidad, como una mayor fracción de área de los espacios alveolares y cantidad de colágeno total en el grupo HHI. En el diafragma, el grupo HHI presentó menor cantidad de miocitos distribuidos irregularmente y de colágeno total. En conclusión, los principales hallazgos indican que el diafragma y el tejido pulmonar sometido a HHI sufren cambios estructurales, que se traducen en una disminución en su capacidad de resistencia tensil.

Extensive periods of hypoxic cause adaptive changes that make it possible to respond to the demands imposed by the environment. However, there are cases where this exposure is intermittent, as is the case of workers in andean areas. The objective of this communication was to verify the morphological and mechanical effects on diaphragm and lungs of rats subjected to intermittent hypoxic. Four 6-monthold Sprague Dawley rats were used. Two rats were subjected to 10 cycles of intermittent hypobaric hypoxic (IHH) of 96 h (~428 torr, PO2 90 mm Hg), followed by 96 h of normobaric normoxia, for 80 days. Uniaxial traction and staining tests were performed with Hematoxylin-Eosin and Picrosirius red de Junqueira. When comparing the curves of the diaphragms, those subjected to hypoxic slightly reduce their effort with respect to the condition of normoxia, in the lung tissue the hypoxic negatively affects its resistance, these show a lower slope with respect to the normoxics. In the histological analysis, the pulmonary parenchyma had a lower number of blood vessels and cellularity, such as a greater area fraction of alveolar spaces and amount of total collagen in IHH group. In the diaphragm, IHH group had a lower number of irregularly distributed myocytes and a lower amount of total collagen. In conclusion, the main findings indicate that the diaphragm and lung tissue subjected to IHH undergo structural changes, which result in a decrease in tensile strength.