Abdominal pseudohernia: causes and surgical management

Traumatic nerve injury or nerve disease leads to denervation and severe muscle atrophy. Recent evidence shows that mitochondrial loss could be a key mediator of skeletal muscle atrophy. Here, we show that daily heat stress treatment rescues denervation-induced loss of mitochondria and concomitant muscle atrophy. We also found that denervation-activated autophagy-dependent mitochondrial clearance (mitophagy) was suppressed by daily heat stress treatment. The molecular basis of this observation is explained by our results showing that heat stress treatment attenuates the increase of key proteins that regulate the tagging step for mitochondrial clearance and the intermediate step of autophagosome formation in denervated muscle. These findings contribute to the better understanding of mitochondrial quality control in denervated muscle from a translational perspective and provide a mechanism behind the attenuation of muscle wasting by heat stress. Traumatic nerve injury or motor neuron disease leads to denervation and severe muscle atrophy. Recent evidence indicates that loss of mitochondria and the related reduction in oxidative capacity could be key mediators of skeletal muscle atrophy. As our previous study showed that heat stress increased the numbers of mitochondria in skeletal muscle, we evaluated whether heat stress treatment could have a beneficial impact on denervation-induced loss of mitochondria and subsequent muscle atrophy. Here, we report that daily heat stress treatment (mice placed in a chamber with a hot environment; 40°C, 30minday(-1) , for 7days) rescues the following parameters: (i)muscle atrophy (decreased gastrocnemius muscle mass); (ii)loss of mitochondrial content (decreased levels of ubiquinol-cytochrome c reductase core proteinII, cytochrome c oxidase subunitsI and IV and voltage-dependent anion channel protein); and (iii)reduction in oxidative capacity (reduced maximal activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase) in denervated muscle (produced by unilateral sciatic nerve transection). In order to gain a better understanding of the above mitochondrial adaptations, we also examined the effects of heat stress on autophagy-dependent mitochondrial clearance (mitophagy). Daily heat stress normalized denervation-activated induction of mitophagy (increased mitochondrial microtubule-associated protein 1A/1B-light chain3-II (LC3-II) with and without blocker of autophagosome clearance). The molecular basis of this observation was explained by the results that heat stress attenuated the denervation-induced increase in key proteins that regulate the following steps: (i)the tagging step of mitochondrial clearance (increased mitochondrial Parkin, ubiquitin-conjugated, P62/sequestosome 1 (P62/SQSTM1)); and (ii)the elongation step of autophagosome formation (increased Atg5-Atg12 conjugate and Atg16L). Overall, our results contribute to the better understanding of mitochondrial quality control and the mechanisms behind the attenuation of muscle wasting by heat stress in denervated skeletal muscle.

Herpes zoster (HZ) is the reactivation of the varicella-zoster virus and usually causes unilateral dermatomal vesicles; deep tissue involvement is uncommon. We report a 76-year-old man who, 12 days after classic right-flank HZ in the T11 dermatome, developed a painless right-sided abdominal bulge. Examination found a soft, non-pitting swelling. Computed tomography demonstrated ipsilateral thinning of the abdominal wall muscles without evidence of a fascial defect, true hernia, or mass, consistent with zoster-related segmental motor neuropathy presenting as an abdominal pseudohernia. He was managed conservatively with reassurance; no surgery was required. This case highlights a rare neuromuscular complication of HZ and supports the use of imaging in unexplained post-zoster abdominal swelling.

The results of various biochemical examinations in 14 patients with cirrhosis (6 males and 8 females) with muscle atrophy at the thenar and hypothenar eminence (muscle atrophy group; mAG) were compared with those in 13 patients (8 males and 5 females) with cirrhosis without muscle atrophy at these sites (non-muscle atrophy group; NmAG). All patients were elderly men and women (mAG and NmAG, mean age, 69 +/- 3 years and 60 +/- 7, respectively). In most mAG patients, muscle atrophy was accompanied by palmar erythema. Muscle atrophy was histologically demonstrated by biopsy. Furthermore, electromyography and magnetic resonance study of the cervical spinal cord revealed that the atrophy was of myogenic rather than neurogenic origin. The Child-Pugh score, body mass index and sex hormone level in urine (total 24 h) in the two groups were compared along with the biochemical results. There were no significant differences between the two groups in urine estrogen and testosterone levels. The urinary creatinine excretion was significantly reduced in mAG. The creatine phosphokinese, lactate dehydrogenase isoenzyme and aldolase levels in serum did not differ significantly in the two groups, whereas the serum albumin level was significantly increased in NmAG. Significant differences were observed only for the serum albumin level, age and body mass index. Thus, we consider that palmar muscle atrophy in patients with cirrhosis is not due to hormonal excess in serum, but may be attributable to advanced age and diminished physical strength.

The patients with chronic obstructive pulmonary disease (COPD) generally have malnutrition and different level's skeletal muscle atrophy, low body mass and skeletal muscle wasting not only induce peripheral skeletal muscle dysfunction, respiratory muscle's acratia, exercise in tolerance and reduction of life quality in patients with COPD, but also heavily influence its prognosis and case fatality rate. Through uninterrupted comprehend pathogenesy of skeletal muscle atrophy in COPD, we can do some effective intervention to malnutrition and skeletal muscle atrophy in patients with COPD, and we can improve,even prevent this pathologic state, consequently improre life quanlity and decrease death rate of patients with COPD. Key words: Chronic obstructive pulmonary disease; Skeletal muscle; Atrophy; Pathogenesis

Skeletal muscle wasting is a critical clinical challenge in patients with breast cancer treated with chemotherapy, given its correlation with increased mortality risk and decreased therapeutic efficacy. However, the mechanisms underlying this side effect remain poorly understood, slowing the development of effective preventive strategies. Here, we conducted a translational study using an innovative multimodal experimental design to comprehensively investigate the mechanisms driving chemotherapy-induced muscle atrophy. We analyzed 72 samples from 36 patients with breast cancer across four experimental groups at various time points during chemotherapy, complemented by in vitro experiments. Through histological, transcriptomic, targeted protein expression, and activity-based analyses, we identified NF-κB signaling and the subsequent upregulation of the ubiquitin-proteasome system as drivers of chemotherapy-induced muscle atrophy. In vitro, sulfasalazine effectively mitigated the imbalance in protein turnover and fully prevented muscle atrophy, offering promising perspectives for clinical translation and improving patient prognosis.NEW & NOTEWORTHY By combining acute and chronic muscle biopsies from patients with breast cancer with complementary in vitro experiments, we determined that breast cancer chemotherapy triggers a rapid skeletal muscle atrophy driven by NF-κB activation and subsequent upregulation of the ubiquitin-proteasome system. Importantly, sulfasalazine fully prevented muscle atrophy by mitigating the imbalance in protein turnover, offering promising perspectives for clinical translation and improving patient prognosis.

BackgroundMuscle atrophy is a typical affliction in patients affected by knee Osteoarthritis (KOA). This study aimed to examine the potential pathogenesis and biomarkers that coalesce to induce muscle atrophy, primarily through the utilization of bioinformatics analysis.MethodsTwo distinct public datasets of osteoarthritis and muscle atrophy (GSE82107 and GSE205431) were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA) to probe for common differentially expressed genes (DEGs) and conduct transcription factor (TF) enrichment analysis from such genes. Venn diagrams were used to identify the target TF, followed by the construction of a protein-protein interaction (PPI) network of the common DEGs governed by the target TF. Hub genes were determined through the CytoHubba plug-in whilst their biological functions were assessed using GSEA analysis in the GTEx database. To validate the study, reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry techniques were employed.ResultsA total of 138 common DEGs of osteoarthritis and muscle atrophy were identified, with 16 TFs exhibiting notable expression patterns in both datasets. Venn diagram analysis identified early growth response gene-1 (EGR1) as the target TF, enriched in critical pathways such as epithelial mesenchymal transition, tumor necrosis factor-alpha signaling NF-κB, and inflammatory response. PPI analysis revealed five hub genes, including EGR1, FOS, FOSB, KLF2, and JUNB. The reliability of EGR1 was confirmed by validation testing, corroborating bioinformatics analysis trends.ConclusionsEGR1, FOS, FOSB, KLF2, and JUNB are intricately involved in muscle atrophy development. High EGR1 expression directly regulated these hub genes, significantly influencing postoperative muscle atrophy progression in KOA patients.

Background Latrogenic, traumatic, infectious or any other pathologic reason causing temporary or permanent denervation of a segment of the muscle of the abdominal wall may result in a protrusion of a group of muscles clinically evident as a hernia, but if there is no muscle or fascial defect, then it is categorized as pseudo hernia. Aim To report a case of a 53-year-old man with a history of Multiple Sclerosis (MS) and scoliosis who presented for evaluation of a painless protrusion of his left abdominal wall flank with exacerbation on upright position. Abdominal computed tomography did not reveal any herniation of abdominal contents, but magnetic resonance imaging of chest and abdomen showed a protrusion of a herniated soft disc at the T11–T12 neural foramen. Rest and non-steroidal anti-inflammatory drugs were prescribed, and the patient was followed for six months with resolution of his pseudohernia. Conclusion This case presents a rare instance of abdominal pseudohernia due to T11–T12 radiculopathy. Though MS is characterized by central nervous system, there are some references for peripheral nerve damage. In our case, due to the temporary feature of denervation and the complete restoration of function, there is no doubt that radiculopathy was the cause.

The 2 years 5 months patient diagnosed with a congenital deformity of the spine (posterolateral hemivertebra) underwent extraction of the hemivertebra from the retroperitoneal approach. In the postoperative period, a pseudohernial protrusion of the anterior abdominal wall was observed. 4.5 months later the protrusion resolved spontaneously. Abdominal wall relaxation is studied worldwide and is presented primarily as clinical case reports, mainly in older patients with neurological diseases. Single cases of this pathology are described among children. The Th10-Th12 roots are most often affected. Possible manifestations include: bloating and abdominal pain, pseudo-obstruction of the small and/or large intestine, and constipation. In the described case, only unilateral bloating at rest was observed, which increased with crying and strain. The natural course and prognosis of this diagnosis are usually favorable-the recovery period, according to the literature, takes an average of 4-5 months, which also coincided with our case. Pseudohernias are a rare complication and may can occur during correction of spinal deformities in children. This condition is a transient disorder of the anterior abdominal wall muscles, the cause of which may be neuropathy caused by infection, metabolic disorders, or mechanical damage. The main principles of treatment of this condition include active observation and symptomatic therapy. The prognosis is usually favorable.

Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.

ANY part of the pleura-covered lung which protrudes beyond the normal boundaries of the thoracic cage and invades the subcutaneous tissues can rightfully be designated as a true hernia. True lung hernia should not be confused with evisceration or prolapse, an error not infrequently made by early writers. Lung hernia is a very rare condition; up to the present time, less than 200 cases have been reported in the literature. Because of its rarity, clinicians of wide experience have had little opportunity to observe it. Much information in the literature is inaccurate and confusing and, therefore, some early reports are not dependable. Several names have been applied to lung hernia, as pneumonocele, pneumocele, and pulmonary hernia. Considering the great number of stab and bullet wounds in warfare and civilian life, and crushing injuries of the chest, it is surprising that lung hernia is not more frequent. In an extensive war experience with chest wounds, Makins observed one case, while Adams reported five out of 20,000 chest wounds in the Russian-Japanese War (1). It is also noteworthy that, with frequent fractures of the ribs, pneumothorax rarely occurs. In a study of 89 cases of fractured ribs requiring hospitalization, 16 were treated for other complications but only one instance occurred in which pneumothorax resulted (2). History As early as 1891, Rolandus published a report of the first case operated upon for lung hernia (3). Chassier mentions herniated lung and was one of the first to accord it special consideration (4). Cloquet, in 1819, reported a case of a young man, age 32 years, crushed under a gun carriage, who made a good recovery (5). Morel-Lavallée, who collected 32 cases, gave us a very comprehensive classification (6). Lake mentions a case of lung hernia caused by the handle of a wheelbarrow penetrating the side of the chest (7). Dufour reports a case of traumatic hernia cured without operation, after much loss of blood (8). In 20,000 wounds in the War of the Rebellion, only seven lung hernias were reported. Cockle published a case of double pulmonary hernia (9). Lewtas (10) and Hirschsprung (11) each reported a case of congenital hernia. Spontaneous pneumocele from violent exertion in weight lifting was reported by Masoti (12). Hagentorn (13) mentions pneumotomy in pneumocele. In 1893, Pitt (14) affirmed that the protrusion of hernia may occur at the time of trauma or any time later. Lopez (15) reported resection of the lung for hernia, with recovery. Tuffier (16) mentions resection of the lung and Knox (17) reported two cases of hernia of the lung into the neck. From 1895 to 1904 several cases of hernia of the lung and its treatment were reported (18, 19, 20, 21, 22). Vulpius (23) reported a case of traumatic hernia of the lung which, five weeks after plastic operation, was discharged, cured.

Objective To explore the effect of delaying atrophy of mice denervated skeletal muscles by lentivirus mediated gene transfer of cardiotrophin-1. Methods Thirty-six Swiss mice were randomly divided into experimental group and control group, with 18 each. A model of gastrocnemius muscle denervation atrophy was established at the right lower limb by transecting the tibial nerve. Deaervated gastrocnemius muscles of the experimental group and control group were administered with 20 μl ( 108 TU/ml) of recombinant lentivirus vector carrying CT-1 eDNA and with 20 μl of Lenti-GFP solution respectively. Two and 4 weeks following the transfection, 3 mice each were checked for transection efficacy by observing expression of green fluorescent protein (GFP) under fluorescent microscope. Westem blot assays were done to validate the expression of CT-1.Twitch tension and tetanie tension, muzzle wet weight preservation rate, muscle fiber cross-sectional area and ultrastruture of the denervated muscles were measured and observed in 6 mice at each timepoint to evaluate the extent of muscle atrophy. Results Strong GFP expression was observed in the gastrocnemius muscles of both groups at 2 and 4 weeks following lentivirus transfeetion. Westem blot showed significantly inereaticl expression of CT-1 in the experimental group compared with the control group ( P < 0.01 ). Two weeks after transfection,twitch tension and tetanic tension, muscle wet weight preservation rate and muscle fiber cross-sectional area of the denervated muscles in the experimental group were (47.61 ± 6.25) %, (56.08 ± 5.47) %, (63.02 ± 5.23) %and (1372.42+ 149.73)μm2 respectively, being significantly higher than those in the control group, which were (27.23±5.06)%,(30.78±4.67)%,(52.41±4.98)%and(1147.28±128.67)μm2 respectively(all P <0.01).At 4 weeks.the above-mendoned parameters were(33.13±4.76)%,(36.59 4-5.67)%.(51.46-±5.36)%,and(1209.12±142.57)μm2 respectively in the experimental group,being significantly greater than these in the control group which were(16.40±5.48)%,(15.35±4.08)%,(39.15±6.12)%and (989.45 4-136.12)μm2 respectively(all P<0.01).Dilation of the sareoplasmic refieulum of denervated muscles in the experimental group wss markedly alleviated.Conclusion Lentivirus mediated gene therapy can aehieve high transection efficacy.CT-1 gene tmnsfeefion call produce llighly egieient and sustained CT-1 secretion in vivo and delay denervation indueed skeletal muscle atrophy for at least 4 weeks. Key words: ]Muscular atrophy; Denervation; Cardiotrophin-1

DKK3 as a diagnostic marker and potential therapeutic target for sarcopenia in chronic obstructive pulmonary disease

Introduction: Peripheral artery disease (PAD) is characterized by atherosclerosis of lower extremity arteries that promotes reduced muscle perfusion and skeletal muscle atrophy, which contributes to functional impairment in PAD patients. Computed tomography (CT) imaging offers a non-invasive method for quantifying peripheral muscle characteristics; however, manual image segmentation of muscles is time-consuming, and regional muscle analysis remains understudied in PAD. Therefore, we sought to develop and validate a deep learning approach for calf muscle segmentation to assess serial regional changes in muscle density of PAD patients over an 18-month study period. Methods: Patients with PAD (n=89) were prospectively enrolled for lower extremity non-contrast CT imaging. A subset of patients (n=45) was recruited for an additional follow-up CT scan 18 months later. Calf muscle groups, including the gastrocnemius, soleus, and tibialis anterior, were manually segmented from axial CT images of each patient’s symptomatic limb, and mean muscle densities for each muscle were quantified based on CT Hounsfield units. Manual segmentations were used to train an nnU-Net deep learning model. Data augmentation techniques were performed to enhance generalization. The dataset was split into an 80/20 ratio for the training and test sets. Dice coefficients were calculated to evaluate the overlap/agreement between manual and deep learning segmentations. Paired t-tests were performed to assess the differences in muscle densities between the baseline and 18-month follow-up measures. Results: The deep learning model achieved high segmentation performance, with dice scores of 0.90 ± 0.02 for the gastrocnemius and soleus, and 0.89 ± 0.02 for the tibialis anterior. Deep learning-guided serial CT image analysis detected a significant reduction in muscle densities across all muscle groups at 18-month follow-up when compared to baseline measurements (p&lt;0.05). Conclusion: Deep learning analysis can enable rapid, regional analysis of lower extremity skeletal muscle characteristics, reducing the time for muscle-by-muscle analysis in PAD patients from hours to seconds. Future implementation of regional muscle analysis in PAD may assist vascular medicine specialists with identifying regional muscle wasting that is related to patient walking impairment and/or symptoms as well as aid in serial monitoring of PAD patients following revascularization or supervised exercise for claudication.

Backgroundp38 mitogen-activated protein kinase has been implicated in both skeletal muscle atrophy and hypertrophy. T317 phosphorylation of the p38 substrate mitogen-activated protein kinase-activated protein kinase 2 (MK2) correlates with muscle weight in atrophic and hypertrophic denervated muscle and may influence the nuclear and cytoplasmic distribution of p38 and/or MK2. The present study investigates expression and phosphorylation of p38, MK2 and related proteins in cytosolic and nuclear fractions from atrophic and hypertrophic 6-days denervated skeletal muscles compared to innervated controls.MethodsExpression and phosphorylation of p38, MK2, Hsp25 (heat shock protein25rodent/27human, Hsp25/27) and Hsp70 protein expression were studied semi-quantitatively using Western blots with separated nuclear and cytosolic fractions from innervated and denervated hypertrophic hemidiaphragm and atrophic anterior tibial muscles. Unfractionated innervated and denervated atrophic pooled gastrocnemius and soleus muscles were also studied.ResultsNo support was obtained for a differential nuclear/cytosolic localization of p38 or MK2 in denervated hypertrophic and atrophic muscle. The differential effect of denervation on T317 phosphorylation of MK2 in denervated hypertrophic and atrophic muscle was not reflected in p38 phosphorylation nor in the phosphorylation of the MK2 substrate Hsp25. Hsp25 phosphorylation increased 3-30-fold in all denervated muscles studied. The expression of Hsp70 increased 3-5-fold only in denervated hypertrophic muscles.ConclusionsThe study confirms a differential response of MK2 T317 phosphorylation in denervated hypertrophic and atrophic muscles and suggests that Hsp70 may be important for this. Increased Hsp25 phosphorylation in all denervated muscles studied indicates a role for factors other than MK2 in the regulation of this phosphorylation.

Skeletal muscle is a highly plastic tissue. Overall muscle growth (hypertrophy) or muscle wasting (atrophy) results from alterations in intracellular signaling pathways with important regulatory steps occurring in the nucleus as well as in the cytoplasm. Previous studies have identified components of the Akt/mTor pathway as well as the p38 MAPK pathway as important for skeletal muscle hypertrophy and/or atrophy. The present study tests the hypothesis that MK2, a substrate of p38 which following phosphorylation, can be exported from the nucleus in a complex with p38, may be important for skeletal muscle growth. The expression of MK2 was examined in denervated mouse hind-limb (atrophic) and hemidiaphragm (transiently hypertrophic) muscles. MK2 mRNA expression decreased after denervation in both atrophic (48% of innervated controls, P < 0.001) and hypertrophic muscle (34% of innervated controls, P < 0.01) but MK2 protein expression decreased only in atrophic muscle (32% of innervated controls, P < 0.01). The level of T205 phosphorylated MK2 increased after denervation in both atrophic (fourfold increase, P < 0.01) and hypertrophic muscles (almost sevenfold increase, P < 0.001) whereas the level of T317 phosphorylated MK2 (necessary for nuclear export) increased after denervation in hypertrophic muscle (nearly threefold increase, P < 0.001) but not in atrophic muscle. Logarithmically transformed relative changes in MK2 phosphorylated at T317 correlated well (r(2) = 0.7737) with relative changes in muscle weight. The results suggest a role for MK2 in the regulation of muscle mass, a role which, at least in part, may be related to determining the subcellular localization of p38 in muscle fibers.