Tendon healing is adversely affected by low-grade inflammation

Background Tendinopathy is common, presents with pain and activity limitation, and is associated with a high risk of recurrence of the injury. Tendinopathy usually occurs as a results of a disrupted healing response to a primary injury where cellular and molecular pathways lead to low grade chronic inflammation. Main findings There has been a renewed interest in investigating the role of Inflammation in the pathogenesis of tendinopathy, in particular during the initial phases of the condition where it may not be clinically evident. Understanding the early and late stages of tendon injury pathogenesis would help develop new and effective treatments addressed at targeting the inflammatory pathways. Conclusion This review outlines the role of low-grade Inflammation in the pathogenesis of tendinopathy, stressing the role of proinflammatory cytokines, proteolytic enzymes and growth factors, and explores how Inflammation exerts a negative influence on the process of tendon healing.

Microstructural Tissue Changes in a Rat Model of Mild Traumatic Brain Injury

Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats after mild traumatic brain injury (mTBI). The brains of sham-operated and mTBI rats 35 days after lateral fluid percussion injury were imaged ex vivo in a 11.7-T scanner. Voxel-based analyses of DTI-, fixel- and NODDI-based metrics detected extensive tissue changes in directly affected brain areas close to the primary injury, and more importantly, also in distal areas connected to primary injury and indirectly affected by the secondary injury mechanisms. Histology revealed ongoing axonal abnormalities and inflammation, 35 days after the injury, in the brain areas highlighted in the group analyses. Fractional anisotropy (FA), fiber density (FD) and fiber density and fiber bundle cross-section (FDC) showed similar pattern of significant areas throughout the brain; however, FA showed more significant voxels in gray matter areas, while FD and FDC in white matter areas, and orientation dispersion index (ODI) in areas most damage based on histology. Region-of-interest (ROI)-based analyses on dMRI maps and histology in selected brain regions revealed that the changes in MRI parameters could be attributed to both alterations in myelinated fiber bundles and increased cellularity. This study demonstrates that the combination of dMRI methods can provide a more complete insight into the microstructural alterations in white and gray matter after mTBI, which may aid diagnosis and prognosis following a mild brain injury.

Hematogenous Macrophages: A New Therapeutic Target for Spinal Cord Injury

Spinal cord injury (SCI) is a devastating disease leading to loss of sensory and motor functions, whose pathological process includes mechanical primary injury and secondary injury. Macrophages play an important role in SCI pathology. According to its origin, it can be divided into resident microglia and peripheral monocyte-derived macrophages (hematogenous Mφ). And it can also be divided into M1-type macrophages and M2-type macrophages on the basis of its functional characteristics. Hematogenous macrophages may contribute to the SCI process through infiltrating, scar forming, phagocytizing debris, and inducing inflammatory response. Although some of the activities of hematogenous macrophages are shown to be beneficial, the role of hematogenous macrophages in SCI remains controversial. In this review, following a brief introduction of hematogenous macrophages, we mainly focus on the function and the controversial role of hematogenous macrophages in SCI, and we propose that hematogenous macrophages may be a new therapeutic target for SCI.

SYSCHRONOUS PRIMARY THYROID, LUNG AND COLON CANCERS: A CASE REPORT

Multiple primary neoplasms are relatively rare, but their incidence has increased because of aging and improvements in diagnostic imaging. There are many ways to classify, but nowadays, multiple primary cancers are again classified as synchronous and metachronous, the time is 6 months after the first primary injury detection, some authors get 12 months. Our clinical case is a 66-year-old man, prolonged exposure to risk factors for cancer. The patient was diagnosed with different types of primary cancer, colon cancer, thyroid cancer, lung cancer, and stomach cancer. The patient was treated according to the general clinical guidelines suitable for the disease type and the stage of the disease at the time of detection. Lesson learned is the importance of screening tests, attitudes, and comprehensive views of doctors for cancer patients, avoiding missing injuries, affecting the quality of treatment for patients.

Meat Hook Injury Leading to Brain Abscess: A Rare Occurrence

Transorbital orbitofrontal penetrating injury by a nonmissile object is uncommon. The presentation of this injury varies. This injury can be easily missed during the initial clinical presentation, because the foreign body is sometimes not visible on local examination, the wound on the orbital skin is small, and very subtle signs are present. The patient can present with delayed complications of the primary injury. Our patient was a 33-year-old male who presented with an orbitofrontal injury with a meat hook. He had minor symptoms at the time of presentation, which were overlooked. Three weeks later, he developed signs and symptoms of raised intracranial pressure (ICP). Brain imaging revealed a peripheral rim of contrast-enhancing mass lesion in the right frontal lobe, extending into the right orbit with perilesional edema suggestive of posttraumatic brain abscess. Via right frontal craniotomy, pus was drained out and abscess wall was excised. The patient made good clinical recovery. A higher index of suspicion and sound knowledge of occult penetrating injury patterns is required in the cases of orbital injuries. Appropriate radiological imaging can lead to an earlier and accurate diagnosis, and can prevent its delayed sequela like brain abscess.

Post Orgasmic Illness Syndrome (POIS) and Delayed Onset Muscle Soreness (DOMS): Do They Have Anything in Common?

Post orgasmic illness syndrome is a rare, mysterious condition with an unknown pathomechanism and uncertain treatment. The symptoms of post orgasmic illness syndrome last about 2–7 days after an ejaculation. The current hypothesis proposes that the primary injury in post orgasmic illness syndrome is an acute compression proprioceptive axonopathy in the muscle spindle, as is suspected in delayed onset muscle soreness. The terminal arbor degeneration-like lesion of delayed onset muscle soreness is theorized to be an acute stress response energy-depleted dysfunctional mitochondria-induced impairment of Piezo2 channels and glutamate vesicular release. The recurring symptoms of post orgasmic illness syndrome after each ejaculation are suggested to be analogous to the repeated bout effect of delayed onset muscle soreness. However, there are differences in the pathomechanism, mostly attributed to the extent of secondary tissue damage and to the extent of spermidine depletion. The spermidine depletion-induced differences are as follows: modulation of the acute stress response, flu-like symptoms, opioid-like withdrawal and enhanced deregulation of the autonomic nervous system. The longitudinal dimension of delayed onset muscle soreness, in the form of post orgasmic illness syndrome and the repeated bout effect, have cognitive and memory consequences, since the primary injury is learning and memory-related.

Sirtuins: Potential Therapeutic Targets for Defense against Oxidative Stress in Spinal Cord Injury

Spinal cord injury (SCI) is one of the most incapacitating neurological disorders. It involves complex pathological processes that include a primary injury and a secondary injury phase, or a delayed stage, which follows the primary injury and contributes to the aggravation of the SCI pathology. Oxidative stress, a key pathophysiological event after SCI, contributes to a cascade of inflammation, excitotoxicity, neuronal and glial apoptosis, and other processes during the secondary injury phase. In recent years, increasing evidence has demonstrated that sirtuins are protective toward the pathological process of SCI through a variety of antioxidant mechanisms. Notably, strategies that modulate the expression of sirtuins exert beneficial effects in cellular and animal models of SCI. Given the significance and novelty of sirtuins, we summarize the oxidative stress processes that occur in SCI and discuss the antioxidant effects of sirtuins in SCI. We also highlight the potential of targeting sirtuins for the treatment of SCI.

TITLE Role of closed loop INTELLIVENT -ASV mode ventilation in Head Injury patients as compared to conventional ventilation modes. (Preprint)

BACKGROUND INTRODUCTION Traumatic brain injury (TBI) is common in all hospitals over Pakistan and it is associated with significant morbidity and mortality. It presents with varying levels of severity. Intensive monitoring and early suspicion of complications make it a mandatory sensitive issue. Moderate to severe head injuries require elective and/or emergency mechanical ventilation at an early stage. Hence, choosing an appropriate mode of ventilation and providing optimum ventilation can help prevent secondary brain injury, which result from ischemic and hypoxic changes in the brain due to injury. Mortality and morbidity of head injury coincides directly with the severity of the injury. Moreover, superimposed secondary brain Injury on a primary injury increases the severity of the injury, decreases the time of the therapeutic window and hence increases the morbidity and mortality of the TBI. An appropriate mechanical ventilation therapy at an early stage of a head injury can help preserve the primary injury, decrease the progression to a secondary Injury, prevent a cascade reaction where an Injury imposes further decompression of the brain and hence by decreasing morbidity can help decrease mortality. OBJECTIVE To determine outcomes of head injury patients ventilated with closed loop IntelliVent-ASV mode as compared to conventional SIMV ventilation mode based on maintenance of PEtCO2. METHODS STYDY DESIGN Randomized controlled trial. SETTING POF Hospital, Wah Cantt STUDY PERIOD Six months after approval of synopsis SAMPLING TECHNIQUE Non probability consecutive sampling SAMPLE SIZE A total of 100 patients with head injury fulfilling the inclusion criteria were selected and randomly allocated into two groups containing 50(n) each. RESULTS Data was analysed using SPSS Version 17. EtCO2 was measured continuously via mainstream EtCO2 . The IntelliVent ASV patients were randomally assigned group A while SIMV patients were assigned group B. Mean GCS score among both groups was 6.18+1.27 and 6.22+1.20 .Average EtCO2 reading among both groups was 34.58+2.01 and 35.58+2.12 respectively. Mean no. of manual adjustments among both groups was 7.50+3.40 and 6.25+0.88 respectively. After performing statistical analysis P value was <0.000 which was statistically significant. CONCLUSIONS Closed loop automated mode in head injury patients secure better outcomes than conventional mode in terms of decreased morbidity. Although the study needs more number of patients and time to determine the efficacy of one mode over another. CLINICALTRIAL ISRCTN10127188 https://doi.org/10.1186/ISRCTN10127188

Endothelial glycocalyx in traumatic brain injury associated coagulopathy: potential mechanisms and impact

Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide; more than 10 million people are hospitalized for TBI every year around the globe. While the primary injury remains unavoidable and not accessible to treatment, the secondary injury which includes oxidative stress, inflammation, excitotoxicity, but also complicating coagulation abnormalities, is potentially avoidable and profoundly affects the therapeutic process and prognosis of TBI patients. The endothelial glycocalyx, the first line of defense against endothelial injury, plays a vital role in maintaining the delicate balance between blood coagulation and anticoagulation. However, this component is highly vulnerable to damage and also difficult to examine. Recent advances in analytical techniques have enabled biochemical, visual, and computational investigation of this vascular component. In this review, we summarize the current knowledge on (i) structure and function of the endothelial glycocalyx, (ii) its potential role in the development of TBI associated coagulopathy, and (iii) the options available at present for detecting and protecting the endothelial glycocalyx.

Role of 5-HT in Cerebral Edema after Traumatic Brain Injury

The pathogenesis of edema after traumatic brain injury is complex including the destruction of micro-vessels and alterations in microcirculation around the primary injury and leakage of plasma constituents into the tissue, due to permeability changes of the vessel walls. Many functional molecules like histamine, serotonin, arachidonic acid, prostaglandins and thromboxane have been shown to induce blood–brain barrier (BBB) disruption or cell swelling. It is believed that released 5-HT binds to 5-HT2 receptors stimulating cAMP and prostaglandins in vessels that cause more vesicular transport in endothelial cells leading to serum component’s extravasation. The additional amount of serotonin into the tissue due to injury maintains the state of increased vascular permeability that ultimately causes edema. Serotonin is clearly involved in early cytotoxic edema after TBI. Reduction of serotonin in the nervous tissue reduces swelling and the milder cell changes in the brain or spinal cord of traumatized rats. Inhibition of serotonin synthesis before closed head injury (CHI) in rat models or administration of serotonin antiserum after injury attenuates BBB disruption and brain edema volume swelling, and brain pathology. Maintaining low serotonin levels immediately after injury may show neuroprotection and combat various secondary outcomes that occur after traumatic brain injury.