Clinical Phenomenon Research Articles

An osteoarthritis subtype characterized by synovial lipid metabolism disorder and fibroblast-like synoviocyte dysfunction.

BackgroundThe heterogeneity of osteoarthritis (OA) significantly limits the effectiveness of pharmacological treatments in an unselected patient population. In this context, the identification of OA subtypes is meaningful for the development of therapies that target specific types of OA pathogenesis.MethodsExpression array profiles of 70 OA and 36 control synovial samples were extracted from the GEO database. Unsupervised consensus clustering was performed based on the most variable genes to identify OA subclusters. Next, Joint samples from OA patients were obtained. We divided the OA patient into two subpopulations according to synovial ADCY7 levels. Synovium and cartilage samples from different OA subpopulations were evaluated. In addition, we established a high-fat diet (HFD)-induced rat OA model. We evaluated OA progression, lipid metabolism, synovitis and fibroblast-like synoviocytes (FLS) function in this HFD-induced OA model.Results70 OA patients were categorized into three distinct subclusters. We noted that one subcluster was characterized by synovial lipid metabolism disorder GO terms. We further identified the most noticeable KEGG pathway “Regulation of lipolysis in adipocytes” in this subcluster as well as the most significantly differentially expressed gene, ADCY7. We found that the ADCY7 high expressing group (32.6%) exhibited features of synovial inflammatory lipolysis epithelial-mesenchymal transition (EMT) tendency, as well as faster join space narrowing. The HFD induced OA-like degeneration in rat joints. We observed similar synovial inflammatory lipolysis and EMT in FLS, characterized by higher proliferative and invasive activity and elevated proinflammatory and procatabolic properties. ADCY7 was highly expressed in the synovium of the HFD-OA model rats and the inhibition of ADCY7 effectively attenuated these HFD-induced degenerative changes as well as synovial inflammatory lipolysis and FLS dysfunction. In HFD-FLSs, ADCY7 promoted the phosphorylation of PKA as well as its downstream lipid droplet-associated protein PLIN1 and hormone-sensitive lipase (HSL). The inhibition of PKA largely alleviated ADCY7-mediated HFD-FLS dysfunction.ConclusionsWe described a synovial EMT and lipid metabolism disorder in the pathogenesis of OA. This novel mechanism may represent a currently undefined OA subtype. ADCY7 is a potential molecular marker of this pathomechanism.The Translational potential of this articleUtilizing synovial samples from OA patients, we identified a subpopulation with high ADCY7 expression. This may represent a currently undefined OA subtype and explain the clinical phenomenon of more severe synovial inflammation in obese OA patients. In addition, we established an HFD-induced OA rat model and found an upregulation of ADCY7 in the synovium. We confirmed that the inhibition of ADCY7 could effectively attenuate HFD-induced degenerative changes as well as the inflammatory lipolysis and FLS dysfunction observed in the rat model. This suggests that ADCY7 and its downstream pathways are potential pharmacological targets for treating this lipid-metabolism-disorder-related OA mechanism.

Beyond the ‘normal’ worries: detection and treatment of perinatal anxiety and anxiety disorders

SUMMARYIn clinical psychiatry, it is common to see pregnant and postpartum patients who express excessive anxiety and concerns about pregnancy or childbearing. This implies the need to distinguish between symptoms that could be considered to be an expected reaction to the situation, the diagnosis of an anxiety disorder or the presence of pregnancy-related (pregnancy-specific) anxiety. The last presents as a specific clinical phenomenon, identified in the literature as concerns exclusively linked to the situation of pregnancy or childbirth. In this article I review key points in the differential diagnosis of perinatal anxiety and its impact on both the pregnancy and the baby, as well as aspects of detection and diagnosis. I also give a brief summary of possible management approaches and treatments.

The Outer Membrane Lipoprotein Tp0136 Stimulates Human Platelet Activation and Aggregation Through PAR1 to Enhance Gq/Gi Signaling.

BackgroundChancre self-healing, a typical clinical phenomenon of primary syphilis, is essentially wound healing. The first response to a wound is constriction of the injured blood vessels and activation of platelets to form a fibrin clot. However, the role of Treponema pallidum in platelet activation and clot formation remains unclear.ObjectivesWe aimed to elucidate the role of the outer membrane Treponema pallidum lipoprotein Tp0136 in human platelet activation and aggregation and explore the related mechanism.MethodsA series of experiments were performed to assess the effects of Tp0136 on human platelet activation and aggregation in vitro. The effect of Tp0136 on platelet receptors was studied by detecting PAR1 protein levels and studying related receptor sites. The involvement of the Gq/Gi signaling pathway downstream of PAR1 was explored.ResultsTp0136 significantly accelerated the formation of human platelet clots as well as platelet adhesion to and diffusion on fibrinogen to promote platelet aggregation. Tp0136 also potentiated P-selectin expression and PF4 release to promote platelet activation and downregulated PAR1 expression. The activation and aggregation induced by Tp0136 were reverted by the specific PAR1 antagonist RWJ56110 and the human PAR1 antibody. In addition, Tp0136 significantly enhanced Gq and Gi signaling activation, thereby triggering p38 phosphorylation and Akt-PI3K activation, increasing the release of intraplatelet Ca2+ and attenuating the release of cytosolic cAMP. Furthermore, the specific PAR1 antagonist RWJ56110 significantly suppressed Gq and Gi signaling activation.ConclusionsOur results showed that the Treponema pallidum Tp0136 protein stimulated human platelet activation and aggregation by downregulating PAR1 and triggered PAR1-dependent Gq and Gi pathway activation. These findings may contribute to our understanding of the self-healing of chancroid in early syphilis.

Dissociative Model in Patients With Resistant Schizophrenia.

BackgroundSchizophrenia is a severe mental illness in which, despite the growing number of antipsychotics from 30 to 50% of patients remain resistant to treatment. Many resistance factors have been identified. Dissociation as a clinical phenomenon is associated with a loss of integrity between memories and perceptions of reality. Dissociative symptoms have also been found in patients with schizophrenia of varying severity. The established dispersion of the degree of dissociation in patients with schizophrenia gave us reason to look for the connection between the degree of dissociation and resistance to therapy.MethodsThe type of study is correlation analysis. 106 patients with schizophrenia were evaluated. Of these, 45 with resistant schizophrenia and 60 with clinical remission. The Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scales were used to assess clinical symptoms. The assessment of dissociative symptoms was made with the scale for dissociative experiences (DES). Statistical methods were used to analyze the differences in results between the two groups of patients.ResultsPatients with resistant schizophrenia have a higher level of dissociation than patients in remission. This difference is significant and demonstrative with more than twice the level of dissociation in patients with resistant schizophrenia.The level of dissociation measured in patients with resistant schizophrenia is as high as the points on the DES in dissociative personality disorder.ConclusionPatients with resistant schizophrenia have a much higher level of dissociation than patients in clinical remission. The established difference between the two groups support to assume that resistance to the administered antipsychotics is associated with the presence of high dissociation in the group of resistant patients. These results give us explanation to think about therapeutic options outside the field of antipsychotic drugs as well as to consider different strategies earlier in the diagnostic process.

How laboratory studies of cigarette craving can inform the experimental alcohol craving literature.

Interest in alcohol and other drug craving has flourished over the past two decades, and evidence has accumulated showing that craving can be meaningfully linked to both drug use and relapse. Considerable human experimental alcohol craving research since 2000 has focused on craving as a clinical phenomenon. Self‐reported craving to drink typically has served as a catch‐all for the craving construct in these studies, whereas few studies have considered craving as a process (or hypothetical construct) that interacts with other phenomena to affect use. In contrast to alcohol, we believe that recently there has been more mechanistic work targeting cigarette craving–related processes. Here, we briefly present a narrative review of studies of acute alcohol craving in humans that have been conducted during the past two decades. We then specify important ways in which alcohol and tobacco differ (e.g., the role of withdrawal), and we note the unique challenges in inducing robust alcohol craving states in the laboratory. Finally, we offer recommendations for how the alcohol field might advance its conceptual understanding of craving by adopting ideas and methods drawn from the smoking research literature. Specifically, we suggest that researchers extend their studies to not only examine the link between alcohol craving and relapse but also to focus on why and, in some instances, how alcohol cravings matter clinically, and the circumstances under which craving especially matters. We propose research to investigate the shifts in alcohol‐related cognitive and affective processing that occur during alcohol craving states. Furthermore, we highlight the value of research examining the level of insight that individuals with varying levels of alcohol involvement possess about their own craving‐related processing shifts. We believe that laboratory studies can provide rich opportunities to examine conceptual questions about alcohol craving that are central to addiction.

Free Papers Compiled

BACKGROUNDThe association between testosterone and depression is extensively debated1. Testosterone being a neuro-active steroid hormone, is responsible for growth and development of male primary sexual organs2, musculoskeletal system and influencing mood and appetitive behaviour1. Several lines of research have examined the potential role of testosterone therapy in alleviating depressive symptoms1. Thus, considering hypo-testosteronism as a differential diagnosis of depressive disorders in males or testosterone supplementation in such cases as treatment for depression is important but not commonly practiced.CASE SERIESIn this case series, we describe two male patients with young onset depression, who did not respond to adequate trials of multiple antidepressants, were evaluated independently elsewhere by endocrinologist,and detected to have low levels of testosterone. The depressive symptoms improved with initiation of testosterone supplementation in both the cases.DISCUSSION & CONCLUSIONThis case series provides insight into this clinical phenomenon where low testosterone may be associated with depressive mood symptoms, thus testosterone supplementation being imperative in such cases. Testosterone causes increased serotonin release in the dorsal raphe nuclei and facilitates general and antidepressant-induced neuroplasticity in the hippocampal formation, which can be considered as central mechanisms of action against depression1. The beneficial role of testosterone use may thus be independent of hypogonal state as well.However, further studies are needed to ascertain the utility of initiating testosterone use in certain patient groups and develop guidelines to assess for hypo-testosteronism in young males with treatment resistant depression.Reference1. Walther A, Breidenstein J, Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men: a systematic review and meta-analysis. JAMA psychiatry. 2019 Jan 1;76(1):31-40.2. Ravan JP, Pattnaik JI, Nath S, Kumar S. Intervention Strategy for Amennorhoea, Galactorrhoea, osteopenia and Sexual dysfunction caused by Antipsychotic induced Hyperprolactinemia. In indian journal of psychiatry 2019 jan 1 (vol. 61, no. 9, pp. S443-s443). Wolters kluwer india pvt ltd, a-202, 2nd flr, qube, cts no 1498a-2 village marol, andheri east, mumbai, 400059, india: wolters kluwer medknow publications.

Leser trelat znak u dijagnozi okultnih neoplazmi-prikaz slučaja

Leser-Trélat (LT) sign (syndrome) is a rare, distinctive clinical phenomenon that is manifested by a sudden, eruptive, appearance of multiple itchy seborrheic keratoses (SK) that sometimes coincide with occult malignancy. A 73-year-old patient came for examination of numerous, large seborrheic keratoses (SK) on the skin. According to the patient's statement, SK did not occur suddenly and "eruptively". Nevertheless, ultrasound and endoscopic evaluation were suggested to the patient to exclude the Leser-Trélat phenomenon. The patient was then diagnosed with an occult, asymptomatic rectal neoplasm. The occurrence of numerous seborrheic keratoses (especially if they are "eruptive", large and bizarre in shape), should raise suspicion of LT phenomenon, or internal malignancy in the patient, and result in relevant diagnostic procedures to detect possible latent malignancy. It would be wise for the doctors of all disciplines to be acquainted with the existence of the LT sign (syndrome) and possible clinical implications of it.

Gender dysphoria in adults

Gender dysphoria (GD) is a condition where one feels distressed about one's assigned gender at birth. The construct has undergone successive revisions in understanding and terminology in contemporary classificatory systems. Currently, the terms “GD” and “gender incongruence” are used in the Diagnostic and Statistical Manual of Mental Disorders-5 and International Classification of Diseases-11, respectively. However, there continues to be a lack of clarity on terminologies used in describing related concepts. Sex is an inflexible categorical concept, whereas gender is a social construct. It is vital to understand and distinguish between sexual orientation and gender identity. Clarity in understanding and usage of these and other related terms in the field is central to addressing the issue of stigma faced by the members of the lesbian, gay, bisexual, transgender, queer, intersex, asexual+ (LGBTQIA+) community, an umbrella term used to denote individuals with nonconformative gender identity and orientation. Several clinical and ethical issues exist with diagnosing and managing GD such as optimal treatment of minors, fertility after gender affirming treatments, and dissatisfaction following gender reassignment. To clarify these issues and facilitate access to care for LGBTQIA+ individuals, the GD category has been retained in the classificatory systems despite activists calling for dropping the term from diagnostic manuals to minimize associated stigma. Other controversies in the area include inclusion of childhood GD diagnosis on the grounds of uncertainty of longitudinal trajectory of the clinical phenomenon and use of nonevidence-based, potentially harmful, treatments such as “conversion therapies.” There is a need to sensitize clinicians about these issues and mainstream them in the assessment and management of GD. Such an approach would aid development of culturally sensitive and evidence-based treatments for gender variance.

Unusual presentation of a patent ductus arteriosus: A case report

A 48 years old patient, with no medical history was referred to the cardiovascular surgeon of our department for a right medio-ventricular resection diagnosed after 2 episodes of syncope. The transthoracic echocardiography revealed a severe RV hypertrophy with aspect of sub-pulmonary stenosis. An invasive hemodynamic assessment was performed and concluded to a severe Pulmonary arterial hypertension. During the invasive right cardiac exploration, the catheter run easily into an unknown large patent ductus arteriosus (PDA). PDA in adults is an extremely rare clinical phenomenon since it is usually discovered and treated during childhood. However, physicians need to be aware of potential situations, signs and symptoms that might suggest a previously undiagnosed PDA.

Hypoxemia: from pathophysiology to diagnosis

Hypoxemia is defined as a decreased oxygen partial pressure in arterial blood. This frequent clinical phenomenon can lead to tissue hypoxia and requires a prompt diagnostic approach to guide its management. Five pathophysiological mechanisms should be assessed in the presence of hypoxemia: alveolar hypoventilation, ventilation/perfusion mismatches, diffusion disorders, true shunts and a decrease in the partial pressure of inspired oxygen. In this article, we synthesize the main etiologies of hypoxemia based on respiratory pathophysiology and suggest a diagnostic approach for its evaluation.

Assessment of open surgical and endovascular management of true hepatic artery aneurysms over 20 years highlights increased rupture risk in females

BackgroundTrue hepatic artery aneurysms (HAAs) are rare but have been associated with a significant risk of rupture and associated mortality. The 2020 release of HAA-specific clinical practice guidelines represented an important step toward management standardization. However, it remains essential to build on the body of evidence to further refine these recommendations. MethodsThe HAA management and outcomes from a single academic center during a 20-year period were retrospectively reviewed. We identified 72 patients from the institutional radiology database (November 24, 1999 to 2019). Pseudoaneurysms were excluded, and 48 patients were found to have had true HAAs. Forty-three HAA patients had sufficient medical records for inclusion in the analysis. ResultsOf the 43 patients with HAA included, 65% were male. The mean age was 63 years (range, 22-89 years). Of the HAAs, 72% presented asymptomatically, 16% had ruptured, and 12% were symptomatic at presentation. Most HAAs were of atherosclerotic origin (74%). In addition, 16% of the patients had other visceral aneurysms and 12% had nonvisceral aneurysms on presentation. The mean HAA size overall was 3.3 cm (range, 0.8-10.8 cm), with most being solitary (72%) and involving the common hepatic artery (65%). Rupture was more common in females (40%) and those with vasculitis (67%), with females representing 86% of all patients with rupture. The mean size at intervention was 4.8 cm (21 patients [49%]). Ten patients (23%) had undergone open surgical repair (seven elective and three emergent because of rupture). Eleven patients (26%) had undergone endovascular intervention (64% elective and 36% emergent). Nonoperative management was selected for 22 patients (51%). These patients had a mean HAA diameter of 2.1 cm, and 59% had a life-limiting illness. Of the 18 patients who had been initially monitored for a mean of 3.9 ± 4.1 years, 3 had undergone elective repair and 2 had minimal growth. None of these patients had a subsequently documented rupture. ConclusionsTrue HAAs are a rare but important clinical phenomenon, with 16% of patients presenting with rupture in this study. Endovascular intervention is a promising alternative to open surgical repair, with no 30-day mortality, and is suitable for ruptured HAAs. Importantly, for the first time, our findings have demonstrated an increased risk of rupture for females, highlighting the need for additional data and ultimately, sex-specific guidelines.

Recurrent Implantation Failure-Is It the Egg or the Chicken?

Recurrent implantation failure (RIF) is an undefined, quite often, clinical phenomenon that can result from the repeated failure of embryo transfers to obtain a viable pregnancy. Careful clinical evaluation prior to assisted reproduction can uncover various treatable causes, including endocrine dysfunction, fibroid(s), polyp(s), adhesions, uterine malformations. Despite the fact that it is often encountered and has a critical role in Assisted Reproductive Technique (ART) and human reproduction, RIF’s do not yet have an agreed-on definition, and its etiologic factors have not been entirely determined. ART is a complex treatment with a variable percentage of success among patients and care providers. ART depends on several factors that are not always known and probably not always the same. When confronted with repeated ART failure, medical care providers should try to determine whether the cause is an embryo or endometrium related. One of the most common causes of pregnancy failure is aneuploidy. Therefore, it is likely that this represents a common cause of RIF. Other RIF potential causes include immune and endometrial factors; however, with a very poorly defined role. Recent data indicate that the possible endometrial causes of RIF are very rare, thereby throwing into doubt all endometrial receptivity assays. All recent reports indicate that the true origin of RIF is probably due to the “egg”.

Sports Injury Modeling of the Anterior Cruciate Ligament Based on the Intelligent Finite Element Algorithm.

In order to solve the problem of sports injury modeling of the anterior cruciate ligament, a method based on the intelligent finite element algorithm is proposed. Considering the transverse isotropy of the ligament, this paper constructs a 3D finite element model of the knee joint based on medical image data. The same ligament constitutive equation was used to fit the parameters of stress-strain mechanical experimental curves of three different anterior cruciate ligaments, and the effects of different anterior cruciate ligament mechanical parameters on kinematics and biomechanical properties of the knee joint were compared. The experimental results show that, in models 1, 2, and 3, the maximum stress values appear in the posterolateral of the femoral attachment area of the ligament, which are 16.24 MPa, 16.36 MPa, and 22.05 MPa, respectively. However, the stress values at the tibial attachment area are 9.80, 13.8, and 13.93 MPa, respectively, and the stress values at the anterolateral part of the middle ligament are 6.36, 11.89, and 12.26 MPa, respectively, which are all smaller than those at the femoral attachment area, which also quantitatively explains the clinical phenomenon that ACL fracture often occurs in the femoral attachment area in practice. Thus, the three-dimensional finite element model of the knee joint highly simulates the structure and material properties of the knee joint. This method proves that the intelligent finite element algorithm can effectively solve the modeling problem of sports injury of the anterior cruciate ligament.

Protective effects of progesterone on pulmonary artery smooth muscle cells stimulated with Interleukin 6 via blocking the shuttling and transcriptional function of STAT3

BackgroundSex hormone paradox is a crucial but unresolved issue in the field of pulmonary artery hypertension (PAH), and is thought to be related to different pathogenic factors. Inflammation is one of pathological mechanisms of PAH development. However, effects of sex hormones on the pulmonary vasculature under the condition of inflammation are still elusive. MethodsInterleukin-6 (IL-6) was used as a representative inflammatory stimulator. Effects of 17β-estradiol or progesterone on human pulmonary artery smooth muscle cells (PASMCs) were measured under the condition of IL-6. Cell functions of proliferation and migration were measured by Alarmar Blue, EdU assay, wound-healing assay and transwell chambers. We explored further mechanisms using western blot, immunofluorescence, co-immunoprecipitation, qPCR and chromatin immunoprecipitation. ResultsOur results revealed that IL-6 promoted the proliferation of PASMCs, but progesterone could reverse the adverse effect of IL-6. The protective effect was dependent on progesterone receptor (PGR). By interacting with signal transducer and activator of transcription 3 (STAT3), activated PGR could reduce the IL-6-induced nuclear translocation of STAT3 and prevent STAT3-chromatin binding in PASMCs, leading to the decreased transcription of downstream CCND1 and BCL2. Alternatively, progesterone slightly decreased the phosphorylation of pro-proliferative Erk1/2 and Akt kinases and upregulated the anti-proliferative pSmad1-Id1/2 axis in IL-6-incubated PASMCs. ConclusionsProgesterone played a protective role on PASMCs in the context of IL-6, by blocking the functions of STAT3. Our findings might assist in explaining the clinical phenomenon of better prognosis for women with PAH.

Transdisciplinary Clinical Practice between Physiotherapists and Traumatologists in Orthopaedic Medicine

Introduction: The transdisciplinary scope is conceived as an emerging practice and corpus of knowledge since it comes from the interactions between different disciplines. Transdisciplinarity emerges to solve in a more efficient way health problems of humanity that overcome the traditional biomedical interdisciplinary attention model. In this article, the transdisciplinary physiotherapist is exposed as the beginning of an authentic dialogue between the physiotherapist and the traumatologist in the care of the orthopedic patient that includes all treatment phases of integral rehabilitation, as well as its factors to consider the possible advantages and dares that this scope may present to the health services.
 Objective: This paper aims to propose to the scientific community the context of transdisciplinary clinical practice between traumatologists and physical therapists.
 Methods: It is performed a grounded theory approach to develop a thesis based on our observations and a reflection of literature that intends to explain transdisciplinary clinical practice phenomenon between traumatologists and physical therapists and pose the potential outcomes of this interactions and its implications.
 Conclusion: Exist theoretical and practical background to support the clinical practice of transdisciplinary care in Orthopedic and Physical Therapy attention; which make possible professionals to develop transdisciplinary clinical skills, and team shared decision making. Transdisciplinary clinical practice, as with any educational process, should ideally foster specific shared competencies in healthcare professionals, including teamwork, leadership, consensus building, the ability to identify and achieve common patient care goals and variable shared practical skills that may even include other specialization areas.

The use of transdermal therapeutic systems for chemical pleurodesis in a patient with prolonged air leakage after lung resection for cancer

This clinical observation demonstrates a method of a motivated use of a transdermal therapeutic system (TTS) based on fentanyl for chemical pleurodesis in a patient with prolonged air leakage after lung resection for cancer. The most common complication after elective lung resections is an alveolar-pleural fistula or prolonged air leakage. This clinical phenomenon occurs as a result of communication between the alveoli of the lung parenchyma distal to the segmental bronchus and the pleural cavity. In most cases, air leakage through the drains is eliminated spontaneously, but the frequency of prolonged pneumostasis absence in the postoperative period can reach 25 %, which has a negative effect on the outcomes of surgical interventions due to the development of pneumonia and empyema. Long-term drainage of the pleural cavity does not always end with aerostasis and requires repeated invasive interventions. One of the ways to achieve the tightness of the lung tissue involves various methods of chemical pleurodesis, which is a surgical manipulation – the introduction of a sclerosing chemical substance into the pleural cavity by spraying medical talc through a trocar or a injecting tetracycline solution into the pleural drains. The chemical causes aseptic inflammation and adhesions between the visceral and parietal pleura, followed by obliteration of the pleural cavity. The sclerosant introduction is accompanied by severe pain that can provoke respiratory and/or hemodynamic deficits, up to apnea and life-threatening heart rhythm disturbances. Pain relief during chemical pleurodesis is obviously an important factor in the prevention of a number of complications in patients undergoing surgery for lung cancer. Bolus intravenous injections of narcotic analgesics lead to an analgesic effect, but a short-term one due to the absence of a depot in the body and a sharp drop in the drug concentration in the blood serum. Unfortunately, this method of introducing narcotic drugs can cause various complications in weakened and elderly cancer patients, such as respiratory depression and cardiac arrest. The TTS action is characterized with continuous dosing and the creation of a constant concentration of the narcotic drug over a certain period of time. This method provides a multilevel and systematic approach to pain relief, reduces toxicity and minimizes the inhibition of the central mechanisms of external respiration regulation without causing respiratory and cardiac disorders in patients who underwent lung resection.

Intertumoural Heterogeneity and Branch Evolution of Synchronous Multiple Primary Lung Adenocarcinomas by Next-Generation Sequencing Analysis.

ObjectivesMultiple primary lung cancers (MPLCs) are an increasingly well-known clinical phenomenon, but there is a lack of high-level evidence for their optimal clinical diagnosis and therapeutic approaches. Thus, we analysed genetic variation to determine the intertumoural heterogeneity and branch evolution of synchronous multiple primary lung adenocarcinomas.MethodsWe performed multiplex mutational sequencing on 93 synchronous multiple primary lung adenocarcinoma lesions from 42 patients who underwent surgical resection.ResultsThe high discordance rate of mutation was 92.9% (n=39) between tumours in individual patients. EGFR, TP53 and KRAS mutations were detected in 57 (61.3%), 19 (20.4%) and 11 (11.8%) of the 93 tumours, respectively. 16 cases of multiple primary lung adenocarcinomas simultaneously harboured EGFR mutations and TP53 mutations. Matching mutations between paired tumours were observed in 1 (2.4%) patient for P20. The genotypes were all EGFR L858R mutations, but the pathological type of P20T1 was lepidic predominant, and P20T2 was adenocarcinoma in situ. In the phylogenetic tree, genetic variations were divided into trunk, shared and branch subtypes. Branch mutations accounted for 91.09% of variations in sMPLA, while the ratio of trunk (4.95%) and shared (3.96%) variations was significantly lower.ConclusionsRemarkable intertumoural heterogeneity and frequent branch mutations were found in synchronous multiple primary lung adenocarcinomas.

Proximal junctional kyphosis in pediatric spinal deformity surgery: a systematic review and critical analysis.

Proximal junctional kyphosis (PJK) is a commonly encountered clinical and radiographic phenomenon after pediatric and adolescent spinal deformity surgery that may lead to post-operative deformity, pain, and dissatisfaction. Understanding the risk factors of PJK can be useful for pre-operative informed consent as well as to identify any potential preventative strategies. We performed a systematic review and critical analysis following the PRISMA statement in July 2019 by searching the PubMed, Scopus, and Embase databases, including all prior published studies. We included articles with data on PJK in patients with operative pediatric and adolescent scoliosis and those that detailed risk factors and/or preventative strategies for PJK. Levels of evidence were determined based on consensus. Findings were summarized and grades of recommendation were assigned by consensus. This study was registered in the PROSPERO database; 202,457. Six hundred and thirty five studies were identified. Thirty-seven studies met criteria for inclusion into the analysis. No studies including neuromuscular scoliosis met inclusion criteria. No findings had Grade A evidence. There were 4 findings found to contribute to PJK with Grade B evidence in EOS: higher number of distractions, disruption of posterior elements, greater sagittal plane correction. There was no difference in incidence noted between etiology of the curvature. Five findings with Grade B evidence were found to contribute to PJK in AIS populations: higher pre-operative thoracic kyphosis, higher pre-operative lumbar lordosis, longer fusion constructs, greater sagittal plane correction, and posterior versus anterior fusion constructs. Greater sagittal plane correction has Grade B evidence as a risk factor for PJK in both EOS and AIS populations. In EOS patients, an increased number of distractions and posterior element disruption are Grade B risk factors. In AIS patients, longer fusion constructs, higher pre-operative thoracic kyphosis and lumbar lordosis, and posterior (as opposed to anterior) constructs also contributed to PJK with Grade B evidence. These findings can guide informed consent and surgical management, and provide the foundation for future studies.

Returned traveller presenting with anaemia: clinical challenge of post-artesunate delayed haemolysis.

Although malaria is one of the differential diagnoses among travelers to endemic area, delayed hemolysis following malaria treatment with artemisinin-derivative drugs during travel should be aware. We highlight the clinical perspective for clinicians to consider this clinical phenomenon to detect any delayed hemolytic event early and prevent potentially serious consequences.

Delirium-The Effect of Children Anesthesiology after Surgery

Delirium of anesthesiology is a clinical phenomenon widespread in children. Although the pathophysiology is still uncertain, some factors seem to be involved, such as rapid awakening in an unknown environment, agitation during anesthetic induction, preoperative anxiety, environmental disorders, pre-anesthetic medication, and inhalational anesthetics. There remain unanswered questions and implications related to the emergence of delirium in children. Although we know that there are some predisposing factors to emergence delirium, we still cannot accurately identify those at most significant risk. Emergent delirium should be considered a ‘vital sign,’ which should be followed and documented in every child in the postanaesthesia recovery period. What should adopt standardized screening tools for pediatric emergence delirium (ED)