In-vivo neuronal dysfunction by Aß and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer's disease.

The molecular mechanisms underlying neuronal dysfunction in Alzheimer's disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aß) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aß- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aß and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant's real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aß-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aß and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aß and tau's synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aß-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.

Patient reported outcomes of emergency general surgery procedures.

BACKGROUND: Emergency general surgery (EGS) involves care of a patient's often previously unknown disease in the setting of an unplanned interaction with the healthcare system. This leads to challenges collecting and interpreting patient reported outcome measures (PROMs). METHODS: We performed a qualitative and mixed methods study using semi-structured interviews during the index hospitalization and at 6-12 months to capture peri-operative patient experiences. We compared interview findings to clinical characteristics. RESULTS: Among 30 patients, two-thirds reported feeling no choice but to pursue emergency surgery with many reporting exclusion from decision-making. Females reported these themes more commonly. Patients with minor complications less frequently reported trust in their team and discussed communication issues and delays in care (all p â€‹< â€‹0.05). Patients with major complications more frequently reported confidence in their team and gratefulness, but also communication limitations (all p â€‹< â€‹0.05). Patients not admitted to the ICU more frequently discussed good communication and expeditious treatment. CONCLUSIONS: PROMs developed for EGS patients should consider patient outcomes and reflections that they felt excluded from decision-making. Severity of complications may also differentially impact PROMs.

Tailoring parenting styles and family-based interventions cross-culturally as an effective prevention strategy for youth substance use: a scoping review.

Background: The challenge of substance use among youth continues to be a highly concerning public health issue across the globe. The notion that parenting lifestyles and family-based intervention can help in the prevention of adolescent substance use have received robust attention from policy makers, researchers' clinicians and general public, nonetheless, there is scarcity of high quality evidence to support these concepts. Objective: To review available literature which assessed the effects of parenting styles and family-based interventions on the prevention of adolescent substance use. Methods: A scoping review of literature to identify studies published in English between 2012 and 2022 was conducted searching Scopus, MEDLINE, PsychInfo, and CINAHL databases focused on effects of parenting styles and family-based interventions in the prevention of adolescent substance use.Keywords of family-based intervention strategies and possible outcomes of parenting styles on youth substance use were coded from the results, discussion, or conclusion. Strategies were inductively categorized into themes according to the focus of the strategy. Results: A total of 47 studies, published between 2012 and 2022 in English language included. Narrative synthesis illustrated that parental involvement, restriction of mature-rated content, parental monitoring, authoritative parenting styles, and parental support and knowledge can help in the prevention of adolescent substance use. On the contrary, poor parent-child bonding, overprotection, permissive parenting, parental frustrations, authoritarian and harsh parenting styles promoted adolescent substance use disorders. Proximal risk factors like peer influence, previous use of other substances, and risky behaviours had more effect than just parenting styles. Culturally tailored family-based intervention strategies such as "Preventive Parenting", "Parent Training", and "Parent Involvement", with focus on "Technology Assisted Intervention", particularly "SMART "(Substance Misuse among Adolescents in Residential Treatment) are found as effective family-based intervention strategies to mitigate substance use in youth. Conclusion: Culturally tailored family-based behavioural strategies psychosocial intervention strategies can be considered of the most effective strategies to prevent substance use disorders in youth.

A Case of Saphenous Vein Graft Aneurysm Treated With Percutaneous Coiling.

In adults, coronary artery bypass grafting (CABG) is a commonly performed surgery. Oftentimes, saphenous veins from the lower extremity are used as the graft vessels. A rare complication of this procedure is the formation of saphenous vein graft (SVG) aneurysms. We present the case of a 63-year-old male who presented to a referring emergency department with left-sided chest pain after falling off a ladder. The patient's initial chest X-ray revealed a suprahilar mass that was suspicious for being an aneurysm. A computerized tomography coronary angiogram indicated a large aneurysm. The patient was transferred to our facility for specialist evaluation. The patient's history was positive for two CABG procedures and a sternal wound infection, so a repeat sternotomy was not advisable. The SVG aneurysm was treated with percutaneous coiling. The patient tolerated the procedure well and was discharged home the next day.

The Use of Abatacept for the Treatment of Felty Syndrome in Rheumatoid Arthritis.

Felty syndrome is characterized by a triad of rheumatoid arthritis, neutropenia, and splenomegaly that typically occurs in patients with seropositive rheumatoid arthritis. We report a case of an 81-year-old man with a 22-year history of rheumatoid arthritis who developed pancytopenia and neutropenia for one month. An abdominal ultrasound revealed splenomegaly. A bone marrow biopsy excluded large granular lymphocytic leukemia, thus Felty Syndrome was diagnosed. He was treated with a maximum tolerated dose of methotrexate (15 mg once a week) for two months with no improvement in absolute neutrophil count. The patient was given abatacept 1000 mg intravenously every four weeks with improvement in hemoglobin, leukocyte, and platelet counts and absolute neutrophil counts from 0.2 to 2.4 K/µl.

Pre-transarterial Radioembolization of Tumoral Arteriovenous Fistula Associated With Recanalized Umbilical Vein Shunt in a Case of Hepatocellular Carcinoma With Hepatic Vein and Inferior Vena Cava Invasion.

Hepatocellular carcinoma (HCC) is the most common liver cancer and has a propensity to develop arteriovenous fistulas with the surrounding vasculature, making targeted intravascular treatment more difficult. HCC can oftentimes be accompanied by portal hypertension and liver cirrhosis, which can, in turn, cause recanalization of the umbilical vein. In rare circumstances, arteriovenous fistula formation and shunting into the recanalized and enlarged umbilical vein can occur. In the following presented case of HCC, an arteriovenous shunt between the anterior division of the right hepatic artery and a recanalized umbilical vein is demonstrated. Subsequent successful endovascular coil embolization of the fistula was performed to avoid shunting and non-target embolization of the radiation particles in the umbilical vein territory. Post-embolization angiogram with DynaCT and lack of Tc-99m macroaggregated albumin deposition in the umbilical vein distribution confirmed the resolution of the shunt. The patient then received targeted Y-90 transarterial radioembolization locoregional therapy in combination with systemic therapy.

Correction: Pretreatment Embolization of Tumoral Arteriovenous Fistula Associated With Recanalized Umbilical Vein Shunt in a Case of Hepatocellular Carcinoma With Hepatic Vein and Inferior Vena Cava Invasion.

[This corrects the article DOI: 10.7759/cureus.44784.].

Functional Outcome Of Bristow-Latarjet Procedure In Post-Traumatic Recurrent Anterior Shoulder Instability.

BACKGROUND: Due to its lack of bony support, the shoulder joint has the broadest range of motion out of all the joints in the body. Instead, one of the joints that dislocate most frequently is the shoulder joint. Multiple pathologic abnormalities, including the traumatic separation of the anterior-inferior capsule-labral complex from the glenoid rim, are caused by repeated anterior glenohumeral dislocation. The objective of the study is to ascertain the Bristow-LATARJET procedure's efficacy in situations of recurrent post-traumatic anterior shoulder instability. METHODS: From 31 January 2020 to 31 July 2020, a descriptive case series was undertaken in the orthopaedic surgery department of the Lahore General Hospital. For this study, 71 patients who met the inclusion and exclusion criteria were recruited, and all interventions were conducted while the patients were lying in a beach chair while under general anaesthesia. The Delto-pectoral incision surgical technique was applied. For 12 weeks, all patients underwent clinical follow-up, and the results were documented. RESULTS: There were 50(70.4%) males and 21(29.6%) females in this study & the mean age of the patients were 34.64±10.73. There were 37(52.1%) patients among them the outcome of treatment (Rowe Scale at 12th week) was excellent, among 21(29.6%) it was good, among 8(11.3%) it was fair and among 5 (7.0%) it was poor. There was a significant association between the outcome of treatment (Rowe scale at 12th week) and age groups (p-value: 0.000). CONCLUSIONS: The Bristow-LATARJET procedure is deemed to be a very productive, safe, and problem-free procedure for curing post-traumatic reoccurring traumatic anterior shoulder instability.

Spontaneous Regression of Metastatic Lesions of Adenocarcinoma of the Gastro-Esophageal Junction.

Spontaneous regression of cancer is a rarely recognized entity in modern medicine. Historically, this was recognized and hypothesized that an infection causes immune activation, indirectly stimulating the body to destroy tumor cells. Similarly, immune-oncology has now become a major modality in the treatment of solid and some liquid malignancies. However, now with improved therapeutic modalities in the oncology world, one does not get to appreciate our own immune system's ability to fight cancer. We present a patient who had spontaneous regression of metastatic adenocarcinoma of the gastroesophageal junction (GEJ). The patient is a 58-year-old female who had presented with early satiety and dysphagia for which she underwent esophagogastroduodenoscopy which showed an esophageal mass and endoscopic ultrasounds (EUSs) confirmed adenocarcinoma of the GEJ with metastasis to the regional lymph nodes and left supraclavicular lymph nodes. The patient had refused to undergo any surgical, medical oncological, or holistic treatments. Interim disease monitoring positron emission tomography-computed tomography (PET-CT) showed resolution of the metastatic sites of gastroesophageal cancer with clinical improvement of her symptoms. She continues to have this distant regression of metastatic gastroesophageal cancer six months after the initial diagnosis. In literature, spontaneous cancer regression has been reported in melanoma, renal cell carcinoma, and basal cell carcinoma. To our knowledge, this is the first case reported of spontaneous regression of metastatic lesions involving adenocarcinoma of the GEJ with no medical or surgical intervention.

Mackay Heart Failure Study: Examining the Root Causes, Compliance With Guideline-Based Therapy and Prognosis.

INTRODUCTION: Heart failure patients have poor outcomes comparable to some malignancies; however, the modern guideline directed medical therapy (GDMT) has improved its outcomes. The clinical characteristics and prescribers' compliance with GDMT for heart failure patients have not been studied in the Mackay region. METHODS: A retrospective cohort study of 115 consecutive adult heart failure patients was conducted at our institution. RESULTS: The study cohort consisted of 80% (n=92) males. Ischaemia was the leading cause accounting for 54% (n=62) of the cohort, followed by idiopathic cardiomyopathy at 32% (n=37). Drug-induced and Takotsubo cardiomyopathies were responsible for 11% and 1% respectively. Two (2) patients (2%) had valvular heart disease. Hypertension was present in 57% while diabetes and atrial fibrillation were present in 32% and 43% of patients. Fifty-nine per cent (59%) had a smoking history. All, except four patients, had reduced left ventricular ejection fraction (LVEF <50%) at diagnosis. Among patients with coronary ischaemia, 37% and 31% were revascularised with percutaneous coronary interventions and bypass graft surgeries, respectively. Renin-angiotensin-aldosterone system inhibitors and beta blockers were prescribed in 94% and 95% of the patients, respectively. Mineralocorticoid inhibitors were used in 25% while ivabradine was given to 8% of patients. Nine per cent (9%) of patients received cardiac resynchronisation therapy. Most patients had improvement in functional class and LVEF during follow-up. There were very few mortalities at 3% (n=3) at the median follow-up of 403 (IQR 239-896) days. CONCLUSION: Our study has shed light on heart failure epidemiology in the Mackay region. We found excellent compliance with GDMT and good prognosis for most patients in terms of both symptom and survival.

Malignant mesothelioma presenting as recurrent hydro-pneumothorax: An atypical case presentation and literature review.

Malignant Pleural Mesothelioma (MPM) is a rare pleural malignancy, with a vague presentation complicated by a decades-long latency period between environmental exposure and clinical manifestations. Spontaneous hydro-pneumothorax is a rare presentation of MPM, most often requiring invasive tissue biopsy to confirm the etiologic diagnosis. We present the case of 79-year-old male smoker with no documented history of asbestos exposure, who was found to have MPM after presenting with dyspnea and subsequently found to have recurrent hydro-pneumothorax. On Literature review of the limited documented cases of MPM with hydro-pneumothorax, we found an exclusively male population with a significant smoking history, a marked right sided pathology predominance, and a generally poor prognosis. While this corresponds with the examined case, and suggests that the presence of hydro-pneumothorax implies a high-grade tumor and significant tissue invasion, and therefore poor prognosis similar to that of stage 4 disease, it differs from more generalized case reviews of MPM, most importantly in their anatomical descriptions, prognostic indicators, and epidemiologic tendencies.

Distraction osteogenesis for correction of post ankylosis mandibular deformities.

Temporomandibular joint ankylosis, a debilitating disease mainly affecting children, is characterized by progressive restriction of mouth opening and maxilla-mandibular developmental deformities. Craniofacial distraction osteogenesis has been developed as a standard surgical strategy for rectification of craniofacial deformities. The purpose of this study was to assess mono-planar distraction devices for the correction of various mandibular asymmetries in patients with unilateral temporomandibular joint ankylosis who developed restricted mouth opening and mandibular retrognathia. All patients were treated using one-stage distraction osteogenesis followed by temporalis fascia interpositional arthroplasty under general anesthesia. A significant increase in mandibular ramus and base length was observed. Although an increase in anterior lower facial height was observed, it was not significant statistically. A decrease in posterior lower facial height and corpus was observed. Oblique distraction with angular osteotomy allowed lengthening of both the ramus and corpus, yielding satisfactory results and hence eliminating the need of secondary surgery. In conclusion, univector internal distractors are effective for correction of multi-planar mandibular deficiencies by optimizing its placement through meticulous planning.

Guidance and practice on frequency of HIV and sexually transmitted infection testing in men who have sex with men - what is the European situation?

Men who have sex with men (MSM) are at particular risk for HIV/sexually transmitted infections (STI). To investigate the European guidance used for MSM STI and HIV screening, risk level profiling and how this translated to practice, we conducted a questionnaire survey of leading physicians in the European branch of the International Union against Sexually Transmitted Infections (IUSTI). We identified that most European countries have limited guidance on screening intervals for MSM. Where risk profiling is advised, it is often left to clinicians to weight different behaviours and decide on screening frequency. Our results suggest that European MSM STI and HIV testing guidelines be developed with clear and specific recommendations around screening intervals and risk profiling. These guidelines will be particularly helpful due to rapidly evolving models of sexual healthcare, and the emergence of new providers who may benefit from guidelines that require less interpretation.

Bronchoscopic lung volume reduction.

The management of obstructive lung disease, particularly emphysematous lung disease, is aggressively being pursued. The patient populations that will experience the greatest benefit with lung volume reduction are those that are the worst candidates for surgical intervention. Identifying a bronchoscopic approach that has a true impact on this patient population will be a major accomplishment in the management of patients with chronic obstructive pulmonary disease. This article highlights the work currently ongoing in the area of bronchoscopic lung volume reduction. There are tools now clinically available in some locations throughout the world, but no standardized technique exists.

Safety of pacemakers and defibrillators in electromagnetic navigation bronchoscopy.

BACKGROUND: Electromagnetic Navigation Bronchoscopy (ENB) (InReach iLogic system; superDimension Inc) is a relatively new discipline, with promising diagnostic and therapeutic applications in patients with lung lesions. Navigation is performed in a magnetic field and, therefore, has been considered relatively contraindicated in patients with pacemakers and automated implantable cardioverter-defibrillators (AICDs). Potential risks include altering the function and shutting off the device, device damage, lead displacement, and potential overheating. Over the past decade, there has been extensive literature about the safety of pacemakers in either the 1.5-T or 3-T magnetic fields used in current MRI scanners. Although the magnetic field used in ENB is significantly weaker, 0.0001 T or approximately equal to the earth's gravity, its safety in patients with pacemakers is yet to be elucidated. We present our initial experience with ENB in patients with cardiac implanted electrical devices. METHODS: Twenty-four procedures in 24 patients with lung lesions and permanent pacemakers were performed. A cardiac electrophysiologist and programmer were present during the procedure. At baseline, the pacers were interrogated, and ECG was recorded. Continuous cardiac monitoring was performed during the procedure, and at the end, the pacer settings and function were reinterrogated to check for any changes. RESULTS: The procedures were all successfully concluded. None of the patients suffered any arrhythmias or disruption to their pacemakers' function. CONCLUSION: ENB appears to be safe when performed in patients with pacemakers and AICDs. Larger multicenter studies are needed to prove the final safety in this patient population.

Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer.

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab) (Genetech, Inc. 2008). This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG) and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical) atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.

EUS for detection of the hepatocellular carcinoma: results of a prospective study.

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) and accurate determination of the number of lesions are critical in determining eligibility for liver transplantation or resection. Current diagnostic modalities (CT and magnetic resonance imaging [MRI]) often miss small lesions. OBJECTIVE: To compare the accuracy of the EUS with CT for the detection of primary tumors of the liver. DESIGN: Prospective single-center study. SETTING: Academic medical center. PATIENTS: Subjects at high risk of HCC (hepatitis B, hepatitis C, or alcoholic cirrhosis) were enrolled. INTERVENTIONS: US, CT, MRI, and EUS examinations of the liver were performed. Liver lesions identified during EUS underwent EUS-guided FNA (EUS-FNA). RESULTS: Seventeen patients were enrolled in the study. Nine of these patients had liver tumors (HCC, 8; cholangiocarcinoma, 1). EUS-FNA established a tissue diagnosis in 8 of the 9 cases. The diagnostic accuracy of US, CT, MRI, and EUS/EUS-FNA were 38%, 69%, 92%, and 94%, respectively. EUS detected a significantly higher number of nodular lesions than US (P = .03), CT (P = .002), and MRI (P = .04). For HCC lesions, a trend was observed in favor of EUS for the detection of more lesions than US (8 vs 2; P = .06) and CT (20 vs 8; P = .06). No complications were observed as a result of EUS-FNA. LIMITATIONS: Small sample size. CONCLUSIONS: EUS-FNA is a safe and accurate test for the diagnosis of HCC. EUS increases the accuracy of intrahepatic staging of the HCC by delineation of lesions, which are missed by CT and MRI. We recommend EUS for suspected HCC, particularly in cases that are being considered for liver transplantation.

Endoscopic ultrasound as a first test for diagnosis and staging of lung cancer: a prospective study.

RATIONALE: Multiple tests are required for the management of lung cancer. OBJECTIVES: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was evaluated as a single test for the diagnosis and staging (thoracic and extrathoracic) of lung cancer. METHODS: Consecutive subjects with computed tomography (CT) findings of a lung mass were enrolled for EUS and results were compared with those from CT and positron emission tomography scans. RESULTS: Of 113 subjects with lung cancer, EUS was performed as a first test (after CT scan) for diagnosis in 93 (82%) of them. EUS-FNA established tissue diagnosis in 70% of cases. EUS-FNA, CT, and positron emission tomography detected metastases to the mediastinal lymph nodes with accuracies of 93, 81, and 83%, respectively. EUS-FNA was significantly better than CT at detecting distant metastases (accuracies of 97 and 89%, respectively; p = 0.02). Metastases to lymph nodes at the celiac axis (CLNs) were observed in 11% of cases. The diagnostic yields of EUS-FNA and CT for detection of metastases to the CLNs were 100 and 50%, respectively (p < 0.05). EUS was able to detect small metastases (less than 1 cm) often missed by CT. Metastasis to the CLNs was a predictor of poor survival of subjects with non-small cell lung cancer, irrespective of the size of the CLNs. Of 44 cases with resectable tumor on CT scan, EUS-FNA avoided thoracotomy in 14% of cases. CONCLUSIONS: EUS-FNA as a first test (after CT) has high diagnostic yield and accuracy for detecting lung cancer metastases to the mediastinum and distant sites. Metastasis to the CLNs is associated with poor prognosis. EUS-FNA is able to detect occult metastasis to the CLNs and thus avoids thoracotomy.

A prospective, randomized trial of cognitive intervention for postoperative pain.

A single-blind, randomized prospective trial was performed at a university hospital to determine if preoperative relaxation training will decrease pain and narcotic demand postoperatively. A convenience sample of 49 patients undergoing lumbar and cervical spine surgery was randomized to receive instruction on relaxation techniques or routine preoperative information before surgery. Pain score and narcotic demand in the first 48 hours after surgery were the primary outcomes. Pain scores were higher in the relaxation (4.8 +/- 1.7) versus the standard preparation group (3.9 +/- 1.7) on postoperative day one (POD) 1, but lower on POD 2 (3.9 +/- 1.9 vs 4.1 +/- 1.9), whereas narcotic use (milligrams of IV morphine per hour) was higher in the relaxation group on POD 1 (1.14 +/- 0.94 vs 0.54 +/- 0.55) and POD 2 (0.86 +/- 0.73 vs 0.50 +/- 0.61). The differences were significant for narcotic demand (P = 0.01) but not for pain (P = 0.94). In conclusion, our results could not support the use of relaxation training for reducing postoperative pain and narcotic demand in this selected surgical population.

Malignant meningioma: computed tomography and magnetic resonance imaging characteristics.

Malignant meningioma is a relatively rare subtype of meningioma demonstrating an aggressive growth pattern, distinct histologic features, and a propensity for recurrence following surgical resection. There has been little consensus regarding imaging features of malignant meningioma, and typically the degree of tumor aggressiveness is determined by pathology. Here we describe a case of malignant meningioma determined to be benign at initial biopsy. Computed tomography (CT) and magnetic resonance (MR) imaging are reviewed with discussion of the aggressive features seen at presentation.