Malignant tracheoesophageal fistula treated with septal occluder device.

Septal occluder devices can be used with palliative intent to close tracheoesophageal fistulas and improve the quality of life of patients.

Venetoclax-associated interstitial pneumonitis.

Venetoclax is a selective inhibitor of the antiapoptotic protein B-cell lymphoma 2 (BCL-2). It is approved for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and acute myeloid leukemia (AML) in combination with chemotherapy or hypomethylating agents. Interstitial pneumonitis due to venetoclax has not been described in the literature. We describe a case of a 79-year-old female who experienced SLL relapse and developed interstitial pneumonitis associated with venetoclax, which completely resolved after discontinuation of the medication.

The killifish germline regulates longevity and somatic repair in a sex-specific manner.

Classical evolutionary theories propose tradeoffs among reproduction, damage repair and lifespan. However, the specific role of the germline in shaping vertebrate aging remains largely unknown. In this study, we used the turquoise killifish (Nothobranchius furzeri) to genetically arrest germline development at discrete stages and examine how different modes of infertility impact life history. We first constructed a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. We show here that germline depletion-but not arresting germline differentiation-enhances damage repair in female killifish. Conversely, germline-depleted males instead showed an extension in lifespan and rejuvenated metabolic functions. Through further transcriptomic analysis, we highlight enrichment of pro-longevity pathways and genes in germline-depleted male killifish and demonstrate functional conservation of how these factors may regulate longevity in germline-depleted Caenorhabditis elegans. Our results, therefore, demonstrate that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative responses to classical evolutionary tradeoffs.

Diffuse alveolar haemorrhage due to atypical hemolytic uremic syndrome (aHUS) associated with COVID-19.

Delayed presentation of atypical HUS after COVID-19 with diffuse alveolar haemorrhage is uncommon and can be life threatening.

A Fatal Case of Legionella bozemanii Pneumonia in an Immunocompetent Patient.

Legionella bozemanii pneumonia is a rare form of Legionnaires' disease caused by the bacterium Legionella bozemanii. It is well known to cause pneumonia in immunocompromised patients and has rarely been reported in immunocompetent hosts. We describe a case of a 59-year-old immunocompetent female presented with pneumonia, acute respiratory failure, acute respiratory distress, and septic shock, who was treated with azithromycin, goal-directed resuscitation, and extracorporeal membrane oxygenation (ECMO) but did not survive. Clinicians should have high suspicion of rare legionella pathogens as causative agents for pneumonia.

Impact of Blood Products Transfusion on Patients in the Immediate Post-Lung Transplant Period: A Cohort Study.

BACKGROUND Anemia is common in post-transplant patients. Blood product transfusion is associated with mortality and rejection in solid organ transplants. In lung transplant recipients, transfusion predisposes to primary graft dysfunction (PGD). The adverse effects and associated mortality of perioperative transfusions in lung transplant recipients have not been evaluated. This study examined the effects of perioperative blood transfusions in lung transplant recipients. MATERIAL AND METHODS We conducted a retrospective study of the effects of blood product transfusions in patients who received single- or double-lung transplantation at Houston Methodist Hospital between August 2017 and September 2019. Univariable and multiple logistic regression modeling were used to determine the characteristics associated with single events as well as a composite outcome within 30 days (including mortality, acute myocardial infarction, acute stroke, lower respiratory tract infection, urinary tract infection, surgical site infections, or PGD). RESULTS A total of 232 patients received lung transplants between December 2015 and September 2019 at our center. Univariable analysis revealed an increased risk of PGD (P<0.001), more mechanical ventilation days (P<0.001), more ICU days post-transplant (P<0.001), and greater need for ECMO support (P=0.001) in patients who received blood product transfusions. In univariate analysis, the composite outcome was also more common (P=0.01) in patients who received any transfusion perioperatively. A total of 7 patients died within 30 days from transplant, and they were all in the transfused group. CONCLUSIONS Among lung transplant recipients, PGD, ICU days, need for mechanical ventilation and ECMO support, and total composite events were significantly greater in patients who received blood transfusion perioperatively.

Bronchial artery embolization for the treatment of delayed massive hemoptysis due to a retained bullet.

Bronchial artery embolization is a feasible option for treating hemoptysis caused by foreign objects in patients who are not candidates for surgery.

The killifish germline regulates longevity and somatic repair in a sex-specific manner.

Classical evolutionary theories propose tradeoffs between reproduction, damage repair, and lifespan. However, the specific role of the germline in shaping vertebrate aging remains largely unknown. Here, we use the turquoise killifish ( N. furzeri ) to genetically arrest germline development at discrete stages, and examine how different modes of infertility impact life-history. We first construct a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. Next, we show that germline depletion - but not arresting germline differentiation - enhances damage repair in female killifish. Conversely, germline-depleted males instead showed an extension in lifespan and rejuvenated metabolic functions. Through further transcriptomic analysis, we highlight enrichment of pro-longevity pathways and genes in germline-depleted male killifish and demonstrate functional conservation of how these factors may regulate longevity in germline-depleted C. elegans . Our results therefore demonstrate that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative responses to classical evolutionary tradeoffs.

A short peptide protects from age-onset proteotoxicity.

Aberrant protein aggregation jeopardizes cellular functionality and underlies the development of a myriad of late-onset maladies including Alzheimer's disease (AD) and Huntington's disease (HD). Accordingly, molecules that mitigate the toxicity of hazardous protein aggregates are of great interest as potential future therapeutics. Here we asked whether a small peptide, composed of five amino acids (5MER peptide) that was derived from the human pro-inflammatory CD44 protein, could protect model nematodes from the toxicity of aggregative proteins that underlie the development of neurodegenerative disorders in humans. We found that the 5MER peptide mitigates the toxicity that stems from both; the AD-causing Aß peptide and a stretch of poly-glutamine that is accountable for the development of several disorders including HD, while minimally affecting lifespan. This protection was dependent on the activity of aging-regulating transcription factors and associated with enhanced Aß and polyQ35-YFP aggregation. A transcriptomic analysis unveiled that the peptide modifies signaling pathways, thereby modulating the expression of various genes, including these, which are known as protein homeostasis (proteostasis) regulators such as txt-13 and modifiers of proteasome activity. The knockdown of txt-13 protects worms from proteotoxicity to the same extent as the 5MER peptide, suggesting that the peptide activates the transcellular chaperone signaling to promote proteostasis. Together, our results propose that the 5MER peptide should be considered as a component of future therapeutic cocktails for the treatment of neurodegenerative maladies.

Cardiac imaging in rheumatic heart disease and future developments.

Rheumatic heart disease (RHD) is the most common cause of valvular heart disease worldwide, affecting millions, especially in low- and middle-income countries. Multiple imaging modalities such as cardiac CT, cardiac MRI, and three-dimensional echocardiography may be utilized in diagnosing, screening, and managing RHD. However, two-dimensional transthoracic echocardiography remains the cornerstone of imaging in RHD. Criteria developed by the World Heart Foundation in 2012 sought to unify the diagnostic imaging criteria for RHD, but concerns remain regarding their complexity and reproducibility. In the intervening years, further measures have been developed to find a balance between simplicity and accuracy. Nonetheless, there remain significant unresolved problems within imaging in RHD, including the development of a practical and sensitive screening tool to identify patients with RHD. The emergence of handheld echocardiography has the potential to revolutionize RHD management in resource-poor settings, but its role as a screening or diagnostic tool is yet to be fully established. The dramatic evolution of imaging modalities over the last few decades has not addressed RHD compared to other forms of structural heart disease. In this review, we examine the current and latest developments concerning cardiac imaging and RHD.

Prognostic Value of Late Gadolinium Enhancement Detected on Cardiac Magnetic Resonance in Cardiac Sarcoidosis.

BACKGROUND: Sarcoidosis is a complex multisystem inflammatory disorder, with approximately 5% of patients having overt cardiac involvement. Patients with cardiac sarcoidosis are at an increased risk of both ventricular arrhythmias and sudden cardiac death. Previous studies have shown that the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with an increased risk of mortality and ventricular arrhythmias and may be useful in predicting prognosis. OBJECTIVES: This systematic review and meta-analysis assessed the value of LGE on CMR imaging in predicting prognosis for patients with known or suspected cardiac sarcoidosis. METHODS: The authors searched the Embase and MEDLINE databases from inception to March 2022 for studies reporting individuals with known or suspected cardiac sarcoidosis referred for CMR with LGE. Outcomes were defined as all-cause mortality, ventricular arrhythmia, or a composite outcome of either death or ventricular arrhythmias. The primary analysis evaluated these outcomes according to the presence of LGE. A secondary analysis evaluated outcomes specifically according to the presence of biventricular LGE. RESULTS: Thirteen studies were included (1,318 participants) in the analysis, with an average participant age of 52.0 years and LGE prevalence of 13% to 70% over a follow-up of 3.1 years. Patients with LGE on CMR vs those without had higher odds of ventricular arrhythmias (odds ratio [OR]: 20.3; 95% CI: 8.1-51.0), all-cause mortality (OR: 3.45; 95% CI: 1.6-7.3), and the composite of both (OR: 9.2; 95% CI: 5.1-16.7). Right ventricular LGE is invariably accompanied by left ventricular LGE. Biventricular LGE is also associated with markedly increased odds of ventricular arrhythmias (OR: 43.6; 95% CI: 16.2-117.2). CONCLUSIONS: Patients with known or suspected cardiac sarcoidosis with LGE on CMR have significantly increased odds of both ventricular arrhythmias and all-cause mortality. The presence of biventricular LGE may confer additional prognostic information regarding arrhythmogenic risk.

A Novel System to Increase Yield of Manufacturing Test of an RF Transceiver through Application of Machine Learning.

Electronic manufacturing and design companies maintain test sites for a range of products. These products are designed according to the end-user requirements. The end user requirement, then, determines which of the proof of design and manufacturing tests are needed. Test sites are designed to carry out two things, i.e., proof of design and manufacturing tests. The team responsible for designing test sites considers several parameters like deployment cost, test time, test coverage, etc. In this study, an automated test site using a supervised machine learning algorithm for testing an ultra-high frequency (UHF) transceiver is presented. The test site is designed in three steps. Firstly, an initial manual test site is designed. Secondly, the manual design is upgraded into a fully automated test site. And finally supervised machine learning is applied to the automated design to further enhance the capability. The manual test site setup is required to streamline the test sequence and validate the control and measurements taken from the test equipment and unit under test (UUT) performance. The manual test results showed a high test time, and some inconsistencies were observed when the test operator was required to change component values to tune the UUT. There was also a sudden increase in the UUT quantities and so, to cater for this, the test site is upgraded to an automated test site while the issue of inconsistencies is resolved through the application of machine learning. The automated test site significantly reduced test time per UUT. To support the test operator in selecting the correct component value the first time, a supervised machine learning algorithm is applied. The results show an overall improvement in terms of reduced test time, increased consistency, and improved quality through automation and machine learning.

Laryngeal Embryonal Rhabdomyosarcoma: A rare adult neoplasm.

The embryonal subtype of rhabdomyosarcoma is the most frequent, commonly seen in children. However, it is uncommon to discover this subtype in adults, especially in the larynx. We presented a rare case of a 63 years old man who presented with worsening hoarseness, dysphagia for solids, and dyspnea and was later diagnosed with embryonal rhabdomyosarcoma of the larynx.

Neuropeptide signaling and SKN-1 orchestrate differential responses of the proteostasis network to dissimilar proteotoxic insults.

The protein homeostasis (proteostasis) network (PN) encompasses mechanisms that maintain proteome integrity by controlling various biological functions. Loss of proteostasis leads to toxic protein aggregation (proteotoxicity), which underlies the manifestation of neurodegeneration. How the PN responds to dissimilar proteotoxic challenges and how these responses are regulated at the organismal level are largely unknown. Here, we report that, while torsin chaperones protect from the toxicity of neurodegeneration-causing polyglutamine stretches, they exacerbate the toxicity of the Alzheimer's disease-causing Aß peptide in neurons and muscles. These opposing effects are accompanied by differential modulations of gene expression, including that of three neuropeptides that are involved in tailoring the organismal response to dissimilar proteotoxic insults. This mechanism is regulated by insulin/IGF signaling and the transcription factor SKN-1/NRF. Our work delineates a mechanism by which the PN orchestrates differential responses to dissimilar proteotoxic challenges and points at potential targets for therapeutic interventions.

Angioembolisation for the Treatment of Pseudo-aneurysm of Internal Maxillary Artery.

Pseudo-aneurysm of internal maxillary artery, following a road traffic accident, is a rare clinical scenario. The consequence of pseudo-aneurysm may be spontaneous rupture of the arterial wall, which may eventually lead to life-threatening hemorrhage. We report a case of a 20-year male who presented with recurrent epistaxis. CT scan was performed, which revealed a pseudo-aneurysm of the internal maxillary artery; this was successfully treated by angioembolisation. Similar cases of traumatic pseudo-aneurysms have been reported, however, none presented with recurrent epistaxis after management of pan-facial fractures. Key Words: Epistaxis, Pseudo-aneurysm, Angioembolisation, Pan-facial fracture.

Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction.

The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of "Xenobiotic Detoxification Program" (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span.

Post parotidectomy facial nerve palsy: A retrospective analysis.

BACKGROUND &OBJECTIVES: Transient paralysis of facial nerve is seen to vary from 15 % to 66 % in post-parotid surgery. The objective of this study was to find out the complications in post-parotidectomy with regards to facial nerve dysfunction since it is a vital structure encountered in parotid surgeries. METHODS: This was a retrospective study through non probability convenient sampling technique carried from September 2010 to January 2019 in the Department of Otorhinolaryngology, Dow University of Health Sciences, Dr. Ruth K.M.Pfau Civil Hospital, Karachi. Clinical data were recorded from 75 patients and out of them 70 patients had undergone surgery with parotid gland tumours and were reported on the morphology, age, sex, surgical procedure and complications, particularly facial nerve dysfunctions. In most cases ante-grade technique was performed to identify the facial nerve, whereas retrograde technique was used in recurring tumours, and in difficult cases. The stimulator of the nerve has not been used. The nature or severity of Facial nerve dysfunction was assessed in terms of either it is, permanent or temporary, total or incomplete in respect to its branches. RESULTS: Among total 75 patients; the mean age was 38.75 ± 9.26 years with male to female ratio of 1:1. Majority of the patients were diagnosed as pleomorphic adenoma, i.e. 78.6% after which 12% were diagnosed as mucoepidermoid carcinoma. 88.6% of patients had superficial parotidectomy and 11.4% of patients had total parotidectomy. About 75% of patients had no complications. 5(7.1%) patients had complete facial nerve palsy. Damage to the mandibular, buccal and temporozygomatic branch was observed in 10(14%), 2(3%) and 1(1.4%) patients respectively. CONCLUSION: The most prevalent benign parotid tumour in this study was pleomorphic adenoma. After performing parotid surgery, it was predicted that the rate of complications related to the facial nerve injury was reduced as compared to the previous studies.

The insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in Caenorhabditis elegans.

Although aging-regulating pathways were discovered a few decades ago, it is not entirely clear how their activities are orchestrated, to govern lifespan and proteostasis at the organismal level. Here, we utilized the nematode Caenorhabditis elegans to examine whether the alteration of aging, by reducing the activity of the Insulin/IGF signaling (IIS) cascade, affects protein SUMOylation. We found that IIS activity promotes the SUMOylation of the germline protein, CAR-1, thereby shortening lifespan and impairing proteostasis. In contrast, the expression of mutated CAR-1, that cannot be SUMOylated at residue 185, extends lifespan and enhances proteostasis. A mechanistic analysis indicated that CAR-1 mediates its aging-altering functions, at least partially, through the notch-like receptor glp-1. Our findings unveil a novel regulatory axis in which SUMOylation is utilized to integrate the aging-controlling functions of the IIS and of the germline and provide new insights into the roles of SUMOylation in the regulation of organismal aging.

Association of methacholine challenge test with diagnosis of chronic lung allograft dysfunction in lung transplant patients.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a complication of lung transplantation. We sought to determine whether bronchial hyperresponsiveness detected by the methacholine challenge test (MCT) at 3 months after lung transplant (LT) predicts the development of CLAD. METHODS: We performed a retrospective cohort study of 140 LT patients between 1/2008 and 6/2014 who underwent MCT at 3 months after LT. Pearson's chi-squared test and Kruskal-Wallis test were used to compare categorical and continuous variables, respectively. Cox proportional hazards modeling was used to evaluate the association between CLAD and MCT. RESULTS: Methacholine challenge test+ was associated with the development of overall CLAD (adjusted hazards ratio [aHR]: 3.47; 95% confidence interval [95% CI]: 1.71, 7.03; P = 0.001) and CLAD within 3 years (aHR: 4.98; 95%CI: 1.84, 13.48; P = 0.002). Subgroup analysis showed that MCT (+) is associated with overall CLAD in single lung transplant (SLT) (aHR: 8.18; 95% CI: 2.22, 30.09; P = 0.002), double lung transplant (DLT) (aHR: 3.27; 95% CI: 1.22, 8.78; P = 0.02) and CLAD within 3 years in DLT patients (aHR: 6.76; 95% CI: 1.71, 26.74; P = 0.01). CONCLUSION: Methacholine challenge test+ at 3 months after LT is associated with the development of overall CLAD. Positive MCT could predict the development of early CLAD within 3 years in DLT patients.

A rare case of pulmonary cement embolism in a lung transplant patient.

Pulmonary cement embolism (PCE) is a complication of percutaneous vertebral augmentation techniques. PCE in lung transplant patient population has not been reported. We report a case 57-year-old male patient with double lung transplant secondary to idiopathic pulmonary fibrosis presented with shortness of breath after vertebroplasty. CTA chest showed thin dense opacities within the bilateral pulmonary arteries consistent with pulmonary cement embolism. The patient was treated with therapeutic enoxaparin and remained stable at one year follow up.