Intravenous ketamine successfully treats treatment-resistant catatonia in schizophrenia: A case report.

BACKGROUND: Benzodiazepines and electroconvulsive therapy (ECT) are mainstay treatments for catatonia, a potentially life-threatening psychomotor syndrome characterized by a range of symptoms, including immobility, mutism, stupor, posturing, and sometimes even agitation. It can be a manifestation of various underlying psychiatric or medical conditions, such as schizophrenia, mood disorders, or neurological disorders. When conventional treatments fail to alleviate symptoms, ketamine, a dissociative anesthetic, has emerged as a potential therapeutic option for catatonia. However, its precise mechanism of action in treating catatonia remains to be fully elucidated. The use of ketamine in treating treatment-resistant catatonia in patients with schizophrenia has not been described. METHODS: We describe a unique case of a 77-year-old female with schizophrenia for 15 years who presented with hallucinations, generalized weakness, immobility, stupor, and mutism consistent with severe catatonia. The electroencephalogram did not show seizures, and brain imaging was negative for stroke. Her catatonia was resistant to treatment with benzodiazepines and haloperidol. However, ECT was unavailable due to the COVID-19 pandemic. She was successfully treated with a single intravenous infusion of ketamine administered at a dose of 0.5 mg/kg over 40 min with complete rapid recovery and remained stable as an outpatient. RESULTS: Intravenous ketamine single infusion may be a safe and feasible option in schizophrenia patients with drug-resistant catatonia, particularly in patients for whom standard therapies are ineffective. However, its use should be approached cautiously due to the risk of exacerbation of psychosis in patients with schizophrenia. CONCLUSIONS: Further research is warranted to better understand the role of ketamine in the management of catatonia in this patient population.

Cathepsin B promotes Aß proteotoxicity by modulating aging regulating mechanisms.

While the activities of certain proteases promote proteostasis and prevent neurodegeneration-associated phenotypes, the protease cathepsin B (CTSB) enhances proteotoxicity in Alzheimer's disease (AD) model mice, and its levels are elevated in brains of AD patients. How CTSB exacerbates the toxicity of the AD-causing Amyloid ß (Aß) peptide is controversial. Using an activity-based probe, aging-altering interventions and the nematode C. elegans, we discovered that the CTSB CPR-6 promotes Aß proteotoxicity but mitigates the toxicity of polyQ stretches. While the knockdown of cpr-6 does not affect lifespan, it alleviates Aß toxicity by reducing the expression of swsn-3 and elevating the level of the protein SMK-1, both involved in the regulation of aging. These observations unveil a mechanism by which CTSB aggravates Aß-mediated toxicity, indicate that it plays opposing roles in the face of distinct proteotoxic insults and highlight the importance of tailoring specific remedies for distinct neurodegenerative disorders.

Subglottic adenoid cystic carcinoma associated with pulmonary Langerhans cell histiocytosis.

Pulmonary Langerhans cell histiocytosis can be associated with subglottic adenoid cystic carcinoma.

Miliary sarcoidosis.

Miliary patterns on chest imaging of the lung can be associated with sarcoidosis.

Do Posterior Neck Lumps Need Ultrasound Evaluation: A Case Series of 623 Neck Ultrasound Studies at a Single Institution.

INTRODUCTION/OBJECTIVES: Neck lumps are a common presentation to primary care services. The aetiology of posterior neck lumps is poorly explored in the literature, and therefore remain a concern to patients and clinicians. This often results in an urgent referral for ultrasound assessment. The authors of this study sought to evaluate the aetiology of posterior neck lumps from a radiological perspective, to assess whether ultrasound can be used as a useful adjunct, rather than a first-line urgent investigation. METHODS: A retrospective case series was carried out, examining all primary care referred ultrasound studies for assessment of posterior neck lumps, performed at a single institution in Essex, United Kingdom, over a period of over 10 years dating between 2nd February 2012 to 8th November 2022. Data was collected on: patient age at the time of study, patient sex, whether the lump was single or multiple as palpated and documented by the primary care physician, size of the lump to the nearest 0.5 cm as documented on ultrasound using the longest dimension, sonographic diagnosis and any follow up imaging (not limited to ultrasound). RESULTS: A total of 623 neck ultrasounds were performed on 615 adults. Of the overall radiological diagnoses made from the 623 scans, 555 (89.09%) scans were benign, 63 (10.11%) scans had no lump found on sonography, and 3 (0.48%) scans showed malignancy. In the remaining 2 (0.32%) scans, the lump was deemed indeterminate. The most common aetiologies for benign lumps were due to: normal lymph nodes (n = 263; 42.21%), lipomas (n = 152; 24.39%), and benign dermal cysts (n = 105; 16.85%). All 3 malignant cases had co-existing anterior and posterior neck lumps. CONCLUSIONS: Given that the overwhelming majority of posterior neck lumps in our study had benign findings, we propose that patients with solitary or even multiple posterior neck lumps alone, regardless of size can either be investigated routinely or can be reassured depending on other clinical examination characteristics. Patients who have the presence of co-existing anterior and posterior neck palpable neck lumps justifies urgent or 2-week wait radiological investigation.

Recurrent Pleural Effusion Associated With Candida Albicans Infection in Transplanted Kidney: A Case Report.

Recurrent pleural effusions are associated with significant morbidity and mortality. Pleural effusions are frequently seen in patients with chronic renal failure due to fluid retention. Pleural effusions in renal transplant patients are usually related to secondary pulmonary infections, surgical complications, drug toxicities, or post-transplant lymphoproliferative disorder (PTLD). We describe an unusual cause of recurrent pleural effusion attributed to fungal infection in a transplanted kidney due to activation of the renin-angiotensin-aldosterone system (RAAS), successfully treated with antifungal medications that led to complete resolution of pleural effusion.

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.

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.

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.

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.

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.

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.

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.