Prostatic Artery Embolization in Patients with Refractory Lower Urinary Tract Symptoms after a Prior Minimally Invasive Surgical Treatment.

The purpose of this study was to report on prostatic artery embolization (PAE) outcomes in patients with refractory or recurrent lower urinary tract symptoms (LUTSs) due to benign prostatic hyperplasia (BPH) who had previously undergone a minimally invasive surgical technique (MIST). A single-center retrospective study identified 16 eligible patients. Baseline prostate volume at the time of PAE was 112.9 mL (SD ± 52.7). There were no adverse events throughout the follow-up period. There was significant improvement in International Prostate Symptom Score and quality of life from baseline of 23.5 (SD ± 5.1) and 4.9 (SD ± 0.9), respectively, to the last follow-up of 11.6 (SD ± 7.2) and 2 (SD ± 1.6), respectively. There was nonsignificant improvement in sexual function after PAE compared with baseline after MIST. PAE can be a safe and effective treatment in patients who have undergone prior MIST without negatively impacting erectile or ejaculatory function.

A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.

Failure of septation of the interventricular septum (IVS) is the most common congenital heart defect (CHD), but mechanisms for patterning the IVS are largely unknown. We show that a Tbx5+/Mef2cAHF+ progenitor lineage forms a compartment boundary bisecting the IVS. This coordinated population originates at a first- and second heart field interface, subsequently forming a morphogenetic nexus. Ablation of Tbx5+/Mef2cAHF+ progenitors cause IVS disorganization, right ventricular hypoplasia and mixing of IVS lineages. Reduced dosage of the CHD transcription factor TBX5 disrupts boundary position and integrity, resulting in ventricular septation defects (VSDs) and patterning defects, including Slit2 and Ntn1 misexpression. Reducing NTN1 dosage partly rescues cardiac defects in Tbx5 mutant embryos. Loss of Slit2 or Ntn1 causes VSDs and perturbed septal lineage distributions. Thus, we identify essential cues that direct progenitors to pattern a compartment boundary for proper cardiac septation, revealing new mechanisms for cardiac birth defects.

Trazodone for sleep disturbance in opioid dependent patients maintained on buprenorphine: A double blind, placebo-controlled trial.

BACKGROUND: Sleep disturbances are seen even in individuals on opioid agonist treatment (OAT). Established pharmacotherapy for sleep disturbances such as benzodiazepines have misuse potential and increased mortality risk in patients with OAT. No study has explored the role of trazodone on sleep disturbance in individuals maintained on buprenorphine. We aimed to assess the efficacy of trazodone in improving sleep disturbance among individuals maintained on buprenorphine. METHODS: The study was a double-blind, placebo-controlled, parallel, randomised trial. Adult males (18-60 years) stabilised on buprenorphine with Pittsburgh Sleep Quality Index (PSQI) score of above five, without other psychiatric comorbidity were randomised to receive either trazodone (50-150mg per day) or placebo. Sleep-50 questionnaire, Epworth Sleepiness Scale (ESS), Brief Pain Inventory (BPI), Clinical Opiate Withdrawal Scale (COWS), Depression, Anxiety and Stress Scale (DASS)-21, Visual Analogue Scale (VAS) for opioid craving, and PSQI were assessed at baseline and at the end of six weeks. RESULTS: Fifty-one patients were allocated to trazodone arm and 49 to placebo arm. Side-effects of trazodone were minimal and well-tolerated with comparable discontiuation rates between both groups. Significantly greater proportion of patients on trazodone (82%, mean dose 101.9 mg) had PSQI scores five or less than those on placebo (16%) at the end of six weeks. Sleep improvement was in various components like sleep quality, latency, efficiency, and duration of sleep. CONCLUSION: Trazodone is well-tolerated and effective in improving sleep disturbances in individuals with opioid dependence maintained on buprenorphine over a six-week period.

Outcomes of Patients with Positive Interim Positron Emission Tomography (PET) Continuing ABVD in the Clinical Setting.

Recent prospective clinical trial data suggest that patients with Hodgkin's lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome.

Inpatient re-rupture of a middle meningeal arteriovenous fistula after traumatic brain injury.

We present a case of a spontaneous second intraparenchymal hemorrhage (IPH) following patient admission for a traumatic brain injury with an initial traumatic IPH. After a subsequent review of all imaging, it was concluded that the patient had a traumatic middle meningeal associated dural arterial venous fistula (MMAVF) which re-ruptured during admission, and the MMAVF was overlooked as a potential contributor to the initial traumatic IPH for which the patient was admitted. A 49-year old man presented with right temporal IPH following an ATV accident and was found to have a right MMAVF on cerebral angiography. The MMAVF appeared on angiography to be unruptured, and therefore was not immediately treated. Later in admission, the patient suffered a new spontaneous IPH ipsilateral to the MMAVF, suggesting a re-rupture. Endovascular transarterial embolization with ethyl vinyl alcohol resulted in complete obliteration of the MMAVF. The patient tolerated treatment well and went on to make a good recovery as of last post-operative imaging at 8 months. Hence, MMAVFs may be present in the setting of IPH following a traumatic brain injury which warrants maintaining a high level of suspicion and low threshold for intervention as they can cause secondary spontaneous intracranial hemorrhage. The absence of notable subdural or extradural hemorrhage on imaging should not exclude rupture. Transarterial embolization with an ethylene vinyl alcohol copolymer is an effective treatment modality.

Controversies in Prostate Artery Embolization: Future Best Practice.

Prevalence of lower urinary tract symptoms secondary to benign prostatic hyperplasia is correlated with age. Men seeking treatment options with a low side effect profile often turn to prostate artery embolization (PAE). PAE continues to be refined with advanced tools and optimized techniques. Nonetheless, there exist controversies in terms of best practices for the management of lower urinary track symptoms (LUTS) with PAE. These controversies are essential for medical progress. Herein we suggest best practices moving forward based on currently available data. Given extensive safety data, we recommend PAE be considered alongside medical management and as a precursor to surgery. Given demonstrated efficacy across gland sizes, PAE can be performed in a single session, ideally in a hybrid angio-CT suite, without preoperative cross-sectional imaging. PAE should be initially performed with 300- to 500-µm size particles, and instead consider exploring other particles and sizes for repeat PAE. Finally, PAE can also be considered as first-line option for recurrent disease given the efficacy and excellent safety profile. This article is not meant to purport a dogma, but rather to serve as a guide to the experienced practitioner in challenging his or her own biases when performing PAE.

Role of interventional oncology in hepatocellular carcinoma: Future best practice beyond current guidelines.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Liver transplant remains the goal of curative treatment, but limited supply of organs decreases accessibility and prolongs waiting time to transplantation. Therefore, interventional oncology therapies have been used to treat the majority of HCC patients, including those awaiting transplant. The Barcelona Clinic Liver Cancer (BCLC) classification is the most widely used staging system in management of HCC that helps allocate treatments. Since its inception in 1999, it was updated for the fifth time in November 2021 and for the first time shaped by expert opinions outside the core BCLC group. The most recent version includes additional options for early-stage disease, substratifies intermediate disease into three groups, and lists alternates to Sorafenib that can double the expected survival of advanced-stage disease. The group also proposed a new BCLC staging schema for disease progression, and endorsed treatment stage migration (TSM) directly into the main staging and treatment algorithm. This article reviews the recent developments underlying the current BCLC guidelines and highlights ongoing research, particularly involving radioembolization, that will shape future best practice.

Mortality and Clinical Outcomes among Patients with COVID-19 and Diabetes.

Background Diabetes mellitus (DM) is a decisive risk factor for severe illness in coronavirus disease 2019 (COVID-19). India is home to a large number of people with DM, and many of them were infected with COVID-19. It is critical to understand the impact of DM on mortality and other clinical outcomes of COVID-19 infection from this region. Aims The primary objective of our study was to analyze the mortality rate in people with DM infected with COVID-19. The secondary objectives were to assess the effect of various comorbidities on mortality and study the impact of DM on other clinical outcomes. Methods This is a retrospective study of COVID-19 infected patients admitted to a tertiary care hospital in north India in the early phase of the pandemic. Results Of the 1211 cases admitted, 19 were excluded because of incomplete data, and 1192 cases were finally considered for analysis. DM constituted 26.8% of total patients. The overall mortality rate was 6.1%, and the rate was 10.7% in the presence of diabetes (p < 0.01, OR 2.55). In univariate analysis, increased age, chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and cancer were associated with mortality. On multiple logistic regression, the independent predictors of mortality were CAD, CKD, and cancer. Breathlessness and low SpO2 at presentation, extensive involvement in CXR, and elevated ANC/ALC ratio were also significantly associated with mortality. Conclusions The presence of comorbidities such as DM, hypertension, CAD, CKD, and cancer strongly predict the risk of mortality in COVID-19 infection. Early triaging and aggressive therapy of patients with these comorbidities can optimize clinical outcomes.

Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease.

Haploinsufficiency of transcriptional regulators causes human congenital heart disease (CHD); however, the underlying CHD gene regulatory network (GRN) imbalances are unknown. Here, we define transcriptional consequences of reduced dosage of the CHD transcription factor, TBX5, in individual cells during cardiomyocyte differentiation from human induced pluripotent stem cells (iPSCs). We discovered highly sensitive dysregulation of TBX5-dependent pathways-including lineage decisions and genes associated with heart development, cardiomyocyte function, and CHD genetics-in discrete subpopulations of cardiomyocytes. Spatial transcriptomic mapping revealed chamber-restricted expression for many TBX5-sensitive transcripts. GRN analysis indicated that cardiac network stability, including vulnerable CHD-linked nodes, is sensitive to TBX5 dosage. A GRN-predicted genetic interaction between Tbx5 and Mef2c, manifesting as ventricular septation defects, was validated in mice. These results demonstrate exquisite and diverse sensitivity to TBX5 dosage in heterogeneous subsets of iPSC-derived cardiomyocytes and predicts candidate GRNs for human CHDs, with implications for quantitative transcriptional regulation in disease.

In Silico Labeling: Predicting Fluorescent Labels in Unlabeled Images.

Microscopy is a central method in life sciences. Many popular methods, such as antibody labeling, are used to add physical fluorescent labels to specific cellular constituents. However, these approaches have significant drawbacks, including inconsistency; limitations in the number of simultaneous labels because of spectral overlap; and necessary perturbations of the experiment, such as fixing the cells, to generate the measurement. Here, we show that a computational machine-learning approach, which we call "in silico labeling" (ISL), reliably predicts some fluorescent labels from transmitted-light images of unlabeled fixed or live biological samples. ISL predicts a range of labels, such as those for nuclei, cell type (e.g., neural), and cell state (e.g., cell death). Because prediction happens in silico, the method is consistent, is not limited by spectral overlap, and does not disturb the experiment. ISL generates biological measurements that would otherwise be problematic or impossible to acquire.

Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.

Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRß signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell-cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, while cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion.

Idiopathic Intracranial Hypertension in a pubertal paediatric Indian patient.

BACKGROUND: Idiopathic Intracranial Hypertension (IIH) is characterised by raised intracranial pressure (ICP) with normal cerebrospinal fluid (CSF) composition and absence of hydrocephalus or space occupying lesions. IIH is a rare disease in children. It can lead to visual impairment but prompt diagnosis and treatment in most of the cases will prevent potentially permanent visual loss. OBJECTIVE: To report a rare case of Idiopathic Intracranial Hypertension in a pubertal child, clinical features, and findings of Magnetic Resonance Imaging (MRI) and visual field of this case. CASE: An adolescent girl aged 14 years presented with headache and transient visual obscuration for two weeks. On examination, findings (fundus, visual field and MRI) were suggestive of Idiopathic intracranial hypertension. She did not have any classical predisposing risk factors. She recovered very well with acetazolamide and short term steroid therapy with no sequelae and clinical recurrence over a follow up of 12 months. CONCLUSION: This is a rare case of IIH in a child, which was confirmed on the MRI and visual field testing.