Citations

The utilization of vasopressin receptor antagonists, known as vaptans, in the management of hyponatremia among patients afflicted with the syndrome of inappropriate antidiuretic hormone (SIADH) remains a contentious subject. This meta-analysis aimed to evaluate the safety and efficacy of vaptans for treating chronic hyponatremia in adult SIADH patients. Clinical trials and observational studies were identified by a systematic search using MEDLINE, EMBASE, and Cochrane Database from inception through September 2022. The inclusion criteria were the studies that reported vaptans’ safety or efficacy outcomes compared to placebo or standard therapies. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD 42022357307). Five studies were identified, comprising three RCTs and two cohort studies, enrolling a total of 1840 participants. Regarding short-term efficacy on days 4–5, vaptans exhibited a significant increase in serum sodium concentration from the baseline in comparison to the control group, with a weighted mean difference of 4.77 mmol/L (95% CI, 3.57, 5.96; I2 = 34%). In terms of safety outcomes, the pooled incidence rates of overcorrection were 13.1% (95% CI 4.3, 33.6; I2 = 92%) in the vaptans group and 3.3% (95% CI 1.6, 6.6; I2 = 27%) in the control group. Despite the higher correction rate linked to vaptans, with an OR of 5.72 (95% CI 3.38, 9.70; I2 = 0%), no cases of osmotic demyelination syndrome were observed. Our meta-analysis comprehensively summarizes the efficacy and effect size of vaptans in managing SIADH. While vaptans effectively raise the serum sodium concentration compared to placebo/fluid restriction, clinicians should exercise caution regarding the potential for overcorrection.

Abstract Background and aims Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. Methods A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. Results The TRI-SCORE was low (≤3) in 32%, intermediate (4–5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). Conclusions Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

Histopathology has remained a cornerstone for biomedical tissue assessment for over a century, with a resource-intensive workflow involving biopsy or excision, gross examination, sampling, tissue processing to snap frozen or formalin-fixed paraffin-embedded blocks, sectioning, staining, optical imaging, and microscopic assessment. Emerging chemical imaging approaches, including stimulated Raman scattering (SRS) microscopy, can directly measure inherent molecular composition in tissue (thereby dispensing with the need for tissue processing, sectioning, and using dyes) and can use artificial intelligence (AI) algorithms to provide high-quality images. Here we show the integration of SRS microscopy in a pathology workflow to rapidly record chemical information from minimally processed fresh-frozen prostate tissue. Instead of using thin sections, we record data from intact thick tissues and use optical sectioning to generate images from multiple planes. We use a deep learning–based processing pipeline to generate virtual hematoxylin and eosin images. Next, we extend the computational method to generate archival-quality images in minutes, which are equivalent to those obtained from hours/days-long formalin-fixed, paraffin-embedded processing. We assessed the quality of images from the perspective of enabling pathologists to make decisions, demonstrating that the virtual stained image quality was diagnostically useful and the interpathologist agreement on prostate cancer grade was not impacted. Finally, because this method does not wash away lipids and small molecules, we assessed the utility of lipid chemical composition in determining grade. Together, the combination of chemical imaging and AI provides novel capabilities for rapid assessments in pathology by reducing the complexity and burden of current workflows. Significance: Archival-quality (formalin-fixed paraffin-embedded), thin-section diagnostic images are obtained from thick-cut, fresh-frozen prostate tissues without dyes or stains to expedite cancer histopathology by combining SRS microscopy and machine learning.

Background/Objectives The COVID-19 pandemic motivated telemedicine care to decrease potential exposures for both patients and staff. We hypothesized that select breast surgical patients can be successfully evaluated pre-operatively with telemedicine. Methods With institutional review board approval, patients with telemedicine surgical consults between 1 March 2020 and 31 August 2020 were identified retrospectively from our prospective breast surgical registry. The frequency of successful pre-operative evaluation using telemedicine alone was assessed, defined as cases in which surgery was completed on the planned day without changes to the surgical plan after physical examination in the pre-operative area. Differences in disease presentation, patient characteristics, and complications were evaluated by whether the first in-person visit occurred on the day of surgery versus the prior. Results A total of 374 patients underwent breast surgery between 1 March 2020 and 31 August 2020, of which 96 (25.7%) had a telemedicine consultation. After the telemedicine visit, 38 patients (39.6%) had additional in-person visits with the breast surgeon prior to their operative date, and 58 patients (60.4%) did not. Forty-five patients underwent breast-conserving therapies, 41 mastectomies (25 with reconstruction), two axillary dissections, and eight excisional biopsies. All surgeries were completed on the planned operative day, with no changes in surgical plans. Patients with telemedicine only prior to surgery were more likely to speak English (100% vs. 92.1%, p = 0.02) and have lower body mass index (median 24.9 vs. 29.2, p = 0.01). The frequency of in-person pre-operative visits varied significantly by surgeon ( p < 0.001). Age, American Society of Anaesthesiologists score, distance from facility, clinical T/N category, surgery type, and complications did not differ between groups. Conclusions Telemedicine can be utilized successfully for select breast surgical patients, with the ability to proceed to surgery in the majority of patients without additional in-person visits.

AbstractPatients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease‐specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human‐platelet‐derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)‐like module‐containing mucin‐like hormone receptor‐like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll‐like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL‐1β), transforming growth factor‐beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7–9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T‐cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.

Susac Syndrome was first described as an inflammatory microangiopathy of the brain and retina. Since then, multiple articles have been published in attempts to improve the understanding of this rare disease. Clinically Susac Syndrome is known to present with triad of encephalopathy, sensorineural hearing loss and branch of retinal artery occlusion (BRAO), along with characteristic “snowball” or “spoke” appearing white matter lesions of the corpus callosum. It has been characterized by vast heterogeneity in terms of its presenting symptoms, severity, and clinical course. Although subset of patients present with severe forms of Susac Syndrome and can develop prominent residual neurologic deficits, it has been reported to be mostly non-life-threatening and only few fatal cases have been described in the literature. Based on the available case reports with fatal outcome, mortality has been related to the systemic complications either during acute disease flare or during chronic-progressive phase. We describe a case of fulminant Susac Syndrome complicated by the sudden and rapid progression of diffuse cerebral edema leading to brain herniation and ultimate brain death, in order to increase awareness of this rare and catastrophic complication.

Abstract Objectives: Periodic paralysis is a rare genetic condition characterized by episodes of neuromuscular weakness, often provoked by electrolyte abnormalities, physiologic stress, physical exertion, and diet. In addition to mutations in genes coding for skeletal muscle ion channels, in 2019, Gustavasson et al discovered that the MCM3AP gene could be responsible for periodic paralysis. In this study, we present 2 individuals with clinical episodes of periodic paralysis who have variants in the MCM3AP gene. Methods: Two unrelated probands were independently evaluated with clinical, genetic, and electrodiagnostic testing. Results: Proband 1 is a 46-year-old man who presented with decades of ongoing episodic weakness and fatigue, clinically diagnosed with periodic paralysis and supported by electrodiagnostic studies. Proband 2 is a 34-year-old woman with a history of episodic paralysis since childhood. Genetic testing in both individuals revealed potentially pathogenic variants in the MCM3AP gene. Conclusions: Periodic paralysis is a condition that significantly affects the lives of those diagnosed. The results illustrate that MCM3AP gene variants can been associated with a clinical and electrodiagnostic presentation of periodic paralysis. Additional future research should focus on clarifying any relationship between these genetic variants and the disease, as well as other possible genetic causes.