Single-centre review of the management of intra-thoracic oesophageal perforation in a tertiary oesophageal unit: paradigm shift, short- and long-term outcomes over 15 years.

BACKGROUND: Oesophageal perforation is an uncommon surgical emergency associated with high morbidity and mortality. The timing and type of intervention is crucial and there has been a major paradigm shift towards minimal invasive management over the last 15 years. Herein, we review our management of spontaneous and iatrogenic oesophageal perforations and assess the short- and long-term outcomes. METHODS: We performed a retrospective review of consecutive patients presenting with intra-thoracic oesophageal perforation between January 2004 and Dec 2020 in a single tertiary hospital. RESULTS: Seventy-four patients were identified with oesophageal perforations: 58.1% were male; mean age of 68.28 ± 13.67 years. Aetiology was spontaneous in 42 (56.76%), iatrogenic in 29 (39.2%) and foreign body ingestion/related to trauma in 3 (4.1%). The diagnosis was delayed in 29 (39.2%) cases for longer than 24 h. There was change in the primary diagnostic modality over the period of this study with CT being used for diagnosis for 19 of 20 patients (95%). Initial management of the oesophageal perforation included a surgical intervention in 34 [45.9%; primary closure in 28 (37.8%), resection in 6 (8.1%)], endoscopic stenting in 18 (24.3%) and conservative management in 22 (29.7%) patients. On multivariate analysis, there was an effect of pathology (malignant vs. benign; p = 0.003) and surgical treatment as first line (p = 0.048) on 90-day mortality. However, at 1-year and overall follow-up, time to presentation (≤ 24 h vs. > 24 h) remained the only significant variable (p = 0.017 & p = 0.02, respectively). CONCLUSION: Oesophageal perforation remains a condition with high mortality. The paradigm shift in our tertiary unit suggests the more liberal use of CT to establish an earlier diagnosis and a higher rate of oesophageal stenting as a primary management option for iatrogenic perforations. Time to diagnosis and management continues to be the most critical variable in the overall outcome.

SPEG (Striated Muscle Preferentially Expressed Protein Kinase) Is Essential for Cardiac Function by Regulating Junctional Membrane Complex Activity.

RATIONALE: Junctional membrane complexes (JMCs) in myocytes are critical microdomains, in which excitation-contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction in failing hearts. However, the role of newly identified JMC protein SPEG (striated muscle preferentially expressed protein kinase) remains unclear. OBJECTIVE: To determine the role of SPEG in healthy and failing adult hearts. METHODS AND RESULTS: Proteomic analysis of immunoprecipitated JMC proteins ryanodine receptor type 2 and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine-threonine kinase SPEG as the only novel binding partner for both proteins. Real-time polymerase chain reaction revealed the downregulation of SPEG mRNA levels in failing human hearts. A novel cardiac myocyte-specific Speg conditional knockout (MCM-Spegfl/fl) model revealed that adult-onset SPEG deficiency results in heart failure (HF). Calcium (Ca2+) and transverse-tubule imaging of ventricular myocytes from MCM-Spegfl/fl mice post HF revealed both increased sarcoplasmic reticulum Ca2+ spark frequency and disrupted JMC integrity. Additional studies revealed that transverse-tubule disruption precedes the development of HF development in MCM-Spegfl/fl mice. Although total JPH2 levels were unaltered, JPH2 phosphorylation levels were found to be reduced in MCM-Spegfl/fl mice, suggesting that loss of SPEG phosphorylation of JPH2 led to transverse-tubule disruption, a precursor of HF development in SPEG-deficient mice. CONCLUSIONS: The novel JMC protein SPEG is downregulated in human failing hearts. Acute loss of SPEG in mouse hearts causes JPH2 dephosphorylation and transverse-tubule loss associated with downstream Ca2+ mishandling leading to HF. Our study suggests that SPEG could be a novel target for the treatment of HF.

A developmental view of mentoring talented students in academic and nonacademic domains.

The role of mentors for talented students varies according to developmental level and domain. Domains differ as to when they begin, peak, and end. Therefore, mentoring at the beginning of a talent trajectory may take place in middle school for a science student and in elementary school for a violinist. In the later stages of talent development, mentors are more likely to select their protégés than to be organizationally matched with mentees. As mentees gain the requisite skills and knowledge, mentors place more emphasis on modeling and coaching for psychosocial skills and insider knowledge (access to networks of information, attitudes, and behaviors rewarded by gatekeepers) that allow their mentees to stand out and, if necessary, endure pushback derived from proposing creative ideas or performances that challenge the status quo. The conclusions reported here are derived from studies of mentoring talented students, with an emphasis on identifying similarities across domains, and recognition that mentors' provision of insider knowledge is particularly important for low-income children and youth.

Necrotizing Fasciitis: Expect the unexpected.

INTRODUCTION: Necrotizing fasciitis is a rapidly progressive and potentially fatal soft tissue infection. A wide spectrum of aerobic and nonaerobic organisms has been implicated as the causative pathogen. Necrotizing Fasciitis due to Salmonella serovars have previously been implicated both with and without a prodromal diarrheal illness, but mono-microbial Salmonella NF is very rare. CASE PRESENTATION: We have discussed the case of a 67-year-old man who presented with necrotizing fasciitis of the perianal region in the emergency department of our hospital. He underwent serial debridement and a defunctioning colostomy, tissue and blood cultures revealed Salmonella Newport as the culprit microorganism. He received antibiotic therapy tailored to the organism and was discharged on recovery. He currently awaits a reversal of his colostomy. DISCUSSION: Necrotizing fasciitis infections are rapidly progressive and potentially lethal, a high index of suspicion and aggressive surgical debridement supplemented with culture sensitive antibiotics is essential. Salmonella Newport has recently been implicated in diarrheal illness, associated with consumption of minced beef in the US. To the best of our knowledge, no previous reports of NF have been published related to Salmonella newport. The unexpected growth of this organism from tissue cultures and the excellent response to treatment prompted us to highlight this case as the first report of its type in the medical literature. CONCLUSION: Necrotizing soft tissue infections are associated with considerable morbidity and mortality, and delayed recognition and treatment can have severe implications. Necrotizing fasciitis due to Salmonella serovars has been reported with Group B and C however no previous reports of NF have been reported with this serovar.