Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Arterial embolization of retained kidney remnant following blunt traumatic injury: A case report

Introduction: There has been a recent trend toward nonoperative management of solid organ injuries with arteriography and embolization as alternatives to surgical exploration. We examine the use of arterial embolization in the management of a post-subtotal nephrectomy urinoma in a patient with severe renal injury secondary to blunt trauma. Methods: This case report has been reported in line with the CARE criteria [13]. Presentation of case: A 35-year-old female patient presented with a persistent urinoma after an incomplete nephrectomy for blunt renal trauma. Computed tomography scan of the abdomen demonstrated a 47 × 68 × 101 mm3 collection superior to the remnant of the resected right kidney. With persistence of the urinoma after placement of an 8 French drainage catheter, the patient was taken for arterial embolization of the lower renal artery for ablation of the kidney remnant. Discussion: Most kidney injuries with urinoma formation are treated successfully with supportive measures, however refractory cases require intervention. Arterial embolization has been used successfully in the treatment of traumatic pseudoaneurysms, arteriovenous fistulas, and some renal tumors. In this patient, we extended the use of embolization to infarct vessels of the functioning kidney remnant as an alternative to surgery. Post-embolization the patient recovered well with permanent resolution of the urinoma and short-term side effects limited to short-lived fever and lumbar pain. Conclusion: Arterial embolization should be considered as an alternative to surgery in cases of persistent urinoma following renal trauma with retained remnants

A Fast-track Pathway for Emergency General Surgery at an Academic Medical Center

BACKGROUND: Fast Track Pathways (FTP) directed at reducing length of stay (LOS) and overall costs are being increasingly implemented for emergency surgeries. The purpose of this study is to evaluate implementation of a FTP for Emergency General Surgery (EGS) at an academic medical center (AMC). METHODS: The study included 165 patients at an AMC between 2016 and 2018 who underwent laparoscopic appendectomy (LA), laparoscopic cholecystectomy (LC), or laparoscopic inguinal hernia repair (LI). The FTP group enrolled 89 patients, and 76 controls prior to FTP implementation were evaluated. Time to surgery (TTS), LOS, and post-operative LOS between groups were compared. Direct costs, reimbursements, and patient reported satisfaction (satisfaction 1 = never, 4 = always) were also studied. RESULTS: The sample was 60.6% female, with a median age of 40 years. Case distribution differed slightly (56.2% versus 42.1% LA, 40.4% versus 57.9% LC, FTP versus control), but TTS was similar between groups (11h39min versus 10h02min, P = 0.633). LOS was significantly shorter in the FTP group (15h17min versus 29h09min, P \u3c 0.001), reflected by shorter post-operative LOS (3h11min versus 20h10min, P \u3c 0.001), fewer patients requiring a hospital bed and overnight stay (P \u3c 0.001). Direct costs were significantly lower in the FTP group, reimbursements were similar (P \u3c 0.001 and P = 0.999 respectively), and average patient reported satisfaction was good (3.3/4). CONCLUSION: In an era focused on decreasing cost, optimizing resources, and ensuring patient satisfaction, a FTP can play a significant role in EGS. At an AMC, an EGS FTP significantly decreased LOS, hospital bed utilization while not impacting reimbursement or patient satisfaction

Operational Regimes in Picosecond and Femtosecond Pulse-Excited Ultrahigh Vacuum SERS

We report a systematic study performed in ultrahigh vacuum designed to identify the laser excitation regimes in which plasmonically enhanced ultrashort pulses may be used to nondestructively probe surface-bound molecules. A nondestructive, continuous-wave spectroscopic probe is used to monitor the effects of four different femtosecond- and picosecond-pulsed beams on the SER signals emanating from molecular analytes residing within plasmonically enhanced fields. We identify the roles of plasmonic amplification and alignment with a molecular electronic transition on the observed changes in the SER signals. Our results indicate that overlap of the laser wavelength with the plasmon resonance is the dominant contributor to signal degradation. In addition, signal loss for a given irradiation condition is observed only for molecules residing in hot spots above a threshold enhancement. Identification of suitable laser energy density ranges demonstrates the importance of considering these parameters when implementing SERS in the presence of pulsed irradiation

A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears.

BACKGROUND: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation. MATERIALS AND METHODS: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome. MicroRNA targets were predicted using messenger RNA (mRNA) transcripts from black bear kidney cells. In vitro studies were performed to confirm the relationship between identified microRNAs and mRNA expression, using artificial microRNA and human liver cells. RESULTS: Using the bear genome, we identified 15 microRNAs differentially expressed in the plasma of hibernating black bears. Of these microRNAs, three were significantly downregulated (miR-141-3p, miR-200a-3p, and miR-200c-3p), were predicted to target SERPINC1, the gene for antithrombin, and demonstrated regulatory control of the gene mRNA expression in cell studies. CONCLUSIONS: Our findings suggest that the hibernating black bears\u27 ability to maintain hemostasis and achieve protection from venous thromboembolism during prolonged periods of immobility may be due to changes in microRNA signatures and possible upregulation of antithrombin expression