Arthroscopic Medial Meniscus Posterior Horn Direct Anchor Root Repair: Transtibial Approach With Knotless Adjustable Aperture Fixation.

The integrity of the posterior meniscus root attachment is vital for the preservation of knee joint biomechanics. Meniscus root tears treated nonoperatively or with meniscectomy lead to poor functional outcomes and progressive knee degeneration. Repair returns knee biomechanics back to the intact state and has an established record of positive mid-term to long-term results. Although transtibial pullout repair has been the gold standard, innovation is needed to overcome the limitations inherent to traditional approaches. The latest generation of transtibial pullout repair devices is adjustable, permits suture anchor placement directly into the root footprint, and has demonstrated encouraging early results in biomechanical analysis. This Technical Note describes an arthroscopic technique for medial meniscus posterior root repair that uses a knotless adjustable implant (SutureLoc; Arthrex) for aperture fixation via a transtibial approach with intratunnel soft anchor direct fixation and rip-stop suture configuration.

Quadriceps Tendon Autograft ACL Reconstruction With Suture Tape Augmentation: Safe Results Based on Minimum 2-Year Follow-up MRI.

Background: The potential intra-articular effects of ≥1 year after anterior cruciate ligament reconstruction (ACLR) with independent suture tape augmentation (STA) are not fully understood. Purpose: To investigate whether incorporating suture tape in an all-soft tissue quadriceps tendon autograft (QTA) ACLR leads to satisfactory patient outcomes while having no intra-articular side effects as determined by magnetic resonance imaging (MRI). Study Design: Case series; Level of evidence, 4. Methods: Included were 25 patients with a mean age of 19.9 years (95% CI, 17.3-22.5 years) who underwent QTA ACLR with STA between 2016 and 2019. All patients underwent MRI at ≥1 year postoperatively and had at least a 2-year follow-up (mean, 28 months [95% CI, 26.5-29.5 months]) that included physical examination with anterior laxity testing with KT-1000 arthrometer, radiographs, and patient-reported outcome measures (PROMs). At the final follow-up, the minimal clinically important difference (MCID) and the Patient Acceptable Symptom State (PASS) for applicable PROMs were applied to each patient. Postoperative graft and joint integrity were assessed using the Howell classification and the MRI Osteoarthritis Knee Score (MOAKS) joint effusion/synovitis grade. The Mann-Whitney U test for continuous variables and the chi-square or the Fisher exact test for categorical variables were used for statistical analyses. Results: The MRI assessment of the grafts demonstrated intact grafts in all patients. Overall, 96% of patients demonstrated grades 0 or 1 MOAKS for joint effusion/synovitis. All patient outcomes significantly improved from preoperatively to the final follow-up (P < .001), except for the Marx score, which decreased significantly (14.2 [95% CI, 12.7-15.8] vs 9.72 [95% CI, 7.3-12.2]; P = .0014). At least 68% of the patients achieved the MCID threshold, and 92% achieved the PASS threshold for all applicable PROMs. Conclusion: QTA ACLR with STA did not demonstrate adverse intra-articular changes on MRI at ≥1 year postoperatively. In addition, STA did not appear to negatively affect PROMs.

Primary All-Soft Tissue Quadriceps Tendon Autograft Anterior Cruciate Ligament Reconstruction With Suture Tape Augmentation Resulted in Satisfactory Patient Outcomes and a Low Graft Failure Rate in High School and Collegiate Athletes.

PURPOSE: To evaluate ≥2-year patient outcomes after primary all-soft tissue quadriceps tendon autograft (ASTQ) anterior cruciate ligament reconstruction (ACLR) with suture tape augmentation (STA) in skeletally mature high school and collegiate athletes. METHODS: All high school and collegiate athletes who underwent primary ASTQ ACLR with STA with a minimum of 2-year follow-up were analyzed retrospectively. Patients were administered validated patient-reported outcome measures (PROMs) pre- and postoperatively. The minimal clinically important difference was calculated for each PROM based on this study population and applied to the individual patient. Return to sport, subsequent surgical intervention including contralateral ACLR, and KT-1000 arthrometer measurements for knee laxity were collected. Complications were assessed by physical examination, radiologic studies, or obtained via telephone. RESULTS: In total, 60 patients were included in the final data analysis, with a mean age of 16.8 years (95% confidence interval 13-23) and mean final follow-up of 37.1 months (95% confidence interval 33.1-41.1). Twelve patients (20%) required subsequent surgery on the ipsilateral knee, which included 7 patients having a subsequent meniscal procedure and 3 patients who underwent arthrolysis. None sustained a graft failure, and 6 patients sustained a contralateral ACL injury necessitating surgery. All PROMs improved at the final follow-up (P < .001). In addition, KT-1000 arthrometer measurements significantly improved postoperatively at 1-year clinical follow-up (P < .001). Most patients obtained the minimal clinically important difference thresholds for each PROM at the final follow-up. There were 48 patients (80%) who participated in pivoting sports. The return-to-sport rate at same level was 54 patients (90%), with 6 patients (10%) not returning to the same level because of graduation. CONCLUSIONS: ASTQ ACLR with STA in a young athletic patient population may result in a low graft failure rate while maintaining satisfactory patient outcomes at short-term follow-up, including a return to sport at the same level of 90%. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Open Medial Meniscotibial Ligament Repair With Concomitant Open Superficial Medial Collateral Ligament Repair With Internal Brace Augmentation.

The medial collateral ligament (MCL) is the most commonly injured ligament in the knee. Historically, nonsurgical management for these injuries has been favored for a majority of grade I-III sprains, particularly femoral-based. However, when coupled with other injuries such as meniscotibial ligament tears or distal Stener type avulsion tears, early surgical management for these cases is recommended. This will allow for stabilization and protection of the meniscus in addition to preventing residual valgus laxity, especially related to more severe Stener-like avulsions of the superficial MCL that can be seen with meniscotibial ligament tears. Utilizing an open approach, meniscotibial repair with suture anchors with internal brace augmentation for the MCL repair can provide a strong final construct, and a safe and fast recovery.

Less Subsequent Revision Anterior Cruciate Ligament (ACL) Reconstruction Following Primary Bone-Patellar Tendon-Bone ACL Reconstruction with Suture Tape Augmentation-A Retrospective Comparative Therapeutic Trial With 5-Year Follow-up.

PURPOSE: To investigate patient outcomes, including revision rate, following primary bone patellar-tendon bone autograft (BPTB) anterior cruciate ligament reconstruction (ACLR) with and without suture tape augmentation (STA) in a young and active cohort. METHODS: All eligible patients who received primary BPTB ACLR with a minimum of 2-year follow-up were included in this retrospective cohort study. All patients receiving STA were augmented with the same device. Patients completed the following patient-reported outcome measures (PROMs): the visual analog scale, the Single Assessment Numeric Evaluation, the Knee Injury and Osteoarthritis Outcome Score subscales, and the Tegner activity scale. Anteroposterior knee laxity was assessed using a KT-1000 arthrometer preoperatively and 1-year postoperatively. Posterior tibial slope, femoral tunnel angle, and tibial tunnel placement were calculated for all patients. Subsequent surgical interventions and return to sport (RTS) were obtained from each patient. RESULTS: One hundred fourteen patients (52 BPTB ACLR with STA, 62 traditional BPTB ACLR) with a mean patient age <19 years and a mean final follow-up of ≥5 years were included. Compared with the control group, the STA group demonstrated significantly less subsequent revision ACLR (0 vs. 5, P = .036). All PROMs and KT-1000 measurements improved at final follow-up (P < .001) and were comparable between groups. There were no differences seen in either posterior tibial slope or graft tunnel placement between groups. More than 85% of the patients were able to return to the sport that led to their injury at full capacity with no differences seen in RTS rate, time to RTS, or level of competition between groups. CONCLUSIONS: Compared with traditional BPTB ACLR, additional STA appeared to safely and effectively lead to less subsequent revision ACLR while maintaining acceptable PROMs and objective joint laxity measurements in a young and active patient population. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Development and validity evidence for the resident-led large group teaching assessment instrument in the United States: a methodological study.

PURPOSE: Despite educational mandates to assess resident teaching competence, limited instruments with validity evidence exist for this purpose. Existing instruments do not allow faculty to assess resident-led teaching in a large group format or whether teaching was interactive. This study gathers validity evidence on the use of the Resident-led Large Group Teaching Assessment Instrument (Relate), an instrument used by faculty to assess resident teaching competency. Relate comprises 23 behaviors divided into six elements: learning environment, goals and objectives, content of talk, promotion of understanding and retention, session management, and closure. METHODS: Messick's unified validity framework was used for this study. Investigators used video recordings of resident-led teaching from three pediatric residency programs to develop Relate and a rater guidebook. Faculty were trained on instrument use through frame-of-reference training. Resident teaching at all sites was video-recorded during 2018-2019. Two trained faculty raters assessed each video. Descriptive statistics on performance were obtained. Validity evidence sources include: rater training effect (response process), reliability and variability (internal structure), and impact on Milestones assessment (relations to other variables). RESULTS: Forty-eight videos, from 16 residents, were analyzed. Rater training improved inter-rater reliability from 0.04 to 0.64. The Φ-coefficient reliability was 0.50. There was a significant correlation between overall Relate performance and the pediatric teaching Milestone, r = 0.34, P = .019. CONCLUSION: Relate provides validity evidence with sufficient reliability to measure resident-led large-group teaching competence.

Low Preoperative Brief Resilience Scale Scores Are Associated With Inferior Preoperative and Short-Term Postoperative Patient Outcomes Following Primary Autograft Anterior Cruciate Ligament Reconstruction.

Purpose: To assess preoperative Brief Resilience Scale (BRS) scores as they relate to postoperative patient outcomes following primary autograft anterior cruciate ligament reconstruction (ACLR). Methods: All patients who underwent primary autograft ACLR from 2016 to 2021 and had a patient-reported follow-up of 1 year and a clinical follow-up of 6 months were included in final data analysis. Patients completed validated PROMs pre- and postoperatively. All patients were objectively assessed with range of motion (ROM) and KT-1000 arthrometer testing. Return to sport (RTS) data were obtained for all applicable patients. Patients were divided into 3 groups based on ± ½ the standard deviation for the mean preoperative BRS score. Results: In total, 170 patients who underwent primary autograft ACLR with a mean age of 20.1 years (range, 13-57 years) and a mean final follow-up time of 2.9 years (range, 1.0-5.8 years) were included in the final analysis. The mean preoperative BRS scores for the high-resilience (HR, n = 67), average-resilience (AR, n = 42), and low-resilience (LR, n = 61) groups were 28.1 (95% CI, 27.8-28.9), 24.5 (95% CI, 24.3-24.6), and 21.1 (95% CI, 20.5-21.7), respectively (P < .001). The HR group demonstrated significantly higher preoperative and postoperative patient-reported outcome measures (PROMs) compared to the AR and LR groups, with more differences seen with the LR group. The HR group demonstrated better knee extension in postoperative month 3 compared to the LR group (0.6° [95% CI, -1.2° to 0.1°] vs -2.3° [95% CI, -3.3° to -1.3°], P = .006). The HR group demonstrated a faster RTS time compared to the LR group (6.4 months [95% CI, 6.1-6.7] vs 7.6 months [95% CI, 7.1-8.1], P = .002). No differences were seen in RTS rate, knee flexion, or KT-1000 arthrometer measurements between the 3 groups. Conclusions: Low preoperative BRS scores were associated with inferior PROMs preoperatively and in the short-term postoperative period compared to those with higher preoperative BRS scores. Additionally, patients with lower preoperative BRS scores demonstrated a higher degree of knee extension loss 3 months postoperatively as well as a slower RTS. Level of Evidence: Level III, retrospective cohort study.

Primary Anterior Cruciate Ligament Reconstruction with Suture Tape Augmentation: A Case Series of 252 Patients.

Anterior cruciate ligament reconstruction (ACLR) using suture tape augmentation to internally brace is a relatively new technique. The primary goal of this study was to prospectively collect patient-reported outcomes (PROs) and surgical history from patients who underwent primary ACLR with internal bracing to determine if internal bracing resulted in a low graft failure rate while maintaining acceptable PROs. A total of 252 patients with a mean age of 23.6 years (95% confidence interval [CI]: 22.1-25.1) and a mean follow-up of 37.9 months (95% CI: 35.8-40.0) were included in this study. Patients who underwent primary ACLR with internal brace augmentation between July 12, 2016 and July 31, 2021 were eligible. A total of 222 patients were contacted via telephone and administered the visual analog scale (VAS), the single assessment numeric evaluation (SANE), the Lysholm knee score scale, and, if applicable, the short version ACL return to sport after injury (SV-ACL-RSI) survey. Additionally, patients were asked to give an updated orthopaedic history. Thirty additional patients were included from either our institution's registry or by completing their surveys in-office or by e-mail. The minimal clinically important difference (MCID) and patient-acceptable symptom states (PASS) were calculated based on our patient population and applied to each individual patient. The patients' electronic health record (EHR) was searched for pre- and postoperative clinical data including KT-1000 arthrometer measurements. Two patients (0.8%) had subsequent graft failures and one patient (0.4%) required a revision surgery. MCID was achieved in 242 patients (96.0%) for the Lysholm, 227 patients (90.1%) for the SANE, and 146 patients (57.9%) for the VAS. PASS was achieved in 214 patients (84.9%) for the Lysholm, 198 patients (78.6%) for the SANE, and 199 (80.0%) patients for the VAS, postoperatively. Of note, 65 patients (25.8%) exceeded the PASS threshold for the VAS preoperatively. A total of 127 patients (84.4%) met the cutoff of ≥60/100 for the SV-ACL-RSI survey postoperatively. Postoperative KT-1000 measurements showed near-identical side-to-side differences at both the 13.6-kg pull and manual maximum pull. When stratifying patients based on age at the time of surgery, it was noted that patients younger than 25 years had significantly higher SANE scores (91.6 [95% CI: 90.2-92.9] vs. 82.6 [95% CI: 79.0-86.2]; p < 0.0001) and lower VAS pain scores (0.7 [95% CI: 0.5-0.8] vs. 1.2 [95% CI: 0.8-1.5]; p = 0.004). Primary ACLR with internal bracing led to acceptable patient outcomes and a graft failure rate of less than 1%. LEVEL OF EVIDENCE:: case series, IV.

Outcomes of Lateral Meniscal Oblique Radial Tear Repair Compared With Intact Meniscus After ACL Reconstruction: A Cohort Study.

Background: Recently, the posterior horn lateral meniscal oblique radial tear (LMORT) was identified in 12% of acute anterior cruciate ligament (ACL) injuries. However, patient-reported outcomes for repair of this relatively common tear have not been reported. Purpose: To determine the minimum 2-year functional outcomes after LMORT repair at the time of ACL reconstruction (ACLR) compared to a matched cohort of patients who underwent isolated ACLR (iACLR). Study Design: Cohort study; Level of evidence, 3. Methods: Included were 100 patients (mean age at surgery, 21 years; range, 13-45 years) who underwent primary ACLR between 2010 and 2018. The mean follow-up period was 4.1 ± 2.0 years (range, 2.0-9.2 years). A total of 50 patients with surgically repaired LMORT type 3 or type 4 lesions, defined as partial or complete tears >10 mm from the root (LMORT group) were matched 1:1 based on age, date of surgery, and graft choice with 50 patients who underwent iACLR (iACLR group). The postoperative outcomes were compared between groups using the International Knee Documentation Committee subjective score (sIKDC) and the Tegner activity scale. An updated medical history was obtained via the electronic medical record to determine any subsequent complications and reoperations. Results: There was 1 ACL graft failure in each group as well as 5 (10%) reoperations per group. None of the patients in the LMORT group necessitated a lateral meniscal revision repair or partial meniscectomy. The LMORT and iACLR groups reported comparable sIKDC scores (92.5 ± 6.8 vs 91.9 ± 8.2, respectively; P = .712) as well as Tegner scores (6.7 ± 1.8 vs 6.6 ± 1.8, respectively; P = .910) at final follow-up. No failures of the LMORT repairs were reported. Conclusion: The study findings demonstrated that reoperations, graft failure rates, patient-reported outcomes, and patient activity levels at ≥2 years after type 3 and 4 LMORT repairs at the time of ACLR compared favorably with those of a matched cohort of patients who underwent iACLR with intact meniscus.

CircRHOT1 restricts gastric cancer cell ferroptosis by epigenetically regulating GPX4.

Background: Gastric cancer (GC) is a malignant form of cancer that severely threatens human health. Despite developments on treatment, the prognosis of patients with advanced GC remains poor. Hence, the identification of detailed molecular mechanisms and potential therapeutic targets is of great importance for GC study. In recent years, circular RNAs have been widely reported to be important regulators in cancer initiation and progression. This study sought to evaluate the function of circRHOT1 in GC development. Methods: Clinical specimens were collected from patients with GC to detect the level of circRHOT1. The expression of circRHOT1 in several GC cell lines was detected by quantitative real-time polymerase chain reaction. Cell Counting Kit 8 (CCK-8), colony formation, and xenograft tumor growth experiments were performed to check cell proliferation. Cell ferroptosis was determined by the levels of intracellular iron, Fe2+ (Divalent iron ion), lipid reactive oxygen species, malondialdehyde, and glutathione. The protein levels of SLC7A11 and glutathione peroxidase-4 (GPX4) were detected by western blot assays. The epigenetic regulation of the GPX4 gene was analyzed by chromatin immunoprecipitation assays. Results: CircRHOT1 was more highly expressed in the GC tumors than the adjacent non-tumor tissues. The knockdown of circRHOT1 significantly suppressed cell growth (P<0.05) and stimulated the ferroptosis of the GC cells (P<0.05). CircRHOT1 recruited KAT5 (Acetyltransferase Tip60) to promote the acetylation of lysine 27 on histone H3 protein subunit (H3k27Ac) of the GPX4 gene and stimulated gene transcription. The overexpression of KAT5 and GPX4 notably reversed the anti-proliferation effect of circRHOT1 depletion (P<0.05). Conclusions: CircRHOT1 promoted GC progression and suppressed ferroptosis by recruiting KAT5 to initiate GPX4 transcription. Our findings showed that cirRHOT1 is a promising target for GC treatment.

Reduced Incidence of Revision Anterior Cruciate Ligament Reconstruction With Internal Brace Augmentation.

Background: Revision rates and outcome measures after anterior cruciate ligament reconstruction (ACLR) with suture tape as an internal brace is not well-documented because of the emerging nature of the technique. Hypothesis: ACLR with internal bracing (IB) would lead to decreased revision ACLR compared with traditional ACLR while exhibiting comparable patient outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 200 patients were included in this study. Patients aged between 13 and 39 years at the time of surgery who underwent primary autograft ACLR with IB between 2010 and 2020 and were enrolled in our institution's registry with a minimum of 2-year follow-up were identified and matched 1 to 1 with a non-internal brace (no-IB) group based on concomitant procedures and patient characteristics. Pre- and postoperatively, patients completed the Knee injury and Osteoarthritis Outcome Score, Marx activity rating scale, Veterans RAND 12-Item Health Survey, and visual analog scale for pain. Knee laxity measurements via the KT-1000 arthrometer were included in the pre- and postoperative objective clinical assessments. Results: A total of 100 IB patients were matched with 100 no-IB patients based primarily on concomitant procedures and secondarily on patient characteristics. The IB group underwent significantly fewer revision ACLRs (1% vs 8%; P = .017). Even though the no-IB group had a significantly longer mean final follow-up time (48.6 months [95% CI, 45.4-51.7] vs 33.4 months [95% CI, 30.3-36.5]; P < .001), the time elapsed from the original ACLR to the revision did not differ significantly between groups, and the mean ages for the IB and no-IB groups were comparable (19 vs 19.9 years). All postoperative patient-reported outcome scores between the 2 groups were comparable and significantly improved postoperatively except for the Marx score, which significantly decreased stepwise for both groups postoperatively. KT-1000 measurements significantly improved in both groups after surgery with the IB and no-IB cohorts yielding comparable results at the manual maximum pull (0.97 vs 0.65 mm). Conclusion: ACLR with IB resulted in a significantly decreased risk of revision ACLRs while maintaining comparable patient-reported outcomes. Therefore, incorporating an internal brace into ACLR appears to be safe and effective within these study parameters.

The Lateral Meniscus Oblique Radial Tear (LMORT).

PURPOSE OF REVIEW: The lateral meniscus oblique radial tear (LMORT) of the posterior horn is a relatively new term for one of the more common types of lateral meniscal tears found in patients with acute anterior cruciate ligament (ACL) injuries. Given the importance of anatomical reduction and preservation of the lateral meniscus to maintain normal knee stability and slow the progression of early-onset osteoarthritis, LMORT classification and treatment guidelines have been formulated. This article provides a review of the prevalence, classification, biomechanics, surgical repair techniques, and outcomes related to LMORT injuries. RECENT FINDINGS: Current research demonstrates favorable clinical results when LMORTs are surgically treated based on recent evidence. Biomechanically, repair of the higher grade 3 and 4 LMORT lesions have led to comparable results when compared to an intact lateral meniscus, and superior results when compared to partial meniscectomy and untreated tears. Ongoing research is aimed to determine the difference between LMORT repairs compared to intact lateral menisci at the time of ACL surgery regarding comparable patient outcomes. LMORT lesions are common tears of the lateral meniscus that should be treated surgically based on tear type at the time of ACL surgery. The benefit of doing so has already been demonstrated biomechanically.

[Successful pregnancy of a patient with primary sclerosing cholangitis awaiting liver transplantation]. / Primer szklerotizáló cholangitisben szenvedo, májtranszplantációra váró beteg sikeres várandóssága.

In women, primary sclerotising cholangitis (PSC) associated with ulcerative colitis and intrahepatic cholestasis is a rare disease. To date, there are no data from Hungary on the fertility and pregnancy outcome of women with this chronic liver disease. Our aim is to present the favorable pregnancy outcome of a woman with PSC associated with ulcerative colitis, intrahepatic cholestasis and postpartum colectomy, and review of the literature. A young nulligravida was first diagnosed with ulcerative colitis. Five years later, PSC developed with progressive fibrosis and cholestasis necessitating liver transplantation. While on waiting list, spontaneous conception occurred. Except for pregnancy-induced hypertension, pregnancy uneventfully progressed until the third trimester when 8 g oral cholestyramine/day was administered to lower high maternal (over 100 µmol/L) total bile acid (TBA) level. In the 36th week of gestation acute exacerbation of ulcerative colitis resulted in maternal fever and chorioamnionitis leading to fetal distress. Elective delivery of the eutrophic neonate followed by emergency cesarean section. In the early puerperium, colitis progressed to septic pancolitis resistant to medical treatment. 12 days after laparoscopic subtotal colectomy, the patient was discharged in good health condition. 3 months later, ileostomy was closed and she got back on the transplantation waiting list. Our data correspond with previous reports and suggest that women with PSC with underlying ulcerative colitis and cholestasis have a good chance for favorable pregnancy outcome. However, both PSC and underlying colitis might progress during pregnancy and puerperium. Oral cholestyramin is an effective and safe treatment for high maternal TBA levels. Orv Hetil. 2023; 164(6): 234-240.

Raltitrexed as a substitute for capecitabine in metastatic gastric cancer: a case report and literature review.

Background: 5-Fluorouracil and its oral prodrug, capecitabine, are frequently used in the treatment of gastrointestinal cancers-including gastric cancer-but carry a cardiotoxicity risk. Raltitrexed (brand name Tomudex), a direct inhibitor of thymidylate synthase, has been successfully used as an alternative to fluoropyrimidines in patients with 5-fluorouracil-induced cardiac events. We report the first case, to our knowledge, of raltitrexed used with trastuzumab and platinum-based chemotherapy as a substitute for fluoropyrimidines following cardiotoxicity in a 78-year-old male patient with metastatic gastric cancer. Case Description: The patient experienced a myocardial infarction 3 days after beginning treatment with capecitabine, carboplatin, and trastuzumab for metastatic HER2+ gastric adenocarcinoma. Capecitabine was replaced with raltitrexed, and the patient ultimately received seven cycles of chemotherapy, five of which included raltitrexed. There were no cardiotoxic events attributable to raltitrexed, although the patient did experience hypotensive episodes, premature ventricular contractions, myelosuppression, and anemia. Progression-free survival was 4.5 months, within the expected range achieved with the ToGA regimen (trastuzumab, cisplatin, 5-fluorouracil chemotherapy). At time of writing, the patient has been alive for 48 weeks since diagnosis. Conclusions: In summary, raltitrexed appears to be a safe alternative to fluoropyrimidines when combined with trastuzumab and platinum, although more data is needed to determine its relative effectiveness.

Extracorporeal Cytokine Removal in Critically Ill COVID-19 Patients: A Case Series.

Introduction: Extracorporeal hemoadsorption (HA) is a potential adjunctive therapy in severe cases of COVID-19 associated pneumonia. In this retrospective study we report data from critically ill patients treated with HA during the first and second wave of the pandemic. Patients and Methods: All patients, who received HA therapy with CytoSorb within the first 96 h of intensive care unit (ICU) admission without hospital-acquired bacterial superinfection, were included. Clinical and laboratory data were collected: on admission, before (TB) and after (TA) HA therapy. Results: Out of the 367 COVID-19 cases, 13 patients were treated with CytoSorb, also requiring mechanical ventilation and renal replacement therapy. All patients were alive at the end of HA, but only 3 survived hospital stay. From TB-TA there was a tendency of decreasing norepinephrine requirement: 193.7 [IQR: 34.8-270.4] to 50.2 [6.5-243.5] ug/kg/day and increasing PaO2/FiO2 ratio 127.8 (95% CI: 96.0-159.6) to 155.0 (115.3-194.6) mmHg but they did not reach statistical significance (p = 0.14 and 0.58, respectively). Treatment related adverse events were not reported. Conclusion: The treatment was well-tolerated, and there was a tendency toward an improvement in vasopressor need and oxygenation during the course of HA. These observations render the need for prospective randomized trials.

Patient-Reported Experience in the Pediatric Emergency Department: What Matters Most?

INTRODUCTION: Although the Child Hospital Consumer Assessment of Healthcare Providers and Systems is a validated tool for the inpatient experience, it may not address features unique to the pediatric emergency department (PED). There is currently no publicly available validated patient-reported experience survey for the PED, and what matters most in this setting remains unknown. METHODS: Twelve semistructured interviews were conducted with a convenience sample of parents of children younger than 14 years at a Canadian PED. Data analysis was performed using inductive thematic analysis to identify aspects of patient-reported experiences that matter most to parents in the PED. RESULTS: Five themes were identified: (1) making waiting a positive experience, (2) taking the time to provide care, (3) forging a positive partnership, (4) speak up for safe care, and (5) making the environment feel safer. Parents highlighted that while waiting for care is not desirable, it is made more acceptable through the communication of wait time estimates and the presence of child activities in the waiting room. Furthermore, although interactions with providers are brief, parents emphasized the importance of creating an environment of partnership with open communication, taking the time to examine their child, and actively demonstrating the provision of safe, quality care. CONCLUSIONS: Results from this study suggest that a patient-reported experience survey in the PED may need to embed elements not currently captured in Child Hospital Consumer Assessment of Healthcare Providers and Systems, such as waiting room experience, comprehensiveness of health assessments, and observations of safety measures. Future studies can use these findings to develop a patient-reported experience survey for use in the PED.

Mode of targeting to the proteasome determines GFP fate.

The ubiquitin-proteasome system is the canonical pathway for protein degradation in eukaryotic cells. GFP is frequently used as a reporter in proteasomal degradation assays. However, there are multiple variants of GFP in use, and these variants have different intrinsic stabilities. Further, there are multiple means by which substrates are targeted to the proteasome, and these differences could also affect the proteasome's ability to unfold and degrade substrates. Herein we investigate how the fate of GFP variants of differing intrinsic stabilities is determined by the mode of targeting to the proteasome. We compared two targeting systems: linear Ub4 degrons and the UBL domain from yeast Rad23, both of which are commonly used in degradation experiments. Surprisingly, the UBL degron allows for degradation of the most stable sGFP-containing substrates, whereas the Ub4 degron does not. Destabilizing the GFP by circular permutation allows degradation with either targeting signal, indicating that domain stability and mode of targeting combine to determine substrate fate. Difficult-to-unfold substrates are released and re-engaged multiple times, with removal of the degradation initiation region providing an alternative clipping pathway that precludes unfolding and degradation; the UBL degron favors degradation of even difficult-to-unfold substrates, whereas the Ub4 degron favors clipping. Finally, we show that the ubiquitin receptor Rpn13 is primarily responsible for the enhanced ability of the proteasome to degrade stable UBL-tagged substrates. Our results indicate that the choice of targeting method and reporter protein are critical to the design of protein degradation experiments.

Isolation and characterization of a cDNA encoding a heat shock protein 70 from a sterile mutant of Ulva pertusa (Ulvales, Chlorophyta).

Synthesis and accumulation of molecular chaperones are universal responses found in all cellular organisms when exposed to a variety of unfavorable conditions. Heat shock protein 70 (Hsp70), which is one of the major classes of molecular chaperones, plays a particularly important role in cellular stress responses, and the Hsp70 system is the most intensely studied in higher plants and algae. Therefore, we isolated and characterized a cDNA clone encoding Hsp70 from a sterile strain of Ulva pertusa (Ulvales, Chlorophyta). The sterile U. pertusa Hsp70 (UpHsp70) cDNA consisted of 2,272 nucleotides and had an open reading frame encoding a polypeptide of 663 amino acid (AA) residues with a molecular mass of 71.7 kDa. Amino acid alignment and phylogenetic analysis of Hsp70s from other organisms showed that UpHsp70 was more similar to cytoplasmic Hsp70s from green algae and higher plants (> or =75%) than to those from other algae and microorganisms. Southern blot analysis indicated that the sterile U. pertusa genome had at least four cytoplasmic Hsp70-encoding genes. UpHsp70 mRNA levels were significantly affected by diurnal changes, rapidly increased by high-temperature stress, and gradually increased by exposure to copper, cadmium, and lead. These results suggest that UpHsp70 plays particularly important roles in adaptation to high-temperature conditions and diurnal changes, and is potentially involved in tolerance to heavy metal toxicity.