bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidermal growth factor receptor inhibitor-induced diarrhea: clinical incidence, toxicological mechanism, and management
Authors: Tao Gabriel , Chityala Pavan Kumar
Published: February 2021

The epidermal growth factor receptor (EGFR) family is a class of receptor tyrosine kinase playing a central role in carcinogenesis and cancer progression. The members of this family, particularly EGFR and human epidermal growth factor receptor 2 (HER2), are the most extensively studied drug targets for malignancy. Today, numerous tyrosine kinase inhibitors targeting EGFR family have been developed to combat non-small-cell lung cancer and breast cancer. However, severe gastrointestinal (GI) toxicity leading to dose reduction and treatment discontinuation hampers the therapeutic outcome of EGFR inhibitors. Diarrhea is one of the most frequent GI side effects, especially when it comes to second-generation EGFR inhibitors. Enterocytes apoptosis and increased inflammation accompany with many oral EGFR inhibitors. Loperamide and budesonide are the first-line treatment to manage such adverse effects. However, current prophylaxis and management are all empirical interventions to relieve the symptom. They do not specifically target the toxicological mechanism of EGFR inhibitors. Hereby, those anti-diarrhea agents do not work well when used in cancer patients experiencing EGFR inhibitor-induced diarrhea. On the other hand, the toxicological mechanism of EGFR inhibitor-induced diarrhea is poorly understood. Thus, determining the mechanism behind such diarrhea is urgently in need for developing genuinely effective anti-diarrhea agents. This review aims to call attention to EGFR inhibitor-induced diarrhea, a highly occurring and devastating cancer drug toxicity.
Community-Acquired Pressure Injuries in the Acute Care Setting
Authors: Singh Charleen , Shoqirat Noordeen
Published: February 2021

OBJECTIVE

To explore the population of patients with a community-acquired pressure injury (CAPI) admitted to an acute care facility from December 2018 to December 2019. The specific aims of the study were to identify the (1) number of patients admitted with a CAPI, (2) type and frequency of pressure injury (PI), (3) location of residence prior to admission, (4) general demographics of the patient, and (5) condition of the PI at discharge.

METHODS

In this retrospective descriptive study, participants were identified and pulled from the hospital database at a 260-bed level 2 trauma center. Patients’ charts were identified by searching for nursing documentation of CAPIs. The exclusion criterion was charts that did not include verification of PI by a certified wound nurse. Data were pulled from the electronic medical record, verified by the certified wound nurse, and reviewed for participant demographics and implementation of PI prevention and treatment.

RESULTS

Over the course of the year, 88 patients had a CAPI. The majority lived at home (86.4%), were male (68.2%), and had stage 2 PIs (37%) on the sacrum (30.7%) or coccyx (51.1%). All participants had multiple comorbidities. Few PIs were from postacute care settings (11%) or another acute care hospital (1.1%). On average, patients had more than one PI. All patients had decreased or impaired mobility and mean body mass index of 26.38 ± 7.23 kg/m2. No one developed a new PI while in the acute care setting, and many of the CAPIs either healed (69.3%) or stabilized (22.7%).

CONCLUSIONS

Providers have an opportunity to make a difference in the prevalence of PIs occurring outside of acute and postacute care settings.
Postpartum Salpingectomy Compared With Standard Tubal Ligation After Vaginal Delivery
Authors: Wagar Matthew K. , Godecker Amy , Landeros Maria V. , Williams Makeba
Published: February 2021

OBJECTIVE:

To compare operative outcomes of postpartum salpingectomy and tubal ligation after vaginal delivery.

METHODS:

This retrospective cohort study identified patients who underwent tubal sterilization between January 1, 2009, and December 31, 2019, at a large academic hospital, using the electronic medical record. All patients who delivered vaginally and underwent tubal sterilization during their delivery admissions were included. The primary outcome was total operative time. Secondary outcomes included estimated blood loss, perioperative complications, and readmission within 6 weeks postpartum. Patients who underwent bilateral tubal ligation were compared with those who underwent bilateral salpingectomy using Pearson's χ2 test, Fisher exact, and Student's t test.

RESULTS:

A total of 317 eligible patients were identified. One hundred and six (94%) salpingectomies were completed using a bipolar electrocautery device. Operative time was 3 minutes shorter in the salpingectomy group, 30 minutes (interquartile range 24–38) compared with 33.5 (26–42) minutes, P=.032. Patients who underwent salpingectomy were more likely to have estimated blood loss of 5 mL or less (our institutional shorthand for minimal blood loss) than women who underwent bilateral tubal ligation (78 [69%] vs 112 [55%], P=.015). There were no significant differences in perioperative complications between the groups.

CONCLUSION:

When using electrocautery, bilateral salpingectomy can be completed in the immediate postpartum period after vaginal delivery with equivalent operative times to bilateral tubal ligation.
Surgical Outcomes After Minimally Invasive Direct Lateral Corpectomy with Percutaneous Pedicle Screws for Osteoporotic Thoracolumbar Vertebral Collapse with Neurologic Deficits in the Thoracolumbar Spine Compared with Those After Posterior Spinal Fusion with Vertebroplasty
Authors: Ohba Tetsuro , Oba Hiroki , Oda Kotaro , Tanaka Nobuki , Haro Hirotaka
Published: February 2021

Study Design.

Retrospective observational study of a cohort of consecutive patients.

Objective.

The aim of this study was to compare surgical invasion, mechanical complications, and clinical and radiological outcomes 2 years after surgery between minimally invasive corpectomy following percutaneous pedicle screw placements (X-core/PPS) and posterior fixation with vertebroplasty (VP) for treating osteoporotic vertebral fractures (OVFs), which failed conservative treatment due to neurological deficits.

Summary of Background Data.

Numerous studies have proposed surgical procedures to treat OVFs that fail conservative treatment. However, an optimal approach remains controversial because patients often have numerous comorbid medical complications, frequent instrumentation failure, and/or adjacent vertebral fracture (AVF). Recently, a minimally invasive lateral approach has attracted attention as an alternative procedure to the thoracolumbar junction for corpectomy and expandable cage replacement (X-Core Adjustable VBR System). However, its usefulness and validity is largely unknown.

Methods.

A cohort of 102 consecutive patients with OVF at T11–L1 who underwent surgery were followed up for >2 years after surgery. Ultimately 50 patients were included in the VP group and 45 in the X-core/PPS group. Surgical invasion, radiological examinations, and clinical outcomes between two procedures were compared.

Results.

Both X-core/PPS and VP procedures were safe and acceptable for neurological improvement and surgical invasion. The correction loss of local kyphotic angle (LKA) and occurrence of AVF were significantly less in the X-core/PPS group. Oswestry Disability Index in the X-core/PPS group at 2 years after surgery showed better recovery than that in the VP group, and no revision surgery was needed in the X-core/PPS group. Postoperative correction loss of LKA increased significantly when intraoperative endplate injury developed.

Conclusion.

This next-generation minimally invasive anterior and posterior combined surgery was found to be a safe and useful procedure for OVF treatment to reduce correction loss, mechanical complication, and AVF, resulting in less postoperative low back pain.

Level of Evidence: 3
Ultrasonic Bone Scalpel (USBS) Does Not Reduce Blood Loss During Posterior Spinal Fusion (PSF) in Patients with Adolescent Idiopathic Scoliosis (AIS)
Authors: Garg Sumeet , Thomas James , Darland Hannah , Kim Eun , Kittelson John , Erickson Mark , Carry Patrick
Published: February 2021

Study Design

Randomized Clinical Trial.

Objective

The aim of this study was to compare the efficacy of USBS with standard-of-care surgical instruments during posterior spinal fusion (PSF) in patients with adolescent idiopathic scoliosis (AIS) by evaluating the difference in estimated blood loss per level fused (EBL/level).

Summary of Background Data

PSF surgery for AIS is often associated with high blood loss. Use of an ultrasonic bone scalpel (USBS) has been proposed to reduce blood loss during scoliosis surgery.

Methods

This was a single-blinded (patient-blinded), randomized, controlled superiority trial. We randomized 66 patients with AIS undergoing PSF to the control group (osteotome) or the experimental group (USBS). The primary outcome was intraoperative EBL/level obtained from red blood cell salvage reports. One-year follow-up was available for 57 of 62 (92%) of patients.

Results

EBL/level averaged 35 and 39 mL/level in the experimental and control groups, respectively [adjusted mean difference USBS – osteotome −8 mL/level, 95% CI: −16.4 to 0.3 mL/level, P = 0.0575]. There was no difference in curve correction [adjusted mean difference: −1.7%, 95% CI: −7.0 to 3.6%, P = 0.5321] or operative time [adjusted mean difference: −3.55 minutes, 95% CI: −22.45 to 15.46 min, P = 0.7089] between groups. Complications requiring change in routine postoperative care were noted in eight patients: two occurred in patients assigned to the experimental group and six occurred in patients assigned to the control group.

Conclusion

There was no clinically significant difference in total blood loss, EBL/level, or complications between the two groups. In contrast to reports from other centers, at our high-volume spine center, USBS did not lead to reduced blood loss during PSF for AIS. These results may not be generalizable to centers with longer baseline operative times or higher baseline average blood loss during PSF for AIS.

Level of Evidence: 1
Assessment of the Minimum Clinically Important Difference in the Smartphone-based 6-minute Walking Test After Surgery for Lumbar Degenerative Disc Disease
Authors: Zeitlberger Anna M. , Sosnova Marketa , Ziga Michal , Regli Luca , Bozinov Oliver , Weyerbrock Astrid , Stienen Martin N. , Maldaner Nicolai
Published: February 2021

Study Design.

Prospective cohort study.

Objective.

The aim of this study was to determine the minimum clinically important difference (MCID) of the 6-minute walking test (6WT) after surgery for lumbar degenerative disc disease (DDD).

Summary of Background Data.

The smartphone-based 6WT is a valid and reliable tool to quantify objective functional impairment in patients with lumbar DDD. To date, the MCID of the 6WT has not been described in patients with DDD.

Methods.

We assessed patients pre- and 6-weeks postoperatively, analyzing both raw 6-minute walking distances (6WD; in meters) and standardized 6WT z scores. Three methods were applied to compute MCID values using established patient-reported outcomes measures (PROMs) as anchors (VAS back/leg pain, Zurich Claudication Questionnaire [ZCQ], Core Outcome Measures Index [COMI]): average change, minimum detectable change, and the change difference approach.

Result.

We studied 49 patients (59% male) with a mean age of 55.5 ± 15.8 years. The computation methods revealed MCID values ranging from 81 m (z score of 0.9) based on the VAS back pain to 99 m (z score of 1.0) based on the ZCQ physical function scale. The average MCID of the 6WT was 92 m (z score of 1.0). Based on the average MCID of raw 6WD values or standardized z scores, 53% or 49% of patients classified as 6-week responders to surgery for lumbar DDD, respectively.

Conclusion.

The MCID for the 6WT in lumbar DDD patients is variable, depending on the calculation technique. We propose a MCID of 92m (z score of 1.0), based on the average of all three methods. Using a z score as MCID allows for the standardization of clinically meaningful change and attenuates age- and sex-related differences.

Level of Evidence: 3
Fracture of the Dens Axis Due to Spinal Manifestation of Sarcoidosis
Authors: Eid Kevin , Friedrich Michael , Kudlek Claudia , Huenerlituerkoglu Ali , Schultz Johannes , Kraft Clayton N.
Published: February 2021

Study Design

Case report and literature review.

Objective

We present a case of a pathologic unstable fracture of the odontoid process due to vertebral osseous sarcoidosis. The surgical management of this unreported pathology is described and a review of the literature is given.

Summary of Background Data

Sarcoidosis is a chronic inflammatory systemic disease of unknown etiology, characterized by multiorgan noncaseating granulomatous infiltrations. It affects primarily the lungs, lymphatic system, eyes, skin, heart, and nervous system. Osseous sarcoidosis is usually clinically asymptomatic and therefore frequently under-diagnosed. When it does affect the skull or vertebral column, specific surgical therapy is only necessary in cases with nonmanageable pain or where structural integrity is threatened.

Methods

Our patient underwent a so-called semiconservative approach, consisting of a minimally invasive transoral-transpharyngeal approach, surgical debridement of the lytic bony lesion, transplantation of cancellous homologous bone, and carbon chest halo-immobilization. Halo-immobilization was left for 8 weeks, followed by a further 6 weeks with a hard cervical collar.

Results

Routine computed tomography scans 3 days, 6, 12, 18 weeks, and 1 year after surgery showed good filling of the original defect with cancellous bone, correct alignment of the upper cervical spine, and progressive fracture consolidation and stability. Surgical site infection (SSI) was not observed. The patient had no neurological postoperative deficits. After initial dysphagia, swallowing was not permanently impaired.

Conclusion

Sarcoidosis-induced odontoid fractures can be managed successfully using a semiconservative approach, consisting of transoral-transmucosal, minimally invasive surgical procedure for debridement of the lesion and transplantation of cancellous bone with additional halo-immobilization. Permanent fusion of C1-2 with loss of the cervical range of motion is avoided. Despite performing bone surgery in a potentially markedly contaminated site, bacterial infection was not an issue, possibly supported by the temporary discontinuation of immunosuppressive agents and the prudent use of antibiotics.

Level of Evidence: 4
The Association Between Leisure-time Physical Activity, Sedentary Behavior, and Low Back Pain
Authors: Lemes Ítalo Ribeiro , Pinto Rafael Zambelli , Turi Lynch Bruna Camilo , Codogno Jamile Sanches , Oliveira Crystian Bitencourt , Ross Leanna M. , Araújo Fernandes Rômulo , Monteiro Henrique Luiz
Published: February 2021

Study Design.

Observational cross-sectional.

Objective.

To investigate the association between leisure-time physical activity (LTPA) and low back pain (LBP) in adults from primary care settings, and to explore how sedentary behavior influences this association.

Summary of Background Data.

LTPA is inversely associated with LBP. However, there is no study investigating this association in primary care settings from a middle-income country. Moreover, the influence of sedentary behavior in this association is unknown.

Methods.

Cross-sectional analysis of an ongoing longitudinal study with adults from Bauru, Brazil (n = 557). Data on physical activity, sedentary behavior (sitting time), LBP, body mass index (BMI), and chronic diseases were assessed by face-to-face interviews, physical evaluation, and medical records. Binary logistic regression was used to test the association of LTPA with the presence of LBP. Sociodemographic, behavioral, and health variables were used as covariables in the multivariable models.

Results.

The fully adjusted model showed that active participants were 33% less likely to have LBP when compared with those insufficiently active (odds ratios [OR]: 0.67 [95% CI: 0.46–0.98]). A significant association was found for active participants who spent less than 3 h/day sitting (OR: 0.45 [95% CI: 0.23–0.89]) but not for those who spent 3 h/day or more in sedentary activities (OR: 0.78 [95% CI: 0.48–1.27]). An inverse association of LTPA with LBP was observed in obese participants (OR = 0.49 [95% CI: 0.25–0.94]), but not in those with normal BMI and overweight.

Conclusion.

LTPA was inversely associated with the prevalence of LBP in adults from primary care. This association was influenced by sedentary behavior and BMI.

Level of Evidence: 4
Does Patient Body Mass Index Affect the Outcome of Multimodal Rehabilitation in Chronic Mechanical Low Back Pain?
Authors: Shetty Gautam M. , Jain Shikha , Shah Nidhi , Ram C.S. , Thakur Harshad
Published: February 2021

Study Design.

Retrospective.

Objective.

The aim of this study was to investigate the effect of body mass index (BMI) on pain and disability in patients with chronic mechanical low back pain (LBP) treated with multimodal rehabilitation.

Summary of Background Data.

Despite being a well-known risk factor for developing LBP, there is minimal data on the effect of BMI on pain and disability in patients with chronic mechanical low back pain (LBP) treated with multimodal rehabilitation.

Methods.

Data from patients with chronic mechanical LBP who underwent multimodal rehabilitation treatment at a chain of spine rehabilitation outpatient clinics in one of the three BMI groups—1564 patients in normal body weight (BMI ≥18.5–24.9), 1990 patients in overweight (BMI ≥25–29.9), and 891 patients in obese (BMI ≥ 30) groups—were retrospectively analyzed. Pre- and post-treatment Numerical Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI) scores, and final treatment outcomes were compared between the three groups. Multivariate analysis was used to determine the association between pre-treatment covariates and post-treatment clinical outcomes.

Results.

Post-treatment, the mean NPRS (P = 0.005) and mean ODI (P < 0.001) scores were significantly higher with a significantly lower percentage of full success outcome (P = 0.009) in the obese group when compared to normal and overweight groups. However, multivariate analysis showed a significant correlation between age, the number of treatment sessions, pre-treatment NPRS and ODI scores, and post-treatment NPRS and ODI scores and treatment failure, and no correlation with patient BMI.

Conclusion.

Patient BMI may not affect pain and disability outcomes in patients undergoing a multimodal rehabilitation treatment for chronic LBP. In contrast to BMI, other covariates such as age, treatment sessions, and pre-treatment NPRS and ODI scores may be associated with increased risk for poor treatment outcome. Obese individuals can expect clinical outcomes similar to normal or overweight individuals with multimodal physical rehabilitation for chronic LBP.

Level of Evidence: 3
Obesity in Patients Undergoing Lumbar Degenerative Surgery—A Retrospective Cohort Study of Postoperative Outcomes
Authors: Varshneya Kunal , Wadhwa Harsh , Stienen Martin N. , Ho Allen L. , Medress Zachary A. , Aikin Jessica , Li Gordon , Desai Atman , Ratliff John K. , Veeravagu Anand
Published: February 2021

Study Design.

Retrospective cohort studying using a national, administrative database.

Objective.

The aim of this study was to determine the postoperative complications and quality outcomes of patients with and without obesity undergoing surgical management for lumbar degenerative disease (LDD).

Summary of Background Data.

Obesity is a global epidemic that negatively impacts health outcomes. Characterizing the effect of obesity on LDD surgery is important given the growing elderly obese population.

Methods.

This study identified patients with who underwent surgery for LDD between 2007 and 2016. Patients were stratified based on whether the patient had a concurrent diagnosis of obesity at time of surgery. Propensity score matching (PSM) was then utilized to mitigate intergroup differences between patients with and without obesity. Patients who underwent three or more levels surgical correction, were under the age of 18 years, or those with any previous history of trauma or tumor were excluded from this study. Baseline comorbidities, postoperative complication rates, and reoperation rates were determined.

Results.

A total of 67,215 patients underwent primary lumbar degenerative surgery, of which 22,405 (33%) were obese. After propensity score matching, baseline covariates of the two cohorts were similar. The complication rate was 8.3% in the nonobese cohort and 10.4% in the obese cohort (P < 0.0001). Patients with obesity also had longer lengths of stay (2.7 days vs. 2.4 days, P < 0.05), and higher rates of reoperation and readmission at all time-points through the study follow-up period to their nonobese counterparts (P < 0.05). Including payments after discharge, lumbar degenerative surgery in patients with obesity was associated with higher payments throughout the 2-year follow-up period ($68,061 vs. $59,068 P < 0.05).

Conclusion.

Patients with a diagnosis of obesity at time of LDD surgery are at a higher risk for postoperative complications, reoperation, and readmission.

Level of Evidence: 4
Relief of Low Back Pain After Posterior Decompression for Lumbar Spinal Stenosis
Authors: Kakiuchi Masaaki , Wada Eiji , Harada Takeo , Yamasaki Ryoji , Fukushima Wakaba
Published: February 2021

Study Design.

A retrospective study.

Objective.

The aim of this study was to confirm that decompression for lumbar spinal stenosis (LSS) relieves low back pain (LBP) as adequately as it relieves leg pain and to identify predictors for inadequate LBP relief.

Summary of Background Data.

Although decompression for LSS is generally thought to yield worse results for LBP than for leg pain, some studies have reported similar improvements in pain scores between LBP and leg pain. To treat LBP or take measures to prevent inadequate LBP relief, reliable predictors for LBP relief should be identified.

Methods.

We retrospectively reviewed 175 patients who underwent posterior element-preserving decompression and evaluated the relief of LBP and leg pain using numeric rating scales (NRSs). Associations between demographic, clinical, or imaging parameters and LBP relief at 1 and 4 years were analyzed by stepwise linear regression analyses. The imaging parameters included Modic change type 1, disc degeneration, foraminal stenosis, vertebral slipping (within Grade 1), scoliosis (<15°) and lordosis.

Results.

The mean improvements in LBP and leg pain NRS scores from baseline were 5.22 and 4.70 points (P = 0.064, paired t test) at 1 year and 5.12 and 4.62 points (P = 0.068) at 4 years, respectively. Poor LBP scores at 4 years were significantly associated with long-lasting LBP (beta = 0.31, P < 0.0001) and moderate or severe arm symptoms with cervical spinal cord compression or intramedullary hyperintense signal on T2-weighted MRI (beta = 0.22, P = 0.0014). The imaging parameters of the lumbar spine failed to show clear associations with poor LBP scores at 4 years, although Modic change type 1 showed a significant association with poor LBP scores at 1 year (beta = 0.28, P < 0.0001).

Conclusion.

Posterior decompression relieves LBP as well as leg pain. Long-lasting LBP and concurrent symptomatic cervical myelopathy are important predictors for inadequate LBP relief. There were no reliable imaging parameters predictive of inadequate LBP relief.

Level of Evidence: 4
Proximal Junctional Kyphosis Following Adolescent Idiopathic Scoliosis Correction
Authors: Ha Alex S. , Park Paul J. , Levitsky Matthew M. , Konigsberg Matthew W. , Kim Yongjung J.
Published: February 2021

Proximal junctional kyphosis (PJK) following surgical correction of adolescent idiopathic scoliosis (AIS) is a postoperative radiographic finding observed in the sagittal plane. Development of PJK has not been shown to lead to a negative clinical outcome following spinal fusion for AIS. Long-term satisfactory outcome following spinal deformity surgery is related to the status of the sagittal plane. Proper understanding and prevention of PJK in AIS surgery is needed to preserve the best sagittal plane following surgical correction of AIS.
Comparison of Mechanical Power During Adaptive Support Ventilation Versus Nonautomated Pressure-Controlled Ventilation—A Pilot Study
Authors: Buiteman-Kruizinga Laura A. , Mkadmi Hassan E. , Schultz Marcus J. , Tangkau Peter L. , van der Heiden Pim L. J.
Published: February 2021

Objectives:

The aim of this pilot study was to compare the amount of “mechanical power of ventilation” under adaptive support ventilation with nonautomated pressure-controlled ventilation.

Design:

Single-center, observational prospective pilot study adjoining unitwide implementation of adaptive support ventilation in our department.

Setting:

The ICU of a nonacademic teaching hospital in the Netherlands.

Patients:

Twenty-four passive invasively ventilated critically ill patients expected to need of invasive ventilation beyond the following calendar day.

Measurements and Main Results:

In patients under adaptive support ventilation, only positive end-expiratory pressure and Fio
2 were set by the caregivers—all other ventilator settings were under control of the ventilator; in patients under pressure-controlled ventilation, maximum airway pressure (Pmax), positive end-expiratory pressure, Fio
2, and respiratory rate were set by the caregivers. Mechanical power of ventilation was calculated three times per day. Compared with pressure-controlled ventilation, mechanical power of ventilation with adaptive support ventilation was lower (15.1 [10.5–25.7] vs 22.9 [18.7–28.8] J/min; p = 0.04). Tidal volume was not different, but Pmax (p = 0.012) and respiratory rate (p = 0.012) were lower with adaptive support ventilation.

Conclusions:

This study suggests adaptive support ventilation may have benefits compared with pressure-controlled ventilation with respect to the mechanical power of ventilation transferred from the ventilator to the respiratory system in passive invasively ventilated critically ill patients. The difference in mechanical power of ventilation is not a result of a difference in tidal volume, but the reduction in applied pressures and respiratory rate. The findings of this observational pilot study need to be confirmed in a larger, preferably randomized clinical trial.
Prior Exposure to Angiotensin II Receptor Blockers in Patients With Septic Shock to Individualize Mean Arterial Pressure Target? A Post Hoc Analysis of the Sepsis and Mean Arterial Pressure (SEPSISPAM) Trial*
Authors: Demiselle Julien , Seegers Valérie , Lemerle Marie , Meziani Ferhat , Grelon Fabien , Megarbane Bruno , Anguel Nadia , Mira Jean-Paul , Dequin Pierre-François , Gergaud Soizic , Weiss Nicolas , Legay François , Le Tulzo Yves , Conrad Marie , Robert René , Gonzalez Frédéric , Guitton Christophe , Tamion Fabienne , Tonnelier Jean-Marie , Bédos Jean-Pierre , Van Der Linden Thierry , Vieillard-Baron Antoine , Mariotte Eric , Pradel Gaël , Lesieur Olivier , Ricard Jean-Damien , Hervé Fabien , du Cheyron Damien , Guerin Claude , Teboul Jean-Louis , Helms Julie , Radermacher Peter , Asfar Pierre
Published: February 2021

OBJECTIVES:

Individualizing a target mean arterial pressure is challenging during the initial resuscitation of patients with septic shock. The Sepsis and Mean Arterial Pressure (SEPSISPAM) trial suggested that targeting high mean arterial pressure might reduce the occurrence of acute kidney injury among those included patients with a past history of chronic hypertension. We investigated whether the class of antihypertensive medications used before the ICU stay in chronic hypertensive patients was associated with the severity of acute kidney injury occurring after inclusion, according to mean arterial pressure target.

DESIGN:

Post hoc analysis of the SEPSISPAM trial.

SETTING:

The primary outcome was the occurrence of severe acute kidney injury during the ICU stay defined as kidney disease improving global outcome stage 2 or higher. Secondary outcomes were mortality at day 28 and mortality at day 90.

PATIENTS:

All patients with chronic hypertension included in SEPSISPAM with available antihypertensive medications data in the hospitalization report were included.

MEASUREMENTS AND MAIN RESULTS:

We analyzed 297 patients. Severe acute kidney injury occurred in 184 patients, without difference according to pre-ICU exposure to antihypertensive medications. Patients with pre-ICU exposure to angiotensin II receptor blockers had significantly less severe acute kidney injury in the high mean arterial pressure target group (adjusted odd ratio 0.24 with 95% CI [0.09–0.66]; p = 0.006). No statistically significant association was found after adjustment for pre-ICU exposure to antihypertensive medications and survival.

CONCLUSIONS:

Our results suggest that patients with septic shock and chronic hypertension treated with angiotensin II receptor blocker may benefit from a high mean arterial pressure target to reduce the risk of acute kidney injury occurrence.
Comparison of Sepsis Definitions as Automated Criteria
Authors: Yu Sean C. , Betthauser Kevin D. , Gupta Aditi , Lyons Patrick G. , Lai Albert M. , Kollef Marin H. , Payne Philip R. O. , Michelson Andrew P.
Published: February 2021

OBJECTIVES:

Assess the impact of heterogeneity among established sepsis criteria (Sepsis-1, Sepsis-3, Centers for Disease Control and Prevention Adult Sepsis Event, and Centers for Medicare and Medicaid severe sepsis core measure 1) through the comparison of corresponding sepsis cohorts.

DESIGN:

Retrospective analysis of data extracted from electronic health record.

SETTING:

Single, tertiary-care center in St. Louis, MO.

PATIENTS:

Adult, nonsurgical inpatients admitted between January 1, 2012, and January 6, 2018.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

In the electronic health record data, 286,759 encounters met inclusion criteria across the study period. Application of established sepsis criteria yielded cohorts varying in prevalence: Centers for Disease Control and Prevention Adult Sepsis Event (4.4%), Centers for Medicare and Medicaid severe sepsis core measure 1 (4.8%), International Classification of Disease code (7.2%), Sepsis-3 (7.5%), and Sepsis-1 (11.3%). Between the two modern established criteria, Sepsis-3 (n = 21,550) and Centers for Disease Control and Prevention Adult Sepsis Event (n = 12,494), the size of the overlap was 7,763. The sepsis cohorts also varied in time from admission to sepsis onset (hr): Sepsis-1 (2.9), Sepsis-3 (4.1), Centers for Disease Control and Prevention Adult Sepsis Event (4.6), and Centers for Medicare and Medicaid severe sepsis core measure 1 (7.6); sepsis discharge International Classification of Disease code rate: Sepsis-1 (37.4%), Sepsis-3 (40.1%), Centers for Medicare and Medicaid severe sepsis core measure 1 (48.5%), and Centers for Disease Control and Prevention Adult Sepsis Event (54.5%); and inhospital mortality rate: Sepsis-1 (13.6%), Sepsis-3 (18.8%), International Classification of Disease code (20.4%), Centers for Medicare and Medicaid severe sepsis core measure 1 (22.5%), and Centers for Disease Control and Prevention Adult Sepsis Event (24.1%).

CONCLUSIONS:

The application of commonly used sepsis definitions on a single population produced sepsis cohorts with low agreement, significantly different baseline demographics, and clinical outcomes.
The Lived Experience of ICU Clinicians During the Coronavirus Disease 2019 Outbreak: A Qualitative Study
Authors: Kentish-Barnes Nancy , Morin Lucas , Cohen-Solal Zoé , Cariou Alain , Demoule Alexandre , Azoulay Elie
Published: February 2021

OBJECTIVES:

During the coronavirus disease 2019 pandemic, frontline healthcare professionals were asked to reorganize the provision of critical care in unprecedented ways. Our aim was to gain insight into the lived experience of clinicians who worked in ICUs during the surge.

DESIGN:

Qualitative study using semistructured, in-depth interviews.

SETTING:

Clinicians who worked in three ICUs in Paris (France) during the peak of the pandemic (April and May 2020).

Participants:

Twenty-seven ICU clinicians (12 physicians, 11 nurses, three nursing assistants, and one respiratory therapist).

MEASUREMENTS AND MAIN RESULTS:

Interviews were audio recorded and analyzed using thematic analysis. Six themes emerged: coping with initial disorganization and creating new routines, the intensification of professional relationships and the development of unexpected collaborations, losing one’s reference points and recreating meaningful interactions with patients, working under new constraints and developing novel interactions with family members, compensating for the absence of family members and rituals at the end of life, and the full engagement of ICU clinicians during the coronavirus disease 2019 crisis.

CONCLUSIONS:

Among ICU clinicians, there was a sense of total professional engagement during the surge. Caring for critically ill coronavirus disease 2019 patients was fraught with challenges and generated a strong feeling of responsibility, as clinicians felt they had to compensate for the absence of family members. Rethinking policies about family visits and safeguarding positive relationships among colleagues are two important priorities for future healthcare crises.
Acute Axonal Motor Neuropathy With Completely Reversible Conduction Failure—Is It Really Axonal?
Authors: Carneiro Fábio , Sequeira João , Goulart Zulmira , Pereira Pedro
Published: February 2021

We present the case of a 24-year-old man with a 3-day history of limb weakness and flaccid tetraparesis, hyporreflexia, and gait difficulties (Hughes grade 3) in the examination. Electromyography at presentation revealed severe amplitude reduction in distal compound muscle action potentials of several nerves without features of demyelination, fulfilling electrodiagnostic criteria for acute axonal motor neuropathy. The patient was treated with immunoglobulin and recovered completely 21 days after symptom onset. Electromyography at this timepoint showed normalization of compound muscle action potentials without increased temporal dispersion. The electroclinical recovery profile in this patient is consistent with reversible conduction failure in distal nerve segments in detriment of axonal degeneration. Thus, it is an “axonal motor neuropathy” where axonopathy is unlikely, giving strength to the concept of “nodopathies/paranodopathies.”
Improving Emergency Cricothyroidotomies
Authors: Clark Clayton M. , Morgan Brett T. , Schmitt Daniel , Harman Robert J. , Goode Victoria
Published: February 2021

This article discusses skill proficiency of providers related to emergency cricothyroidotomies. Various techniques to improve procedural skills were studied. Accurate identification of the cricothyroid membrane via palpation remained consistently inadequate. High-fidelity simulation including the use of human cadavers may be the preferred method of skill training for crisis management. The authors emphasize that additional research is needed regarding a method for rapid cricothyroid membrane identification as well as needle cricothyroidotomy versus surgical airway on cadavers. More consistent training will enable emergency care providers to perform this rare but lifesaving skill.
End-of-Life Care
Authors: Myers Joan Carr , Hyrkas Kristiina
Published: February 2021

This quality improvement initiative originated in the cardiac intensive care unit (CICU) at a 637-bed licensed Magnet teaching hospital with the rating of level 1 trauma center. The CICU has 12 beds, with a staff of 59 nurses (RNs). The nursing staff expressed increased stress and discomfort when communicating with patients and their families when providing end-of-life care. Selected evidence-based techniques for stress reduction and active listening skills were taught in 4- to 5-minute mini sessions during the morning huddle 3 days per week for 4 weeks. The program was evaluated using pretest, posttest, and 2 follow-up surveys composed of 5 statements and 2 open-ended questions. The survey tool was developed by researchers in accordance with the relevant literature. The results showed improved communication as demonstrated by the surveys. Nurses also reported feeling more supported by their colleagues and supervisors. The project was conducted in 1 CICU, therefore limiting the generalizability of the results.
Tetracyclines, a promise for neuropsychiatric disorders: from adjunctive therapy to the discovery of new targets for rational drug design in psychiatry
Authors: Chaves Filho Adriano José Maia , Mottin Melina , Soares Michele Verde-Ramo , Jucá Paloma Marinho , Andrade Carolina Horta , Macedo Danielle S.
Published: February 2021

Major mental disorders, such as schizophrenia, bipolar disorder, and major depressive disorder, represent the leading cause of disability worldwide. Nevertheless, the current pharmacotherapy has several limitations, and a large portion of patients do not respond appropriately to it or remain with disabling symptoms overtime. Traditionally, pharmacological interventions for psychiatric disorders modulate dysfunctional neurotransmitter systems. In the last decades, compelling evidence has advocated for chronic inflammatory mechanisms underlying these disorders. Therefore, the repurposing of anti-inflammatory agents has emerged as an attractive therapeutic tool for mental disorders. Minocycline (MINO) and doxycycline (DOXY) are semisynthetic second-generation tetracyclines with neuroprotective and anti-inflammatory properties. More recently, the most promising results obtained in clinical trials using tetracyclines for major psychiatric disorders were for schizophrenia. In a reverse translational approach, tetracyclines inhibit microglial reactivity and toxic inflammation by mechanisms related to the inhibition of nuclear factor kappa B signaling, cyclooxygenase 2, and matrix metalloproteinases. However, the molecular mechanism underlying the effects of these tetracyclines is not fully understood. Therefore, the present review sought to summarize the latest findings of MINO and DOXY use for major psychiatric disorders and present the possible targets to their molecular and behavioral effects. In conclusion, tetracyclines hold great promise as (ready-to-use) agents for being used as adjunctive therapy for human neuropsychiatric disorders. Hence, the understanding of their molecular mechanisms may contribute to the discovery of new targets for the rational drug design of novel psychoactive agents.
Valproate selectively suppresses adolescent anabolic/androgenic steroid-induced aggressive behavior: implications for a role of hypothalamic γ-aminobutyric acid neural signaling
Authors: Lee Terrence J. , Zanello Andrea F. , Morrison Thomas R. , Ricci Lesley A. , Melloni Richard H.
Published: February 2021

Pubertal male Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids (AASs) during adolescence (P27–P56) display a highly intense aggressive phenotype that shares many behavioral similarities with pathological aggression in youth. Anticonvulsant drugs like valproate that enhance the activity of the γ-aminobutyric acid (GABA) neural system in the brain have recently gained acceptance as a primary treatment for pathological aggression. This study examined whether valproate would selectively suppress adolescent AAS-induced aggressive behavior and whether GABA neural signaling through GABAA subtype receptors in the latero-anterior hypothalamus (LAH; an area of convergence for developmental and neuroplastic changes that underlie aggression in hamsters) modulate the aggression-suppressing effect of this anticonvulsant medication. Valproate (1.0–10.0 mg/kg, intraperitoneal) selectively suppressed the aggressive phenotype in a dose-dependent fashion, with the effective anti-aggressive effects beginning at 5 mg/kg, intraperitoneally. Microinfusion of the GABAA receptor antagonist bicuculline (7.0–700 ng) into the LAH reversed valproate’s suppression of AAS-induced aggression in a dose-dependent fashion. At the 70 ng dose of bicuculline, animals expressed the highly aggressive baseline phenotype normally observed in AAS-treated animals. These studies provide preclinical evidence that the anticonvulsant valproate selectively suppresses adolescent, AAS-induced aggression and that this suppression is modulated, in part, by GABA neural signaling within the LAH.
Behavioral pharmacology of five novel synthetic cannabinoids
Authors: Gatch Michael B. , Tourigny Andrew , Shetty Ritu A. , Forster Michael J.
Published: February 2021

Newly emerging synthetic cannabinoid compounds continue to be found in the designer drug market. They are often targeted as a ‘legal high’ alternative to traditional cannabinoids via ‘darknet’ markets and their increased potency and efficacy are becoming a growing concern internationally. The purpose of this study was to determine whether 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-AEB, 5F-CUMYL-P7AICA and EMB-FUBINACA exhibited similar behavioral effects as Δ9-tetrahydrocannabinol (Δ9-THC). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Male Sprague-Dawley rats were trained to discriminate between intraperitoneal injections of Δ9-THC (3 mg/kg) and vehicle. Following successful training, substitution tests for 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-AEB, 5F-CUMYL-P7AICA and EMB-FUBINACA were conducted. All of the test compounds decreased locomotor activity. 4-CN-CUMYL-BUTINACA (ED50 = 0.26 mg/kg), 4F-MDMB-BINACA (ED50 = 0.019 mg/kg), 5F-CUMYL-P7AICA (ED50 = 0.13 mg/kg) and EMB-FUBINACA (ED50 = 0.13 mg/kg) each fully substituted for the discriminative stimulus effects of the training dose of Δ9-THC, whereas 5F-AEB produced only a maximum of 67% drug-appropriate responding at 0.5 mg/kg. Higher doses produced piloerection, exophthalmos and convulsions. 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-CUMYL-P7AICA and EMB-FUBINACA are likely to produce similar subjective effects in humans as those produced by abused synthetic cannabinoids, and may therefore share similar abuse liability. In contrast, 5F-AEB may have a reduced abuse liability given its weaker THC-like discriminative stimulus effects but maybe more dangerous due to the adverse effects observed at doses needed to produce discriminative stimulus effects.
Treatment of Iatrogenic Saphenous Neuroma after Knee Arthroscopy with Excision and Allograft Reconstruction
Authors: Schur Mathew D. , Sochol Kristen M. , Lefebvre Rachel , Stevanovic Milan
Published: February 2021

Background:

The treatment of postoperative, painful sensory neuromas is an ongoing challenge for surgeons. Here, we describe a technique for treatment with excision and allograft reconstruction and report on early results of its use in treating painful saphenous neuromas after knee arthroscopy.

Methods:

A retrospective review of a single surgeon’s peripheral nerve clinic from January 1, 2013, to December 31, 2019, was conducted to identify post-knee arthroscopy saphenous neuroma cases in which reconstruction with processed human nerve allograft distally implanted into healthy muscle belly was performed. We examined the outcomes for each patient, including subjective pain self-assessment and need for further surgical treatment.

Results:

In total, 9 cases were identified, with patient ages ranging from 21 to 74 years. The average time to referral to peripheral nerve clinic was 31 months (range: 4–143 months). Upon exploration, all nerves were found to have a neuroma in continuity. Six of the 9 patients reported subjective improvement through final follow-up. Three of the 9 patients reported initial improvement, with recurrence of pain at/near the site of the neuroma. The average follow-up time was 9 months (range: 1–21 months).

Conclusions:

Here, we report on a novel technique of using a processed human nerve allograft after neuroma resection to provide an organized environment for bridging regenerated axons into muscle tissue. We also describe our early results using this technique to treat iatrogenic saphenous neuromas after knee arthroscopy. Results are encouraging, with 6 of the 9 patients experiencing subjective reduction in pain at final follow-up.
Wound Healing of Descemet Membrane After Penetrating Keratoplasty and Its Relevance for Descemet Membrane Endothelial Keratoplasty Surgeons
Authors: Steindor Friedrich A. , Clemens Amelie C. , Herwig-Carl Martina C. , Loeffler Karin U. , Menzel-Severing Johannes , Geerling Gerd
Published: February 2021

Compared with penetrating keratoplasty (PK), Descemet membrane endothelial keratoplasty (DMEK) is characterized as lower risk for complications such as immunological graft reaction and faster and better postoperative visual recovery. In patients with endothelial graft failure after PK, DMEK can be used to regenerate PK graft transparency. The surgical technique for DMEK in this specific situation is still under debate, particularly regarding stripping of Descemet membrane (DM) from the failed PK and diameter of the DMEK graft. Here we report a case of a 75-year-old female patient with a failed graft 16 years after PK for Fuchs endothelial dystrophy, who underwent uneventful DMEK surgery. Stripping of DM in this particular case was performed outside the failed PK and demonstrated a biomechanically stable junction between the PK donor and the host DM. Histopathologic analysis of the excised DM showed continuous extracellular matrix connecting the host and donor DM, indicating primary intention wound healing after PK at this tissue level. This case demonstrates that after PK, a biomechanically stable and histologically continuous DM can enable Descemetorhexis outside the failed graft and transplantation of a DMEK graft larger than the previous PK. This may provide more endothelial cells for transplantation.
Indocyanine Green Angiographic Assessment of Conjunctival Melanocytic Disorders
Authors: Palme Christoph , Wanner Astrid , Romano Vito , Franchi Alexander , Haas Gertrud , Kaye Stephen B. , Steger Bernhard
Published: February 2021

Purpose:

To investigate whether transvascular indocyanine green (ICG) dye leakage is associated with conjunctival malignancy.

Methods:

This is a prospective interventional study. Patients presenting with circumscribed conjunctival melanocytic disorders (CMDs) were included and examined using color photography, anterior segment optical coherence tomography to measure lesion size, and fluorescein and ICG angiography to measure vascular pattern and leakage. Time to vascular leakage was measured by 2 independent observers. Lesions were characterized as benign or malignant based on histopathological features.

Results:

Thirty patients with CMD were included: 22 lesions were benign (conjunctival nevus, n = 20; conjunctival melanocytic intraepithelial neoplasia without atypia, n = 2) and 8 were malignant (in situ conjunctival melanoma n = 2; invasive conjunctival melanoma, n = 6). Malignant lesions had larger mean maximal diameters (11.0 ± 4.5 vs. 4.2 ± 2.5 mm, P = 0.003) and more frequently showed intrinsic tumor vasculature (8 of 8 vs. 10 of 22, P = 0.007). The mean time to ICG leakage was 350.9 ± 165.9 seconds in benign and 59.6 ± 22.1 seconds (P = 0.002) in malignant lesions and was inversely correlated with lesion size and thickness.

Conclusions:

Time to angiographic ICG dye leakage is significantly shorter in malignant versus benign CMD.