bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized ß-lactam dosing in patients with coronavirus disease 2019 (COVID-19) and pneumonia
Authors: Chiriac Ute , Frey Otto R. , Roehr Anka C. , Koeberer Andreas , Gronau Patrick , Fuchs Thomas , Roberts Jason A. , Brinkmann Alexander
Published: June 2021

Pathophysiological changes are important risk factors for critically ill patients with pneumonia manifesting sub-therapeutic antibiotic exposures during empirical treatment. The effect of coronavirus disease 2019 (COVID-19) on antibiotic dosing requirements is uncertain. We aimed to determine the effect of COVID-19 on ß-lactam pharmacokinetics (PK) and PK target attainment in critically ill patients with a personalized dosing strategy.

Retrospective, single-center analysis of COVID-19 ± critically ill patients with pneumonia (community-acquired pneumonia or hospital-acquired pneumonia) who received continuous infusion of a ß-lactam antibiotic with dosing personalized through dosing software and therapeutic drug monitoring. A therapeutic exposure was defined as serum concentration between (css) 4 to 8 times the EUCAST non-species related breakpoint).

Data from 58 patients with pneumonia was analyzed. Nineteen patients were tested COVID-19-positive before the start of the antibiotic therapy for community-acquired pneumonia or hospital-acquired pneumonia. Therapeutic exposure was achieved in 71% of COVID-19 patients (68% considering all patients). All patients demonstrated css above the non–species-related breakpoint. Twenty percent exceeded css above the target range (24% of all patients). The median ß-lactam clearance was 49% compared to ß-lactam clearance in a standard patient without a significant difference regarding antibiotic, time of sampling or present COVID-19 infection. Median daily doses were 50% lower compared to standard bolus dosing.

COVID-19 did not significantly affect ß-lactam pharmacokinetics in critically ill patients. Personalized ß-lactam dosing strategies were safe in critically ill patients and lead to high PK target attainment with less resources.
Insulin immunotherapy for pretype 1 diabetes
Authors: Jacobsen Laura M. , Schatz Desmond A.
Published: June 2021

Purpose of review

Loss of tolerance to insulin likely contributes to the immunopathogenesis of type 1 diabetes (T1D). Several large clinical trials and smaller mechanistic studies have failed to demonstrate the efficacy of insulin antigen therapy. The growing awareness of the heterogeneity of T1D likely affects the response to various immune therapies including insulin. Identification of biomarkers of clinical response will provide further insight into mechanisms leading to the disease and classify responders in the quest for personalized therapy.

Recent findings

Several biomarkers have identified subpopulations in posthoc analyses that showed benefit from oral insulin even though the placebo-controlled study was as a whole unsuccessful. High insulin autoantibody titer, low first phase insulin response, and high Diabetes Prevention Trial-Type 1 Risk Score identify at-risk relatives more likely to benefit from oral insulin. Future incorporation of human leukocyte antigen and the variable number of tandem repeats polymorphism located in the insulin gene promoter (INS VNTR) is of interest for both primary and secondary prevention studies.

Although primary and secondary prevention trials using oral insulin are ongoing, those completed have been largely unsuccessful. However, we believe that oral insulin should be considered in future trials as part of combination therapies as prerandomization biomarker testing is refined.
Fibrosis scores that can be used in follow-up of after direct-acting antiviral treatment: APRI, FIB-4, King score and GUCI
Authors: Tahtasakal Ceren Atasoy , Oncul Ahsen , Sevgi Dilek Yildiz , Demirbas Duygu , Gunduz Alper , Dokmetas Ilyas
Published: June 2021

Introduction

Sustained virologic response in the treatment of chronic hepatitis C can be achieved with direct-acting antivirals (DAA) in recent years. Monitoring virologic and histologic response to treatment is essential and noninvasive methods are preferred. In our study, we aimed to determine the regression of fibrosis following DAA treatment with serum fibrosis indices constituting a noninvasive method.

Method

Patients with chronic hepatitis C to whom DAA treatment is started between January 2016 and January 2018 in our clinic are evaluated retrospectively. The fibrosis scores [fibrosis 4 index (FIB-4), aminotransferase platelet ratio (APRI), Fibro QKing score, age platelet index, Goteburg University Cirrhosis Index (GUCI), aspartate transaminase/alanine transaminase ratio (AAR)] are calculated with routine biochemical and hematologic tests of DAA-treated patients before treatment, at the end of treatment, and in the 12th and 24th weeks of treatment. In total, the course of seven scores calculated at four separate times including baseline was recorded and compared.

Results

In total 91 patients are included in the study. The average age was 51.16 ± 13.78 and 59.3% (n = 54) of patients were women. According to the baseline FIB-4 values, the patients were grouped as cirrhotic or noncirrhotic, and 11 of them were cirrhotic (12.1%). Statistically significant regression in APRI, FIB-4, GUCI and King scores is seen in all groups regardless of their cirrhotic status, treatment experience or genotype (P < 0.001). Specified scores had a positive, significant correlation with pretreatment biopsy results [area under curve (AUC): 0.800, 0.782, 0.749 and 0.746].

Conclusion:

APRI, FIB-4, GUCI and King scores that have a positive correlation with biopsy can also be used for fibrosis recovery follow-up after treatment with DAAs.
Short-term clinical outcomes of non-curative endoscopic submucosal dissection for early esophageal adenocarcinoma
Authors: Othman Mohamed O , Bahdi Firas , Ahmed Yahya , Gagneja Harish , Andrawes Sherif , Groth Shawn , Dhingra Sadhna
Published: June 2021

Objectives

Few Western studies highlighted the outcomes of endoscopic submucosal dissection (ESD) for early esophageal adenocarcinoma (EAC). Data regarding the outcomes of noncurative ESDs remains scarce. In this study, we share our experience with ESD for early EAC with a focus on noncurative ESDs.

Methods

A retrospective single-center analysis of consecutive patients who underwent ESD for early EAC from August 2015 through February 2020. Primary outcomes included the clinical outcomes of noncurative ESDs along with overall en bloc, R0 and curative resection rates. Secondary outcomes included comparing results between T1a and T1b tumors.

Results

Final group included 23 T1a and 17 T1b EAC patients. Patients’ median Charlson comorbidity index was five. En bloc resection rate was (97.5%). Compared to the T1b group, the T1a group had a statistically significantly higher R0 (78.3 vs. 41.2%; P = 0.0235), curative (73.9 vs. 11.8%; P = 0.0001) and accumulative endoscopic curative resection rates (82.6 vs. 23.5%; P = 0.0003). A study flowchart is presented in (Fig. 1). Out of the 21 noncurative ESDs, 10 patients (47.6%) underwent R0 esophagectomy, 6 patients (28.6%) are undergoing surveillance endoscopies without additional therapy, 3 patients (14.3%) underwent repeat curative ESD and 1 patient (4.76%) is receiving chemotherapy with surveillance endoscopy. Over median endoscopic follow-up of 22.5 months (IQR, 14.25–30.75), 2 out of 10 patients with noncurative ESDs had recurrent disease.

Conclusions:

ESD achieved a higher curative resection rate in T1a EAC when compared to T1b. Despite a lower curative resection rate in T1b EAC, certain patients might benefit from a conservative multimodal therapy.
Advancing flexible endoscopy to natural orifice transluminal endoscopic surgery
Authors: Ullah Saif , Ali Faisal S. , Liu Bing-Rong
Published: June 2021

Purpose of review

This review is an update on the recent advancements and clinical applications of flexible endoscopy in the context of natural orifice translumenal endoscopic surgery (NOTES). We focus on recent developments in gastrointestinal luminal and transluminal NOTES.

Recent findings

NOTES has evolved from a hybrid approach utilizing a laparoscopic assistant to pure NOTES without laparoscopic assistance. Current experimental and clinical studies focus on the implementation of new minimally invasive approaches as well as on the training in the use of these procedures. In recent years, flexible endoscopic-NOTES and endoluminal surgery have increasingly reported favorable results in preclinical and experimental settings using flexible endoscopic cholecystectomy, cholecystolithotomy, and appendectomy. Additionally, flexible endoscopic lymphadenectomy and thyroidectomy are among the new interventions that are opening new frontiers for endoscopists to explore.

Flexible endoscopy has paved way to new frontiers for endoscopists and surgeons. As the armamentarium of interventional endoscopy increases and the ability of endoscopists to perform advanced interventions safely fosters an inevitable step forward that will involve the integration of new technology with innovative thinking.
Interventional endoscopic ultrasound
Authors: Dietrich Christoph F. , Braden Barbara , Jenssen Christian
Published: June 2021

Purpose of review

To update on recent advances in interventional endoscopic ultrasound (INVEUS) techniques.

Recent findings

The introduction of linear echoendoscopes with larger instrument channels and the combined development of new tools and devices have enabled various new applications of minimally invasive endoscopic ultrasound (EUS)-guided transluminal interventions of the pancreas, biliary system and peri-gastrointestinal structures. In this review, EUS-guided interventions are discussed and evaluated: drainage of peripancreatic fluid collections, access and drainage of bile ducts, gallbladder and pancreatic duct, treatment of gastrointestinal haemorrhage, coeliac plexus block and coeliac plexus neurolysis, fiducial placement, solid and cystic tumour ablation, drug delivery and brachytherapy, gastroenterostomy, angiotherapy and other EUS-guided applications. The EUS-guided interventions are classified based on the available evidence as established or experimental, standardized or nonstandardized procedures in common or rare diseases with well or little known complications and their established or nonestablished treatment.

Some EUS-guided interventions have sparse published evidence with only single-centre studies, case series or individual case reports, others like drainage of peripancreatic fluid collections have become widely accepted practice. INVEUS has been accepted as an alternative to several surgical approaches, EUS-guided techniques result in faster recovery times, shorter hospital stay and lower costs.
Iron Balance and Iron Nutritional Status in Preterm Infants During the First Four Months of Life
Authors: Cooke Richard J. , Griffin Ian
Published: June 2021

Objectives:

To determine whether iron absorption occurs in a dose-dependent fashion and/or is a function of iron nutritional status (INS) in preterm infants during the first 4 months of life.

Methods:

Preterm very-low-birth-weight infants (VLBWI) were fed an iron-fortified (0.7 mg/dL) infant formula. Three 48 h balance studies were performed on each infant. INS was determined by serially measuring hemoglobin, mean corpuscular volume (MCV), hematocrit, ferritin, transferrin and transferrin saturation levels. The data were analyzed using ANOVA and stepwise regression.

Results:

Fifty-four balance studies were performed in 18 infants (birth weight, 1347 ± 201 g; gestation, 30 ± 1.3 weeks; mean ± standard deviation) at 33 ± 1.3, 34 ± 1.2, and 48 ± 0.5 weeks corrected age and weights of 1768 ± 260, 2298 ± 314, 5127 ± 939 g. No relationship was detected between iron intake and absorption. Intake decreased during the study (1.17 ± .08, 1.24 ± 0.11 > 1.1 ± 0.15 mg · kg−1 · day−1) but net (0.32 ± 0.26, 0.36 ± 31 < 0.49 ± .23 mg · kg−1 · day−1) and % (27 ± 22, 29 ± 23 < 46 ± 21) absorption increased (P < 0.01). Serum ferritin, transferrin saturation and MCV fell, while hematocrit and hemoglobin remained stable. No relationship was noted between serum ferritin and iron absorption but transferrin saturation (54%), MCV (7%), and hematocrit (6%) accounted for 67% of the variation in iron absorption (P < 0.001).

Conclusions:

At intakes of 0.8–1.4  mg · kg−1 · day−1, iron absorption is not dose-dependent nor affected by iron stores. Only when iron delivery to the tissues decreases does absorption increase to meet needs in these otherwise normal and rapidly growing infants.
Neutrophil to Lymphocyte Ratio and Gastrointestinal Involvement Among Henoch Schonlein Purpura Patients: A Systematic Review and Meta-Analysis
Authors: Milas Gerasimos Panagiotis , Fragkos Stefanos
Published: June 2021

Neutrophil to lymphocyte ratio has been examined among several studies regarding Henoch Schonlein purpura patients with gastrointestinal involvement. The current meta-analysis aims to evaluate neutrophil to lymphocyte ratio differences between Henoch Schonlein purpura patients with and without gastrointestinal manifestations.

An extensive search of the available literature was done using MEDLINE (1966–2020), Clinicaltrials.gov (2008–2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2020) and Google Scholar (2004–2020) databases and statistical analysis was mainly conducted using RevMan 5.3 software.

The current meta-analysis is based on data from six studies. Neutrophil to lymphocyte ratio was higher in Henoch Schonlein patients with gastrointestinal involvement than those without with a mean difference of 0.88 (95% confidence interval [CI]: 0.55, 1.22 [P < 10–5, I
2 = 8%]). Low heterogeneity (I
2) was observed between the included studies. Subgroup analysis, leave one out meta-analysis and meta-regression analysis were performed which led to the lowering of I
2 to 0.

The findings of our meta-analysis suggest that the neutrophil to lymphocyte ratio could serve as a marker of gastrointestinal involvement in patients with Henoch Schonlein purpura; however, most of the included studies are case–control, therefore future cohort studies should clarify the value of this marker.
The Modified Bristol Stool Form Scale
Authors: Wegh Carrie A.M. , Hermes Gerben D.A. , Schoterman Margriet H.C. , Vaughan Elaine E. , Smidt Hauke , Belzer Clara , Benninga Marc A.
Published: June 2021

Objective:

The aim of the study was to assess whether the modified Bristol Stool Form Scale (m‐BSFS) is reliable, valid and user‐friendly to use by parents, grandparents, and day childcare employees to evaluate stool consistency in toilet and nontoilet‐trained toddlers in the Netherlands.

Study design:

Translation to Dutch and validity of the m‐BSFS (scoring 32 general stool pictures) for 1 to 3 year old toddlers (n = 89) was evaluated by parents, grandparents, and day childcare employees. A subgroup of participants scored an additional 7 pictures of stools in a diaper to validate the m‐BSFS for non‐toilet‐trained toddlers (n = 16). To determine inter‐rater reliability, 2‐way random effects single‐rater intraclass correlation coefficient (ICC)consistency was used. Intra‐rater reliability was measured by Cohen kappa (κ) by rating the same pictures in random order twice, with at least 1 week between the first and second scoring.

Results:

Inter‐ and intra‐rater reliability of the m‐BSFS were above recommended minimal standards of 0.61 for the 32 general stool pictures as well as for the 7 pictures of stools in a diaper. ICCconsistency for the general stool pictures of the first and second ratings were 0.71 (n = 89) and 0.79 (n = 77), respectively, with a κ of 0.71 (n = 77). ICCconsistency for the stools in diaper pictures of the first and second ratings were 0.93 (n = 16) and 0.93 (n = 15), respectively, with a κ of 0.77 (n = 15).

Conclusions:

The m‐BSFS is reliable, valid and user‐friendly to use by Dutch‐speaking parents, grandparents, and day childcare workers to evaluate stool consistency in both toilet‐ and nontoilet‐trained toddlers in the Netherlands.
Comparison of Symptom Control in Pediatric Gastroparesis Using Endoscopic Pyloric Botulinum Toxin Injection and Dilatation
Authors: Mercier Clémence , Ley Delphine , Aumar Madeleine , Lemale Julie , Fabre Alexandre , Colinet Stéphanie , Duhamel Alain , Gottrand Frédéric
Published: June 2021

Objectives:

The objective of this study was to assess the tolerance and efficacy of endoscopic intrapyloric botulinum toxin injection compared with pyloric dilatation in children with gastroparesis.

Methods:

This was a retrospective descriptive multicentre study that included pediatric patients treated between 2010 and 2018 at 4 tertiary hospitals.

Results:

Data were collected for 24 patients. The median age at diagnosis was 2.5 years (range 0.5–4.7). A total of 46 endoscopic procedures were performed. The endoscopic procedure was multiple in 63% of patients. Among the interventions, 76% were successful and 15% were unsuccessful. The recurrence rate was 57% and the median time to recurrence was 3.7 months (0.1–73). The efficacy did not differ significantly between the 2 methods at the first intervention and as a second-line treatment. The recurrence rate also did not differ significantly between the 2 methods. No complications were reported. The median follow-up was 19.8 months (1.7–61.7).

Conclusions:

In this retrospective multicentre study, endoscopic management of gastroparesis by balloon dilatation or botulinum toxin was safe in children and seemed to be partially efficient within the first months. Symptoms recurred frequently and required repetition of the interventions.
Epstein-Barr Virus Status and Subsequent Thiopurine Exposure Within a Paediatric Inflammatory Bowel Disease Population
Authors: Harris Rachel E. , Hegde Vikas , Curtis Lee , Garrick Vikki , Gervais Lisa , Armstrong Lawrence , Delahunty Caroline , Eccleston Andrew , Al-Hourani Ghassan , Flynn Diana M. , Merrick Victoria , Barclay Andrew R. , Tayler Rachel , Hansen Richard , Russell Richard K.
Published: June 2021

The use of thiopurine therapy in Epstein-Barr virus (EBV)-naïve inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period; finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis; that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (P = 0.22); and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation; no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management; further research into this is required.
Regional Gastrointestinal Motility in Healthy Children
Authors: Brinck Christian Emil , Mark Esben Bolvig , Ejerskov Cecilie , Johansen Klaus Birkelund , Sutter Nanna , Schlageter Vincent , Drewes Asbjørn Mohr , Krogh Klaus
Published: June 2021

Objective:

The aim of the study was to evaluate the safety and use of the 3D-Transit system (Motilis SA, Lausanne, Switzerland) and to describe regional gastrointestinal transit times, segmental colonic transit times, and colonic movement patterns in healthy children.

Methods:

Twenty-one healthy children (11 girls, median age 10.5 years, range 7–15 years) were included. For evaluation of gastrointestinal transit times and colonic movement patterns, we used the minimally invasive electromagnetic 3D-Transit system. A small electromagnetic capsule (21.5 mm × 8.3 mm) was ingested and tracked through the gastrointestinal tract by a body-worn detector. Regional gastrointestinal transit times were assessed as time between capsule passage of anatomical landmarks. Colonic movement patterns were described and classified based on capsule movement velocity, direction, and distance.

Results:

One child could not swallow the capsule and 20 children completed the study without any discomfort or side-effects. Median whole gut transit time was 33.6 (range 10.7–80.5) hours, median gastric emptying time was 1.9 (range 0.1–22.1) hours, median small intestinal transit time was 4.9 (range 1.1–15.1) hours, and median colonic transit time was 26.4 (range 6.8–74.5) hours. Median ascending colon/cecum transit time was 9.7 (range 0.3–48.1) hours, median transverse colon transit time was 5.6 (range 0.0–11.6) hours, median descending colon transit time was 2.6 (range 0.01–22.3) hours, and median sigmoid colon/rectum transit time was 7.5 (range 0.1–31.6) hours. Colonic movement patterns among children corresponded to those previously described in healthy adults.

Conclusions:

The 3D-Transit system is a well-tolerated and minimally invasive method for assessment of gastrointestinal motility in children.
Association of Delayed Treatment of Chlamydial Infection and Gonorrhea in Pregnancy and Preterm Birth
Authors: Burdette Emily R. , Young Marisa R. , Dude Carolynn M. , Wall Kristin M. , Haddad Lisa B.
Published: June 2021

Background

Treating chlamydia and gonorrhea in pregnancy has been shown to decrease the associated risk of preterm birth in some studies. Delayed treatment of these infections among nonpregnant patients carries known consequences. It is unclear whether delayed treatment in pregnancy similarly increases adverse outcomes.

Methods

We conducted a retrospective cohort study of women who delivered at a safety-net hospital from July 2016 to June 2018. Women with at least one visit who were tested for chlamydia and gonorrhea were included. Women diagnosed after 36 weeks (preterm analysis) or 31 weeks (early preterm analysis) were excluded. We used multivariable logistic regression to examine the association between no infection, timely treatment (<1 week), and delayed treatment (>1 week, not treated) with preterm (<37 weeks) and early preterm (<32 weeks) birth.

Results

Among 3154 deliveries, 389 (12%) were preterm. Among 3107 deliveries, 74 (2%) were early preterm. In adjusted models, women with timely (adjusted odds ratio [aOR]; 1.7, 95% confidence interval [CI], 1.0–2.7) and delayed (aOR, 1.7; 95% CI, 1.1–2.5) treatments had increased odds of preterm birth. Similarly, women with timely (aOR, 2.5; 95% CI, 1.0–6.2) and delayed (aOR, 2.4; 95% CI, 1.2–4.9) treatments had increased odds of early preterm birth. Among women who tested positive, multiple infections were not associated with an increase in preterm birth (preterm: 17% vs. 20%, P = 0.53; early preterm: 5% vs. 6%, P = 0.74).

Conclusions

Chlamydia and gonorrhea are associated with preterm and early preterm births, regardless of time to treatment. Creative solutions are needed to improve the prevention of these infections in pregnancy.
Case Series: Application of Topography-guided Contoura Refractive Surgery in Highly Irregular Cornea
Authors: Wang Xiangjun , Xu Wenwen , Xu Yanyun , Wang Chuanyu , Mu Guoying
Published: June 2021

SIGNIFICANCE

Highly irregular cornea leads to poor vision, glare, and starbursts. Although treatment is still at the exploration stage, topography-guided Contoura surgery has excellent potential for the treatment of highly irregular corneas.

PURPOSE

This case series reviews three patients (one with abnormal back elevation, one with corneal scar after fungal keratitis, and one with post–laser-assisted in situ keratomileusis central islands) treated with topography-guided Contoura surgery.

CASE REPORTS

In case 1, a 19-year-old man underwent topography-guided Contoura refractive surgery in the left eye and wavefront-optimized ablation in the right eye. Post-operative topography of the right eye showed marked inferior steepening and central irregular astigmatism compared with the contralateral eye. In case 2, a 53-year-old man presented with corneal scarring on the right eye after recovering from fungal keratitis. The patient first underwent phototherapeutic keratectomy and photorefractive keratectomy to remove the scarring primarily. He then underwent Contoura to correct hyperopia, which flattened the cornea and improved his vision significantly. In case 3, a 25-year-old man presented with central steepening on topography maps after undergoing laser-assisted in situ keratomileusis. He underwent topography-guided ablation, which improved his visual acuity and normalized the cornea.

CONCLUSIONS

Therapy for highly irregular corneas includes wavefront-guided surgery, conservative treatment, corneal transplantation, rigid gas-permeable lenses, and so on. In this case series, topography-guided Contoura refractive surgery provided an excellent option for reducing topographic abnormalities and improving vision.
Ischemic Heart Disease Related Sudden Cardiac Death in Autopsied Cases
Authors: Fnon Nora F. , Hassan Hanan H. , Ibrahim Mahrous A.
Published: June 2021

Diagnosis of the underlying cause of sudden unexpected death in a previously healthy individual remains one of the important challenges in forensic practice. Ischemic heart disease is the most common cause of sudden death. The current study aims to investigate the incidence and pathology of sudden ischemic cardiac death in Egypt. All cases of sudden cardiac death (SCD) examined by different forensic departments throughout Egypt during the period of January 2010 through December 2014 were included. Cases underwent complete autopsy examination including a thorough gross and microscopic examination of the heart and great blood vessels. Of 535 cases of SCD diagnosed during the period of the study, coronary atherosclerosis was the principle finding in 420 (78.5%) cases. The highest numbers of deaths were reported in fifth and sixth decades with male preference. Other causes of SCD included myocarditis, cardiomyopathies, valvular heart disease, and hypertensive heart disease (7.8%, 4.1%, 4.1%, and 2.8%, respectively). There was severe stenosis (>75%) of at least 1 coronary artery in 74% of cases. Type VI atherosclerosis was found in 40.7% of cases. The left anterior descending branch was the most affected artery by atherosclerosis. Acute coronary pathological events were demonstrated in 27.6% of cases. Recent myocardial infarction was evident in 55.5% of cases, whereas old infarcts were demonstrated in 44.5% of cases. Features of hypertensive heart disease were present in 18.3% of cases. In conclusion, ischemic heart disease is the leading cause of SCD in Egypt.
Kratom-Associated Fatalities in Northern Nevada—What Mitragynine Level Is Fatal?
Authors: Schmitt Jessicia , Bingham Kaileigh , Knight Laura D.
Published: June 2021

Mitragyna speciosa, commonly known as the kratom tree, has been utilized in Southeast Asia for centuries for its opioid-like effects. Kratom has been available in the United States for the past decade and has grown increasingly popular despite a lack of clinical research to determine its safety. With its widespread use, there have been an increasing number of fatalities. This study aims to establish a potential lethal range for mitragynine, the active compound in kratom, by investigating the toxicology reports of 35 deaths in Northern Nevada between 2015 and 2020. Mitragynine concentrations ranged from 8.7 to 1800 ng/mL (n = 27) in cases with drug toxicity as the cause of death; in 1 case, the sole intoxicant was mitragynine with a blood concentration of 950 ng/mL. In cases with nonmitragynine causes of death, the concentration was 110 to 980 ng/mL (n = 8). There was no statistically significant difference in blood concentrations between cases where mitragynine was not listed as a cause of death (mean, 315 ± 297.2 ng/mL) and cases in which mitragynine contributed to death (mean, 269.4 ± 382.5 ng/mL; P < 0.201). A literature review is also presented.
Mucoacinar Carcinoma
Authors: Bundele Manish , Weinreb Ilan , Xu Bin , Chiosea Simion , Faquin William , Dias-Santagata Dora , Leon Marino , Hyrcza Martin , Seethala Raja R.
Published: June 2021

Mucoepidermoid carcinoma (MEC) is generally characterized by an admixture of mucous, epidermoid and intermediate type cells. Numerous variants morphologies are described and defined by stromal and/or cytoplasmic tinctorial characteristics. We now report 11 cases of MEC with serous acinar differentiation, reflecting a distal intercalated duct/acinar phenotype, which we designate as mucoacinar carcinomas. Seven patients were female while 4 were male with a mean age of 55 years (range: 21 to 72 y). Ten cases were from the parotid while 1 was from the submandibular gland. Mean size of the tumors was 1.8 cm (range: 0.7 to 4.5 cm). Three cases were low grade, 7 were intermediate grade, and 1 was high grade. Low to intermediate grade cases demonstrated prominent clear to vacuolated cells with focal serous acinar differentiation. The high-grade case showed a distinctive scattering of acinar cells interspersed between epidermoid cells. Periodic acid Schiff after diastase (9/9), SOX-10 (9/9), and DOG-1 (9/10) highlighted the acinar component. Six of 7 cases showed a focal acinar predominant NR4A3 expression. MAML2 fluorescence in situ hybridization was positive in all cases, in both acinar and mucoepidermoid components. Two cases tested by next generation sequencing showed standard CRTC1-MAML2 fusions. MSANTD3 and NR4A3 fluorescence in situ hybridization on the other hand were negative. Evidence thus suggests that mucoacinar carcinoma represents an acinar variant morphology in MEC, rather than a true MEC-acinic cell carcinoma hybrid, or collision tumor. The acinar differentiation, SOX-10, DOG-1, and even focal NR4A3 reactivity may thus be diagnostic pitfalls.
Outcomes of Children With Firearm Injuries Admitted to the PICU in the United States*
Authors: Bagdure Dayanand , Foster Cortney B. , Garber Nan , Holloway Adrian , Day Jenni , Lee Jessica , Soto-Campos Gerardo , Brundage Nancy , Bhutta Adnan , Graciano Ana Lia
Published: June 2021

OBJECTIVES:

Firearm-related injury is the second leading cause of injury and death for children 1–18 years old in United States. The objective of our study was to analyze the outcomes of children admitted to the PICU with firearm injuries.

DESIGN:

Retrospective study.

SETTING:

PICUs in United States contributing data to Virtual Pediatric Systems, LLC, from January 2009 to December 2017.

PATIENTS:

Children age 1 month to 18 years old admitted to the PICU with firearm injury, identified by external cause of injury E-codes and International Classification of Diseases, 9th Edition, and International Classification of Diseases, 10th Edition, codes were identified.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

There were 1,447 cases identified of which 175 (12%) died in the PICU. Unintentional firearm injury (67.7%) and assault with a firearm injury (20%) comprised 90% of the cases. Males comprised 78% of the cohort (1,122) and race distribution included 45% Black (646), 27% White (390), and 12% Hispanic (178). Among the children who died in the PICU, 55% were 13–18 years old. Children attempting suicide with a firearm were more likely to die in the PICU as compared to the other causes of firearm injury. Based on their Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores at discharge, there is high morbidity in children with firearm injuries.

CONCLUSIONS:

Mortality rate of children with firearm injury admitted to the PICU is high. Children admitted to the PICU with suicide attempt with a firearm carried the highest mortality. Further studies may help further define the epidemiology of firearm injuries in children and plan interventions to minimize these unnecessary deaths.
Pilot and Feasibility Studies in Rehabilitation Research
Authors: Lawson Daeria O. , Mellor Katie , Eddy Saskia , Lee Christopher , Kim Kwang Hyun , Kim Kunmo , Mbuagbaw Lawrence , Thabane Lehana
Published: June 2021

Pilot and feasibility studies are conducted early in the clinical research pathway to evaluate whether a future, definitive study can or should be done and, if so, how. Poor planning and reporting of pilot and feasibility studies can compromise subsequent research efforts. Inappropriate labeling of studies as pilots also compromises education. In this review, first, a systematic survey of the current state of pilot and feasibility studies in rehabilitation research was performed, and second, recommendations were made for improvements to their design and reporting. In a random sample of 100 studies, half (49.5%) were randomized trials. Thirty (30.0%) and three (3.0%) studies used “pilot” and “feasibility” in the study title, respectively. Only one third (34.0%) of studies provided a primary objective related to feasibility. Most studies (92.0%) stated an intent for hypothesis testing. Although many studies (70.0%) mentioned outcomes related to feasibility in the methods, a third (30.0%) reported additional outcomes in the results and discussion only or commented on feasibility anecdotally. The reporting of progression plans to a main study (21.0%) and progression criteria (4.0%) was infrequent. Based on these findings, it is recommended that researchers correctly label studies as a pilot or feasibility design based on accepted definitions, explicitly state feasibility objectives, outcomes, and criteria for determining success of feasibility, justify the sample size, and appropriately interpret and report the implications of feasibility findings for the main future study.
The Intermittent Abdominal Pressure Ventilator as an Alternative Modality of Noninvasive Ventilatory Support
Authors: Pierucci Paola , Di Lecce Valentina , Carpagnano Giovanna Elisiana , Banfi Paolo , Bach John R.
Published: June 2021

Noninvasive ventilation has become the initial treatment for symptomatic ventilatory pump failure but, when used at ventilatory support settings, can be an alternative to tracheostomy mechanical ventilation. The intermittent abdominal pressure ventilator, a corset with an internal air sack inflated by a ventilator, allows to increase tidal volumes through the raising of the diaphragm and its consequent passive descent. It has been used for daytime support for more than 70 yrs, but its knowledge among clinicians is scarce. A narrative review was performed by searching PubMed, Medline, and the Cochrane Database of Systematic Reviews using the terms “IAPV” or “pneumobelt.” One hundred forty patients were cited using the intermittent abdominal pressure ventilator from 1946 until it went off the market in the 1970s, although many continued to use it. There was only one publication on its use from 2003 to 2017, but three publications from 2017 through 2021. It has been used for full diurnal ventilatory support by some patients for more than 50 yrs and has even been used throughout the labor of a mother with no ventilator-free breathing ability. The intermittent abdominal pressure ventilator is a ventilatory support alternative for patients with ventilatory pump failure. It can be effective and well tolerated and maintain quality of life without facial interfaces. More widespread application is warranted.
Perceived Benefits of a Cadaver-Based Ultrasound Procedure Workshop for Physical Medicine and Rehabilitation Trainees
Authors: Bushi Sharon , Kirshblum Steven , Ezepue Tiffany , Ma Rex
Published: June 2021

Ultrasound-guided musculoskeletal and spasticity injections have become common procedures in physical medicine and rehabilitation practices, but there are currently no guidelines for teaching these procedures in residency and fellowship training programs. As part of a quality improvement initiative, the authors aimed to assess the educational value of a hands-on cadaver-based workshop for enhancing these skills in residents and fellows. Twenty-seven physical medicine and rehabilitation trainees in a single institution were asked to complete surveys before and after the workshop to assess self-perceived benefits. After the workshop, the overwhelming majority felt improvement in their overall knowledge of ultrasound-guided musculoskeletal (93%) and spasticity (78%) procedures. In addition, the workshop improved the level of comfort of trainees both in planning (70%) and performing (59%) the procedures independently. Improving these skills is especially important considering most trainees plan to incorporate ultrasound-guided musculoskeletal (81%) and spasticity (74%) procedures into their future practices. The framework for this workshop can serve as a template for other programs to incorporate into their own training.
Disrupted Access to Therapies and Impact on Well-Being During the COVID-19 Pandemic for Children With Motor Impairment and Their Caregivers
Authors: Sutter Ellen N. , Francis Linda Smith , Francis Sunday M. , Lench Daniel H. , Nemanich Samuel T. , Krach Linda E. , Sukal-Moulton Theresa , Gillick Bernadette T.
Published: June 2021

Objectives

The aim of this study was to determine the impact of the COVID-19 pandemic on access to rehabilitation therapies and the impact of changes in therapy access on the physical and mental well-being of children with motor impairment and their caregivers.

Design

Caregivers of children younger than 18 yrs with childhood-onset motor impairment (primarily cerebral palsy) completed an anonymous survey through the online platform REDCap between May 5 and July 13, 2020.

Results

The survey was completed by 102 participants. Before the pandemic, 92 of 102 children (90%) were receiving one or more therapies; at the time surveyed, 55 children (54%) were receiving any therapies (P < 0.001). More than 40% of the sample reported increased child stress, decreased physical activity, and/or decline in mobility/movement. Participants who reported a decrease in number of therapies at the time surveyed more frequently reported lower satisfaction with treatment delivery (P < 0.001), a decline in child’s mobility (P = 0.001), and increased caregiver stress (P = 0.004). Five qualitative themes were identified from open-ended question responses related to therapies and well-being.

Conclusions

Access to pediatric rehabilitation therapies was disrupted during COVID-19. Disrupted access may be related to impact on physical and mental health. With the expansion of telehealth, caregiver and child feedback should be incorporated to optimize benefit.
Short-term Outcomes After Spleen-preserving Minimally Invasive Distal Pancreatectomy With or Without Preservation of Splenic Vessels
Authors: Korrel Maarten , Lof Sanne , Al Sarireh Bilal , Björnsson Bergthor , Boggi Ugo , Butturini Giovanni , Casadei Riccardo , De Pastena Matteo , Esposito Alessandro , Fabre Jean Michel , Ferrari Giovanni , Fteriche Fadhel Samir , Fusai Giuseppe , Koerkamp Bas Groot , Hackert Thilo , D’Hondt Mathieu , Jah Asif , Keck Tobias , Marino Marco V. , Molenaar I. Quintus , Pessaux Patrick , Pietrabissa Andrea , Rosso Edoardo , Sahakyan Mushegh , Soonawalla Zahir , Souche Francois Regis , White Steve , Zerbi Alessandro , Dokmak Safi , Edwin Bjorn , Hilal Mohammad Abu , Besselink Marc ,   for the European consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)
Published: June 2021

Objective:

To compare short-term clinical outcomes after Kimura and Warshaw MIDP.

Background:

Spleen preservation during distal pancreatectomy can be achieved by either preservation (Kimura) or resection (Warshaw) of the splenic vessels. Multicenter studies reporting outcomes of Kimura and Warshaw spleen-preserving MIDP are scarce.

Methods:

Multicenter retrospective study including consecutive MIDP procedures intended to be spleen-preserving from 29 high-volume centers (≥15 distal pancreatectomies annually) in 8 European countries. Primary outcomes were secondary splenectomy for ischemia and major (Clavien-Dindo grade ≥III) complications. Sensitivity analysis assessed the impact of excluding (“rescue”) Warshaw procedures which were performed in centers that typically (>75%) performed Kimura MIDP.

Results:

Overall, 1095 patients after MIDP were included with successful splenic preservation in 878 patients (80%), including 634 Kimura and 244 Warshaw procedures. Rates of clinically relevant splenic ischemia (0.6% vs 1.6%, P = 0.127) and major complications (11.5% vs 14.4%, P = 0.308) did not differ significantly between Kimura and Warshaw MIDP, respectively. Mortality rates were higher after Warshaw MIDP (0.0% vs 1.2%, P = 0.023), and decreased in the sensitivity analysis (0.0% vs 0.6%, P = 0.052). Kimura MIDP was associated with longer operative time (202 vs 184 minutes, P = 0.033) and less blood loss (100 vs 150 mL, P < 0.001) as compared to Warshaw MIDP. Unplanned splenectomy was associated with a higher conversion rate (20.7% vs 5.0%, P < 0.001).

Conclusions:

Kimura and Warshaw spleen-preserving MIDP provide equivalent short-term outcomes with low rates of secondary splenectomy and postoperative morbidity. Further analyses of long-term outcomes are needed.
The Association of Postoperative Opioid Prescriptions with Patient Outcomes
Authors: Howard Ryan , Brown Craig S. , Lai Yen-Ling , Gunaseelan Vidhya , Chua Kao-Ping , Brummett Chad , Englesbe Michael , Waljee Jennifer , Bicket Mark C.
Published: June 2021

Objective:

To compare outcomes after surgery between patients who were not prescribed opioids and patients who were prescribed opioids.

Summary of Background Data:

Postoperative opioid prescriptions carry significant risks. Understanding outcomes among patients who receive no opioids after surgery may inform efforts to reduce these risks.

Methods:

We performed a retrospective study of adult patients who underwent surgery between January 1, 2019 and October 31, 2019. The primary outcome was the composite incidence of an emergency department visit, readmission, or reoperation within 30 days of surgery. Secondary outcomes were postoperative pain, satisfaction, quality of life, and regret collected via postoperative survey. A multilevel, mixed-effects logistic regression was performed to evaluate differences between groups.

Results:

In a cohort of 22,345 patients, mean age (standard deviation) was 52.1 (16.5) years and 13,269 (59.4%) patients were female. About 3175 (14.2%) patients were not prescribed opioids, of whom 422 (13.3%) met the composite adverse event endpoint compared to 2255 (11.8%) of patients not prescribed opioids (P = 0.015). Patients not prescribed opioids had a similar probability of adverse events {11.7% [95% confidence interval (CI) 10.2%−13.2%] vs 11.9% (95% CI 10.6%–13.3%]}. Among 12,872 survey respondents, patients who were not prescribed an opioid had a similar rate of high satisfaction [81.7% (95% CI 77.3%–86.1%) vs 81.7% (95% CI 77.7%– 85.7%)] and no regret [(93.0% (95% CI 90.8%–95.2%) vs 92.6% (95% CI 90.4%–94.7%)].

Conclusions:

Patients who were not prescribed opioids after surgery had similar clinical and patient-reported outcomes as patients who were prescribed opioids. This suggests that minimizing opioids as part of routine postoperative care is unlikely to adversely affect patients.
The Impact of Adjuvant Hemithoracic Radiation on Outcomes in Patients With Stage I-III Malignant Pleural Mesothelioma
Authors: Raman Vignesh , Voigt Soraya L. , Jawitz Oliver K. , Farrow Norma E. , Rhodin Kristen E. , Yang Chi-Fu Jeffrey , Tong Betty C. , D’Amico Thomas A. , Harpole David H.
Published: June 2021

Background:

The outcomes associated with receipt of adjuvant radiation in patients after surgery for MPM are poorly understood.

Objective:

The objective of this study was to use 2 registries to compare the outcomes of patients receiving adjuvant radiation or no radiation after definitive surgery for pathologic stage I–III MPM.

Methods:

Patients with resected pathologic stage I–III MPM were identified from the Duke University registry (1996–2016) and National Cancer Database (NCDB) (2004–2015). The primary outcome was overall survival. Propensity score-matched and landmark subgroup analyses were performed.

Results:

A total of 212 institutional and 1615 NCDB patients met criteria. In both cohorts, patients who underwent radiation were more likely to have margin-negative resection and more advanced pathologic stage. At a landmark time of 4.4 and 4.7 months from surgery, Duke [hazard ratio (HR) 1.14; 95% confidence interval (CI) 0.62–2.11] and NCDB patients (HR 0.97; 95% CI 0.81–1.17) who received adjuvant radiation did not experience improved survival compared to those who did not receive radiation in multivariable analysis. Duke patients who received radiation had similar incidence of recurrence and time to both overall recurrence and ipsilateral recurrence (HR 0.87; 95% CI 0.43–1.77) compared to those who did not. Duke patients experienced 100 grade 1/2, 21 grade 3/4, and one grade 5 toxicity events during radiation.

Conclusions:

In this dual registry analysis of patients with resected stage I–III MPM, the receipt of adjuvant hemithoracic radiation was not associated with improved survival compared to no radiation.
Small Bowel Obstruction After Laparoscopic Roux-en-Y Gastric Bypass Caused by Hemobezoar: A Case Series and Review of Literature
Authors: Caputo Viviana , Facchiano Enrico , Soricelli Emanuele , Leuratti Luca , Quartararo Giovanni , Lucchese Marcello
Published: June 2021

Background:

The development of an intraluminal blood clot (hemobezoar), represents a rare cause (0.05% to 1.9%) of small bowel obstruction (SBO) after laparoscopic Roux-en-Y gastric bypass (LRYGB). We present a case series of 6 cases of SBO caused by hemobezoar.

Methods:

A retrospective analysis of a prospective database including patients who underwent LRYGB from January 2010 to December 2019 has been performed. All the patients who underwent reoperation because of an SBO caused by an intraluminal blood clot were included in the present study.

Results:

Six of 843 LRYGB patients developed an hemobezoar (0.71%). Primary LRYGB was uneventful in all cases. SBO symptoms developed after a mean interval of 26.6 hours from the primary procedure. All reoperations were performed with the laparoscopic approach. In all cases, the hemobezoar was located at the level of the jejunojejunal anastomosis (JJA) and was removed through an enterotomy performed at the distal end of the biliopancreatic stump. Three postoperative complications occurred: 1 ab-ingestis pneumonia, 1 leak of the JJA requiring further reoperation, and 1 pelvic abscess treated with radiologic drainage. The mean hospital stay was 11 days.

Discussion:

SBO due to hemobezoar is a rare but worrisome early complication after LRYGB. It almost always affects the JJA and requires a prompt diagnosis to avoid dreadful sequelae. In the absence of anastomotic leak or stenosis, surgical management may consist of the removal of the blood clot without refashioning the anastomosis and it may be accomplished with the laparoscopic approach.
Antibody responses to BNT162b2 mRNA COVID-19 vaccine in 2,015 healthcare workers in a single tertiary referral hospital in Japan
Authors: Kageyama Takahiro , Ikeda Kei , Tanaka Shigeru , Taniguchi Toshibumi , Igari Hidetoshi , Onouchi Yoshihiro , Kaneda Atsushi , Matsushita Kazuyuki , Hanaoka Hideki , Nakada Taka-Aki , Ohtori Seiji , Yoshino Ichiro , Matsubara Hisahiro , Nakayama Toshinori , Yokote Koutaro , Nakajima Hiroshi
Published: June 2021

We measured antibody responses in 2,015 healthcare workers who were receiving 2 doses of BNT162b2 mRNA vaccine against SARS-CoV-2. The vast majority (99.9%) had either seroconversion or a substantial increase in antibody titer. A multivariate linear regression model identified predictive factors for antibody responses which may have clinical implications.