bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular cytogenetic characterization of a mosaic small supernumerary marker chromosome derived from chromosome Y in an azoospermic male
Authors: Zhang Hongguo , Liu Xiangyin , Geng Dongfeng , Yue Fagui , Jiang Yuting , Liu Ruizhi , Wang Ruixue
Published: July 2019

Rationale:

Small supernumerary marker chromosomes (sSMCs) can be usually discovered in the patients with mental retardation, infertile couples, and prenatal fetus. We aim to characterize the sSMC and explore the correlation between with sSMC and male infertility.

Patient concerns:

A 26-year-old Chinese male was referred for infertility consultation in our center after 1 year of regular unprotected coitus and no pregnancy.

Diagnosis:

Cytogenetic G-banding analysis initially described a mosaic karyotype 47,X,Yqh-,+mar[28]/46,X,Yqh-[22] for the proband, while his father showed a normal karyotype. The chromosome microarray (CMA) analysis showed there existed a duplication of Yp11.32q11.221, a deletion of Yq11.222q12, a duplication of 20p11.1 for the patient. Azoospermia factor (AZF) microdeletion analysis for the patient showed that he presented a de novo AZFb+c deletion. Fluorescence in situ hybridization further confirmed the sSMC was an sSMC(Y) with SRY signal, Y centromere, and Yq deletion.

Interventions:

The patient would choose artificial reproductive technology to get his offspring according to the genetic counseling.

Outcomes:

The sSMC in our patient was proved to be an sSMC(Y), derived from Yq deletion. The spermatogenesis failure of the proband might be due to the synthetic action of sSMC(Y) mosaicism and AZFb+c microdeletion.

Lessons:

It is nearly impossible to detect the chromosomal origin of sSMC through traditional banding techniques. The molecular cytogenetic characterization could be performed for identification of sSMC so that comprehensive genetic counseling would be offered.
Polyneuropathy in Critically Ill Mechanically Ventilated Children: Experience From a Tertiary Care Hospital in North India*
Authors: Shubham Shantanu , Dhochak Nitin , Singh Akanksha , Patel Sanjay Kumar , Chakrabarty Biswaroop , Sankar Jhuma , Gulati Sheffali , Kabra S. K. , Jaryal Ashok Kumar , Lodha Rakesh
Published: July 2019

Objectives:

To determine the prevalence of critical illness polyneuropathy and its risk factors in critically ill children mechanically ventilated for 7 days or more.

Design:

Observational cohort study.

Setting:

PICU of a tertiary care hospital from North India.

Patients:

Children 1–15 years old admitted in PICU from June 2016 to September 2017, mechanically ventilated for 7 days or more, excluding those with diagnosed neuromuscular disease, stroke, or spinal pathology.

Intervention:

Demographic details, diagnosis, treatment details, and anthropometry at admission and enrolment were recorded. Nerve conduction studies were performed after enrolment and repeated a week later, if the child was still in PICU. Medical Research Council scoring for muscle strength was performed in survivors. Risk factors including Pediatric Index of Mortality-2 score, sepsis, multiple organ dysfunction, hypoalbuminemia, use of steroids, neuromuscular-blocking agents, and vasopressors were recorded. Samples for the level of micronutrients (copper, zinc, folate, and vitamin B12) were collected at the time of enrolling the child and at the time of discharge.

Measurements and Main Results:

Thirty-two children were enrolled, of whom 29 had features of critical illness polyneuropathy on evaluation at day 8 of mechanical ventilation (prevalence, 90.6% [95% CI, 80.5–100%]). The polyneuropathy was axonal in 26 (81.2%), mixed in one patient (3.1%), and uncharacterized in two (6.2%). Sepsis and multiple organ dysfunction were present in 31 subjects (96.9%). No risk factors for critical illness polyneuropathy could be identified although the study was not sufficiently powered to do so. The difference between serum micronutrient levels (copper, zinc, folate, and vitamin B12) between patients who developed polyneuropathy, and those who did not, was statistically insignificant.

Conclusions:

We observed a high prevalence of critical illness polyneuropathy in children in PICU, mechanically ventilated for 7 days or more; almost all of whom had underlying sepsis.
A Comparative Analysis of Telephone and In-Person Survey Administration for Public Health Surveillance in Rural American Indian Communities
Authors: English Kevin C. , Espinoza Judith , Pete Dornell , Tjemsland Amanda
Published: July 2019

Objective:

Public health surveillance systems suffer from insufficient inclusion of American Indian/Alaska Native (AI/AN) populations. These health surveys have also gravitated to telephone administration because of the rising cost of face-to-face interviewing. Several studies have demonstrated that telephone surveys underrepresent people with low incomes, less educational attainment, and minorities. This study assessed the impact of administration mode upon survey participation in rural AI/AN tribes.

Design:

Using a modified Behavioral Risk Factor Surveillance System instrument, the Albuquerque Area Southwest Tribal Epidemiology Center partnered with 3 tribes to administer the survey to a target population of 900 AI/AN adults. Half of the sample was assigned to telephone survey administration and the other half was surveyed in-person by trained community interviewers. Significance testing was performed to assess differences in response rates, demographic characteristics, and costs by survey administration type.

Results:

Several notable differences between the survey administration modes were observed. In-person administration yielded a higher response rate (68.8%) than the telephone survey (35.7%). Likewise, in-person participants were, on average, younger and had lower household incomes and educational attainment than those who completed the survey via telephone. In-person survey administration was also slightly more cost-effective than telephone administration ($192 vs $211 per completed survey) due to the low response rate of telephone administration.

Conclusions:

The findings from this study have important implications for public health surveillance with rural AI/AN populations, where telephone survey administration is unlikely to yield sufficient coverage of this underserved population. This discovery is particularly disconcerting, given the fact that face-to-face interviewing has largely been replaced by telephone interviewing (and increasingly mobile phones) for public health surveillance in the United States. Without change and innovation, the AI/AN population will continue to lack meaningful health data, further challenging capacity to document and address persistent disparities and inequities witnessed among AI/ANs nationwide.
Survey Development: Community Involvement in the Design and Implementation Process
Authors: Kelley Allyson , Piccione Christopher , Fisher Aryn , Matt Karly , Andreini Michael , Bingham Dyani
Published: July 2019

Documenting Tribal health priorities is needed to inform research agendas, policy efforts, advocacy, and funding. However, published literature rarely documents the methods used to develop surveys in Indigenous communities. This methods paper includes two objectives: (1) increase knowledge and understanding about the importance of community involvement in public health activities; and (2) provide an example of how the Rocky Mountain Tribal Leaders Council Epidemiology Center (RMTEC) worked with one Tribal community to develop a health priorities survey. This paper describes how the RMTEC worked with a Tribal community and Tribal College students to develop, pilot, and revise a health priorities survey. Recommendations focus on the need for more culturally-responsive survey methods, the importance of building Tribal capacity for health research, and the value of piloting surveys in communities prior to implementation.
An Evaluation of Hepatitis C Virus Telehealth Services Serving Tribal Communities: Patterns of Usage, Evolving Needs, and Barriers
Authors: Stephens David , Leston Jessica , Terrault Norah A. , Gailloux Keri , Mera Jorge , Essex Whitney , Reilley Brigg
Published: July 2019

Introduction:

American Indian/Alaska Native (AI/AN) populations are disproportionately affected by chronic hepatitis C virus (HCV) infection. Federal facilities of the Indian Health Service, in conjunction with Tribally operated and Urban Indian (I/T/U) health care facilities, serve an estimated 2.2 million AI/AN patients. The facilities are mainly rural and have few specialists. To fill the gap in specialists in I/T/U clinics, the Extension for Community Healthcare Outcomes (ECHO) telehealth model was used to support clinicians to treat HCV in primary care.

Methods:

Participants in 3 regional HCV ECHO networks serving AI/AN patients were surveyed by e-mail and text message to determine patterns of ECHO usage, usefulness, and barriers to treating patients with HCV at their primary care clinics.

Results:

From a total of 44 respondents from 72 eligible health care facilities, a majority (61%) stated that they started treating patients with HCV subsequent to participating in the telehealth program. Participants with more telehealth experience sought increasing complexity in patient case presentations. In California, 7 of 8 clinicians who had attended more than 10 ECHO sessions expressed diminishing need for ECHO sessions to manage cases (<25% of patients). All elements of the ECHO sessions (presenting patient cases, listening to patient case presentations, teaching sessions, and sharing of programmatic insights) were considered “extremely useful” by the majority of respondents. The factors most cited as moderate or extensive barriers to providing HCV care were access to HCV direct acting antivirals (60%) and linking patients to care (50%).

Discussion:

Extension for Community Healthcare Outcomes may play a key role not only in increasing clinical capacity for HCV treatment but also in the inception of HCV services in this sample of I/T/U facilities. Participants with more telehealth experience demonstrated signs of increasing clinical capacity, where they were more likely to seek complex patient case presentations in ECHO sessions. A number of barriers continue to keep AI/ANs from being cured and stop clinicians from ending the epidemic, including access to HCV medications, time to provide HCV clinical services, and linking patients to HCV services.
Supersonic Transporter Deformity in Transgender Men following Phalloplasty
Authors: Salgado Christopher J. , Fein Lydia A. , Williams Eva A. , Sood Rachita
Published: July 2019

Phalloplasty is often the final stage of gender-affirmation surgery for transgender men. Obtaining penile rigidity is important for sexual function, but may also bring complications, including supersonic transporter deformity, in which the glans becomes ventrally displaced and flaccid. Two cases of supersonic transporter deformity are presented here, one with a hydraulic penile implant and one with an autologous bone transplant. Attempt at surgical correction was performed in both. Careful attention must be paid to the unique anatomy of the neophallus and type of penile prosthesis to prevent or correct supersonic transporter deformity in transgender men.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Virtual Reality Improves the Patient Experience during Wide-Awake Local Anesthesia No Tourniquet Hand Surgery: A Single-Blind, Randomized, Prospective Study
Authors: Hoxhallari Ediana , Behr Ian J. , Bradshaw Jonathan S. , Morkos Michael S. , Haan Pam S. , Schaefer Maureen C. , Clarkson James H. W.
Published: July 2019

Wide-awake local anesthesia no tourniquet surgery has been shown to decrease cost and hospital length of stay. The authors studied the use of virtual reality during wide-awake local anesthesia no tourniquet outpatient upper extremity surgery to assess its effect on patient pain, anxiety and fun. Patients undergoing wide-awake local anesthesia no tourniquet surgery were randomized to use (virtual reality) or not use (non–virtual reality) virtual reality during their procedures. Pain, fun, and anxiety were measured with a Likert scale at several time points, as were blood pressure and heart rate. A postoperative questionnaire was used to assess overall satisfaction. Virtual reality patients exhibited lower anxiety scores during injection, during the procedure, and at the end of the procedure. There were no differences in blood pressure, heart rate, or pain scores. Compared with non–virtual reality patients, virtual reality patients’ fun scores were higher. Virtual reality patients felt the experience helped them to relax, and they would recommend virtual reality–assisted wide-awake local anesthesia no tourniquet surgery. Among patients with self-reported preexisting anxiety, virtual reality patients had lower pain and anxiety scores during injection of local anesthesia compared with non–virtual reality patients. This study demonstrates that readily available virtual reality hardware and software can provide a virtual reality experience that reduces patient anxiety both during the injection of local anesthesia and during the surgical procedure. (Plast. Reconstr. Surg. 144: 408, 2019.)

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Customized Three-Dimensional Printing Spacers for Bone Positioning in Orthognathic Surgery for Correction and Prevention of Facial Asymmetry
Authors: Dumrongwongsiri Sarayuth , Lin Hsiu-Hsia , Niu Lien-Shin , Lo Lun-Jou
Published: July 2019

Orthognathic surgery is a powerful tool for correction of facial asymmetry and malocclusion. The goal is to achieve good dental function and facial aesthetics. Three-dimensional simulation is used for surgical planning, and bone gaps could be created to achieve facial balance. In this study, customized “spacers” were made using computer-aided design and three-dimensional printing for guides for use during surgery. With the final three-dimensional plan, the skull images were exported to 3-Matic software, where spacers were designed according to the bone gaps. Three-dimensionally–printed spacers were made and used to facilitate positioning and fixation. Consecutive patients with facial asymmetry were recruited in this prospective study. The postoperative outcome was assessed using a visual analogue scale and the three-dimensional facial surface area discrepancy index for subjective and objective evaluation. There were 12 patients and a total of 19 spacers for the Le Fort I and mandibular ramus segments. The spacers worked nicely during the bone fixation process. Mean preoperative and postoperative visual analogue scale scores were 4.83 and 7.14, with a statistically significant improvement for facial symmetry (p = 0.018). Mean preoperative and postoperative facial surface area discrepancy index was 0.95 and 0.98, and the correction of asymmetry was significant (p = 0.009). There were no related surgical complications. All patients were satisfied with the correction of facial asymmetry and malocclusion. The custom-made, three-dimensionally–printed spacers help to achieve surgical precision to correct and prevent facial asymmetry in orthognathic surgery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Appreciation of Postpartum Changes of the Rectus Muscles in Primary and Repeated Abdominoplasty
Authors: Janes Lindsay E. , Fracol Megan E. , Dumanian Gregory A.
Published: July 2019

Background:

Abdominoplasty is one of the top five most commonly performed cosmetic procedures. Whereas widening of the linea alba is a well-accepted consequence of pregnancy, the changes to the rectus abdominis muscles are less well known and thus unappreciated and undertreated.

Methods:

After institutional review board approval, the Northwestern Enterprise Data Warehouse identified nulliparous and multiparous women, aged 18 to 45 years, who underwent abdominal computed tomography between 2000 and the present. Measurements included the width and cross-sectional area of each rectus muscle, width of the linea alba, and circumference of the abdominal cavity at the level of the L3 vertebra. In addition, two case reports addressing these anatomical changes with muscle modification and mesh reinforcement are presented.

Results:

Sixty women were identified that met our inclusion criteria: 15 nulliparous, 15 after one pregnancy (para 1), 15 after two pregnancies (para 2), and 15 after three or more pregnancies (para ≥ 3). The linea alba was significantly widened after one pregnancy from 1.14 cm to 2.29 cm, but did not significantly widen further with each subsequent pregnancy. The width of each rectus muscle was significantly widened from 6.00 ± 0.60 cm in nulliparous to 6.61 ± 0.58 cm in para 1, significantly widened again to 7.03 ± 0.46 cm in para 2, but not significantly widened after that (6.97 ± 1.00 cm in para 3).

Conclusions:

In addition to widening of the linea alba, pregnancy alters the shape of the rectus abdominis muscle. Correction of muscle width during abdominoplasty may be a necessary adjunct to achieve the proper tension in both primary and revision procedures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Innovations in the Plastic Surgery Care Pathway: Using Telemedicine for Clinical Efficiency and Patient Satisfaction
Authors: Funderburk Christopher D. , Batulis Nicole S. , Zelones Justin T. , Fisher Alec H. , Prock Kimberly L. , Markov Nickolay P. , Evans Alison E. , Nigriny John F.
Published: July 2019

Background:

Telemedicine delivers clinical information and permits discussion between providers and patients at a distance. Postoperative visits may be a burden to patients—many of whom travel long distances and miss work opportunities. By implementing a telehealth opportunity, the authors sought to develop a process that optimizes efficiency and provides optimal patient satisfaction.

Methods:

Using quality improvement methods that have been highly effective in the business sector, we developed a testable workflow for patients in the postoperative telehealth setting. Seventy-two patients were enrolled and surveyed. A preoperative survey sought to determine travel distance, comfort with technology, access to the Internet and video-enabled devices, and the patient’s interest in telehealth. A postoperative survey focused on patient satisfaction with the experience.

Results:

Using the Lean Six Sigma methodology, the authors developed a telehealth workflow to optimize clinical efficiency. Preoperative surveys revealed that the majority (73 percent) of patients preferred in-person follow-up visits in the clinic. However, the postoperative survey distributed after the telehealth encounter found that nearly 100 percent of patients were satisfied with the telehealth experience. Ninety-six percent of patients said that their questions were answered, and 97 percent of patients stated that they would use telehealth again in the future.

Conclusions:

Telehealth encounters enable real-time clinical decision-making by providing patients and visiting nurses access to providers and decreasing patient transportation needs and wait times. Although initially hesitant to opt for a telehealth encounter in lieu of a traditional visit, the great majority of patients voiced satisfaction with the telehealth experience.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Emerging concepts in the diagnosis, treatment, and prevention of travelers’ diarrhea
Authors: Schweitzer Lorne , Singh Bhagteshwar , Rupali Priscilla , Libman Michael
Published: July 2019

Purpose of review

Traveller's diarrhea, though not life-threatening. is often a vexing problem, which impacts overall function of the traveller while on holiday. Increasing data is available regarding molecular diagnostic techniques, which may help obtain an early etiologic diagnosis. Use of antibiotics for traveller's diarrhea is controversial in this era of multidrug resistance and microbiome disruption.

Recent findings

Travel to the tropics promotes gut colonization with drug-resistant bacteria and this risk increases after treatment with antibiotics, leading to potential ecological impacts in the country of residence.

Traveller's diarrhea is common and can impact a traveller's itinerary leading to significant inconvenience, and occasional longer term sequelae. Though bacterial causes predominate, recommended treatment is conservative in mild-to-moderate cases. Molecular techniques for early diagnosis of traveller's diarrhea may help with appropriate management. Treatment with antibiotics is sometimes required but is associated with gut colonization by multidrug-resistant bacteria.
Evidence of Prostate-Specific Membrane Antigen Expression in Hepatocellular Carcinoma Using 68Ga-PSMA PET/CT
Authors: Kuyumcu Serkan , Has-Simsek Duygu , Iliaz Raim , Sanli Yasemin , Buyukkaya Fikret , Akyuz Filiz , Turkmen Cuneyt
Published: July 2019

Introduction

Prostate specific membrane antigen (PSMA) expression has been demonstrated in tumor neovasculature of many solid tumors, including hepatocellular carcinoma (HCC). The purpose of this study is to evaluate PSMA expression in patients with HCC.

Materials and Methods

Nineteen HCC patients who underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) as part of restaging procedure also underwent 68Ga-PSMA PET. 18F-FDG PET and 68Ga-PSMA findings were compared visually as well as quantitatively using maximized standardized uptake values (SUVmax).

Results

FDG was positive in 15 patients while 16 patients demonstrated PSMA expression. The only extrahepatic finding was one metastatic lymph node detected by both tracers. Mean SUVmax of liver lesions on FDG PET/CT was 8.3 ± 2.3 and mean tumor to background ratio was 2.3 ± 1.5. Respective values for 68Ga-PSMA PET/CT were 17.4 ± 9 and 3.3 ± 2.2. On visual and quantitative evaluation uptake was higher with PSMA in nine patients and higher with FDG in four patients. PSMA and FDG activity were similar in three patients. One of the FDG positive patients was PSMA negative whereas two patients were PSMA positive but FDG negative. Heterogeneous uptake pattern was observed in three patients. Comparison of mean SUVmax and T/B values between PET studies revealed no statistically significant difference (P > 0.1). The mean survival was 25 months (range: 18–32 months) and SUVmax of PSMA (P = 0.05) and FDG (P = 0.012) showed medium strength of correlation with overall survival.

Conclusion

PSMA expression in advanced HCC can be demonstrated by 68Ga-PSMA PET but is not superior to FDG PET however it could be useful for identifying patients with limited therapeutic options.
Rapidly Progressing Renal Cell Cancer of the Left Native Kidney in a Renal Transplant Recipient With Unusual Sites of Metastasis Demonstrated in Serial 18F-FDG PET/CT
Authors: Rangan B K Kasturi , Ora Manish , Suraj Ajay Singh , Parashar Ashutosh , Gambhir Sanjay
Published: July 2019

An end-stage renal disease patient underwent renal transplantation 18 years back and was on triple immunosuppression for acute rejection. She presented with left-sided abdominal lump and underwent ultrasound and noncontrast CT scan, which revealed an exophytic mass lesion in atrophic left kidney (16.2 × 13.1 × 14 cm). Baseline 18F-FDG PET/CT revealed a large avid exophytic mass (SUVmax 23, 17 × 14 × 13) in atrophic left kidney, with multiple retroperitoneal lymphadenopathies and a suspicious lung nodule. She underwent left open radical nephrectomy. Follow-up PET/CT after 1 month revealed multiple soft tissue deposits in operative bed and other unusual metastatic sites.
Quality and Safety in Healthcare, Part LVI
Authors: Harolds Jay A.
Published: July 2019

All members of the healthcare system should make positive contributions to improve the overall level of wellness. However, leaders should have certain specific responsibilities to prevent burnout and increase happiness and wellness at work. It has been proposed that a chief wellness officer direct the initiatives to improve wellness, in collaboration with many others including those in the executive suite. Part of improving joy in the workplace is improving efficiency, quality care for patients, safety for patients and workers, meaningful work for the workers, and respect and fairness for all.
Leptomeningeal Metastasis in Carotid Body Paraganglioma
Authors: Tripathy Sarthak , Damle Nishikant Avinash , Naranje Priyanka , Shamim Shamim Ahmed , Tripathi Madhavi , Bal Chandrasekhar
Published: July 2019

Carotid body paragangliomas are mostly benign tumors with very rare propensity to metastasize to lymph nodes, bones, liver, and lungs. Leptomeningeal metastasis from a carotid body paraganglioma is a very rare phenomenon. We describe 68Ga-DOTANOC PET-CT findings of a 33-year-old man, a known case of metastatic paraganglioma who underwent scan for response assessment to everolimus therapy.
A Systematic Review of Behavioral Interventions to Decrease Opioid Prescribing After Surgery
Authors: Zhang David D. Q. , Sussman Jess , Dossa Fahima , Jivraj Naheed , Ladha Karim , Brar Sav , Urbach David , Tricco Andrea C. , Wijeysundera Duminda N. , Clarke Hance A. , Baxter Nancy N.
Published: July 2019

Objective:

The aim of this study was to summarize strategies to reduce postsurgical opioid prescribing at discharge.

Summary Background Data:

Current practices for the prescription of opioids at discharge after surgery are highly variable and often excessive. We conducted a systematic review to identify behavioral interventions designed to improve these practices.

Methods:

We searched MEDLINE, EMBASE, CINAHL, and PsycINFO until December 14, 2018 to identify studies of behavioral interventions designed to decrease opioid prescribing at discharge among adults undergoing surgery. Behavioral interventions were defined according to the Cochrane Effective Practice and Organisation of Care (EPOC) taxonomy. We assessed the risk of bias of included studies using criteria suggested by Cochrane EPOC and the Newcastle-Ottawa scale.

Results:

Of 8048 citations that were screened, 24 studies were included in our review. Six types of behavioral interventions were identified: local consensus-based processes (18 studies), patient-mediated interventions (2 studies), clinical practice guidelines (1 study), educational meetings (1 study), interprofessional education (1 study), and clinician reminder (1 study). All but one study reported a statistically significant decrease in the amount of opioid prescribed at discharge after surgery, and only 2 studies reported evidence of increased pain intensity. Reductions in prescribed opioids ranged from 34.4 to 212.3 mg morphine equivalents. All studies were found to have medium-to-high risks of bias.

Conclusions:

We identified 6 types of behavioral strategies to decrease opioid prescription at discharge after surgery. Despite the risk of bias, almost all types of intervention seemed effective in reducing opioid prescriptions at discharge after surgery without negatively impacting pain control.
Management of Pneumoperitoneum
Authors: Udelsman Brooks , Lee Katherine , Qadan Motaz , Lillemoe Keith D. , Chang David , Lindvall Charlotta , Cooper Zara
Published: July 2019

Objectives:

The aim of this study was to compare morbidity and mortality between nonoperative and operative treatment of pneumoperitoneum.

Background:

Pneumoperitoneum is a potentially life-threatening condition that has been traditionally treated with surgical intervention. Adequately powered studies comparing treatment outcomes are lacking.

Methods:

Chart review and computer-assisted abstraction were used to identify patients with pneumoperitoneum at 5 hospitals from 2010 to 2015. Patients with recent abdominal procedures or contained perforation were excluded. Patients were grouped by treatment modality: comfort measures only (CMO), nonoperative treatment, or operative intervention. CMO included only symptom-palliation, whereas nonoperative therapy included all interventions (antibiotics, peritoneal drains, resuscitation) excluding surgery. Outcomes were mortality, discharge disposition, and 30-day complications. Covariates included demographics, comorbidities, and acuity at presentation.

Results:

Forty patients received CMO, 202 underwent nonoperative treatment, and 199 underwent operative intervention. CMO patients had 98% 30-day mortality. There was no difference in 30-day (P = 0.64) or 2-year mortality (P = 0.53) between patients treated nonoperatively and operatively. Compared with patients treated operatively, patients treated nonoperatively were more likely to have a colorectal source of pneumoperitoneum (37% vs 31%; P = 0.03). Using logistic regression, operative treatment was associated with increased dependence on enteral tube feeding or total parenteral nutrition [odds ratio (OR) 4.30, 95% confidence interval (CI), 1.99–9.29] and nonhome discharge (OR 3.61, 95% CI, 1.81–7.17). Among patients with clinical peritonitis, operative treatment was associated with reduced mortality (OR 0.17, 95% CI, 0.04–0.80).

Conclusions:

Operative intervention is associated with reduced mortality in patients with pneumoperitoneum and peritonitis. In the absence of peritonitis, operative treatment is associated with increased morbidity and nonhome discharge.
Living with cancer and multimorbidity: the role of primary care
Authors: Blane David N. , Lewandowska Marta
Published: July 2019

Purpose of review

As more people live longer with cancer, the number of patients with cancer and multiple other chronic conditions (multimorbidity) has increased. The presence of multimorbidity impacts on all stages of cancer care, from prevention and early detection through to end of life care, but research into cancer and multimorbidity is in its infancy. This review explores the impact of multimorbidity on adults living with (and beyond) cancer, with particular attention paid to the role of primary care in supporting patients in this situation.

Recent findings

Patterns of multimorbidity vary depending on cancer type and stage, as well as population characteristics and available data (e.g. number of conditions assessed). Cancer survivors are at increased risk of developing other chronic conditions, due to a combination of shared risk factors (e.g. smoking and obesity), effects of cancer treatments and psychosocial effects.

Primary care has a central role to play in supporting multimorbid adults living with cancer, providing holistic care of physical and mental well being, while taking treatment burden and social circumstances into account. New models of person-centred and personalized cancer care include holistic needs assessments, care planning, treatment summaries and cancer care reviews, and depend on improved communication between oncologists and primary care colleagues.
Hypothermia Associated With Melatonin Ingestion in a Child With Autism
Authors: Erden Semih
Published: July 2019

Autism spectrum disorder is a neurodevelopmental disorder characterized by social interaction and communication disorder and restrictive and repetitive behaviors. Sleep disorders are frequently observed in children with autism spectrum disorder. We present a case of hypothermia in an autistic child with a sleep disorder whose body temperature decreased to 34°C after a single dose of melatonin. Hypothermia continued for 2 more days, but her nighttime sleeping problems decreased. This case is important because it demonstrates the possible risk of hypothermia with melatonin use in children with autism with a sleep disorder.
Risk Factors of Relapse After Successful Electroconvulsive Therapy for Taiwanese Patients With Major Depression
Authors: Yang Wei-Cheng , Lin Ching-Hua , Chen Cheng-Chung
Published: July 2019

Objectives

Major depressive disorder is a recurrent illness. Treatment strategies are generally focused on achieving remission and preventing relapse/recurrence. The aim of this study was to explore the risk factors associated with relapse for remitted patients during the 12-week follow-up.

Methods

This was an open-label trial for major depressive disorder patients receiving acute treatments with electroconvulsive therapy (ECT) and continuation medication in the 12-week follow-up. Symptom severity and psychosocial functioning were assessed using the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the Work and Social Adjustment Scale at each visit. Remission was defined as a HAMD-17 of 7 or less after acute treatment. Relapse was defined as a HAMD-17 of 14 or greater. Subjects achieving remission after acute treatments were included for analysis. Survival analysis was used to investigate the factors associated with relapse.

Results

Sixty patients receiving ECT for acute treatment were enrolled for 12-week follow-up. Using Cox regression analysis, a greater number of previous major depressive episodes and greater baseline Work and Social Adjustment Scale scores were significantly associated with shorter time to relapse.

Conclusions

The goal of acute treatment should focus on functional remission to prevent relapse. Further studies related to more effective treatments to prevent relapse after acute ECT are required in the future.
The development of methodology and techniques for crop disease identification
Authors: Tiwari N. S. , Richmond J. W.
Published: July 2019

In India, an estimated 15-25% of potential crop production is lost due pest and diseases (Roy and Bezbaruah, 2002). The country needs not only to raise production but also ensure food security for its growing consumption needs while curbing excessive pesticide usage. Detection of pests and diseases at an early stage plays a significant role in addressing the above-mentioned concerns and image classification offers a cost-effective and scalable solution to the disease detection problem (A. Ramcharan et al. 2017). Here, the principles of transfer learning are implemented with pretrained model – Resnet34 (K. He et al. 2015), and test its effectiveness in image classification using a dataset of tea leaves. The novelty of this work is that the images used are not curated, individual leaves with controlled backgrounds but of plants in-situ. The effect of the level of zoom and background is examined and class activation maps are used to validate that the basis of classification is indeed the disease and not an artificial bias from factors such as background, lighting etc.
Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS
Authors: Waters Sarah , Dieriks Birger V. , Swanson Molly E. V. , Zhang Yibin , Grimsey Natasha L. , Murray Helen C. , Turner Clinton , Waldvogel Henry J. , Faull Richard L.M. , An Jiyan , Bowser Robert , Curtis Maurice A. , Dragunow Mike , Scotter Emma L.
Published: July 2019

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. Both lower motor neuron loss and the deposition of phosphorylated TDP-43 inclusions display regional patterning along the spinal cord. The blood-spinal cord barrier (BSCB) ordinarily restricts entry into the spinal cord parenchyma of blood components that are neurotoxic, but in ALS there is evidence for barrier breakdown. Here we sought to examine whether BSCB breakdown, motor neuron loss, and TDP-43 proteinopathy display the same regional patterning across and along the spinal cord.

Methods

We measured cerebrospinal fluid (CSF) hemoglobin in living ALS patients (n=87 controls, n=236 ALS) as a potential biomarker of BSCB and blood-brain barrier leakage. We then immunostained cervical, thoracic, and lumbar post mortem spinal cord tissue (n=5 controls, n=13 ALS) and employed semi-automated imaging and analysis to quantify and map lower motor neuron loss and phosphorylated TDP-43 inclusion load against hemoglobin leakage.

Results

Motor neuron loss and TDP-43 proteinopathy were seen at all three levels of the ALS spinal cord, with most abundant TDP-43 deposition in the ventral grey (lamina IX) of the cervical and lumbar cord. In contrast, hemoglobin leakage was observed along the ALS spinal cord axis but was most severe in the dorsal grey and white matter in the thoracic spinal cord.

Conclusions

Our data show that leakage of the blood-spinal cord barrier occurs during life but at end-stage its distribution is independent from the major motor neuron pathology and is unlikely to be a major contributor to pathogenesis in ALS.
Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework
Authors: Brnich Sarah E. , Abou Tayoun Ahmad N. , Couch Fergus J. , Cutting Garry R. , Greenblatt Marc S. , Heinen Christopher D. , Kanavy Dona M. , Luo Xi , McNulty Shannon M. , Starita Lea M. , Tavtigian Sean V. , Wright Matt W. , Harrison Steven M. , Biesecker Leslie G. , Berg Jonathan S. ,   On behalf of the Clinical Genome Resource Sequence Variant Interpretation Working Group
Published: July 2019

Background

The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) clinical variant interpretation guidelines established criteria (PS3/BS3) for functional assays that specified a “strong” level of evidence. However, they did not provide detailed guidance on how functional evidence should be evaluated, and differences in the application of the PS3/BS3 codes is a contributor to variant interpretation discordance between laboratories. This recommendation seeks to provide a more structured approach to the assessment of functional assays for variant interpretation and guidance on the use of various levels of strength based on assay validation.

Methods

The Clinical Genome Resource (ClinGen) Sequence Variant Interpretation (SVI) Working Group used curated functional evidence from ClinGen Variant Curation Expert Panel-developed rule specifications and expert opinions to refine the PS3/BS3 criteria over multiple in-person and virtual meetings. We estimated odds of pathogenicity for assays using various numbers of variant controls to determine the minimum controls required to reach moderate level evidence. Feedback from the ClinGen Steering Committee and outside experts were incorporated into the recommendations at multiple stages of development.

Results

The SVI Working Group developed recommendations for evaluators regarding the assessment of the clinical validity of functional data and a four-step provisional framework to determine the appropriate strength of evidence that can be applied in clinical variant interpretation. These steps are: 1. Define the disease mechanism; 2. Evaluate applicability of general classes of assays used in the field; 3. Evaluate validity of specific instances of assays; 4. Apply evidence to individual variant interpretation. We found that a minimum of eleven total pathogenic and benign variant controls are required to reach moderate-level evidence in the absence of rigorous statistical analysis.

Conclusions

The recommendations and approach to functional evidence evaluation described here should help clarify the clinical variant interpretation process for functional assays. Further, we hope that these recommendations will help develop productive partnerships with basic scientists who have developed functional assays that are useful for interrogating the function of a variety of genes.
A mini-atlas of gene expression for the domestic goat (Capra hircus) reveals transcriptional differences in immune signatures between sheep and goats
Authors: Muriuki Charity , Bush Stephen J. , Salavati Mazdak , McCulloch Mary E.B. , Lisowski Zofia M. , Agaba Morris , Djikeng Appolinaire , Hume David A. , Clark Emily L.
Published: July 2019

Goats (Capra hircus) are an economically important livestock species providing meat and milk across the globe. They are of particular importance in tropical agri-systems contributing to sustainable agriculture, alleviation of poverty, social cohesion and utilisation of marginal grazing. There are excellent genetic and genomic resources available for goats, including a highly contiguous reference genome (ARS1). However, gene expression information is limited in comparison to other ruminants. To support functional annotation of the genome and comparative transcriptomics we created a mini-atlas of gene expression for the domestic goat. RNA-Seq analysis of 22 transcriptionally rich tissues and cell-types detected the majority (90%) of predicted protein-coding transcripts and assigned informative gene names to more than 1000 previously unannotated protein-coding genes in the current reference genome for goat (ARS1). Using network-based cluster analysis we grouped genes according to their expression patterns and assigned those groups of co-expressed genes to specific cell populations or pathways. We describe clusters of genes expressed in the gastro-intestinal tract and provide the expression profiles across tissues of a subset of genes associated with functional traits. Comparative analysis of the goat atlas with the larger sheep gene expression atlas dataset revealed transcriptional differences between the two species in macrophage-associated signatures. The goat transcriptomic resource complements the large gene expression dataset we have generated for sheep and contributes to the available genomic resources for interpretation of the relationship between genotype and phenotype in small ruminants.
Cholesterol and matrisome pathways dysregulated in human APOE ε4 glia
Authors: TCW Julia , Liang Shuang A. , Qian Lu , Pipalia Nina H , Chao Michael J. , Shi Yang , Bertelsen Sarah E. , Kapoor Manav , Marcora Edoardo , Sikora Elizabeth , Holtzman David M. , Maxfield Frederick R. , Zhang Bin , Wang Minghui , Poon Wayne W. , Goate Alison M.
Published: July 2019

Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer’s disease (AD). Although its association with AD is well-established, the impact of APOE ε4 on human brain cell function remains unclear. Here we investigated the effects of APOE ε4 on several brain cell types derived from human induced pluripotent stem cells and human APOE targeted replacement mice. Gene set enrichment and pathway analyses of whole transcriptome profiles showed that APOE ε4 is associated with dysregulation of cholesterol homeostasis in human but not mouse astrocytes and microglia. Elevated matrisome signaling associated with chemotaxis, glial activation and lipid biosynthesis in APOE ε4 mixed neuron/astrocyte cultures parallels altered pathways uncovered in cell-type deconvoluted transcriptomic data from APOE ε4 glia and AD post-mortem brains. Experimental validation of the transcriptomic findings showed that isogenic APOE ε4 is associated with increased lysosomal cholesterol levels and decreased cholesterol efflux, demonstrating decoupled lipid metabolism. APOE ε4 glia also secrete higher levels of proinflammatory chemokines, cytokines and growth factors, indicative of glial activation. Thus, APOE ε4 induces human glia-specific dysregulation that may initiate AD risk.
Automating Three-dimensional Osteoarthritis Histopathological Grading of Human Osteochondral Tissue using Machine Learning on Contrast-Enhanced Micro-Computed Tomography
Authors: Rytky S.J.O. , Tiulpin A. , Frondelius T. , Finnilä M.A.J. , Karhula S.S. , Leino J. , Pritzker K.P.H. , Valkealahti M. , Lehenkari P. , Joukainen A. , Kröger H. , Nieminen H.J. , Saarakkala S.
Published: July 2019

Objective

To develop and validate a machine learning (ML) approach for automatic three-dimensional (3D) histopathological grading of osteochondral samples imaged with contrast-enhanced micro-computed tomography (CEμCT).

Design

Osteochondral cores from 24 total knee arthroplasty patients and 2 asymptomatic cadavers (n = 34, Ø = 2 mm; n = 45, Ø = 4 mm) were imaged using CEμCT with phosphotungstic acid-staining. Volumes-of-interest (VOI) in surface (SZ), deep (DZ) and calcified (CZ) zones were extracted depthwise and subjected to dimensionally reduced Local Binary Pattern-textural feature analysis. Regularized Ridge and Logistic regression (LR) models were trained zone-wise against the manually assessed semi-quantitative histopathological CEμCT grades (Ø = 2 mm samples). Models were validated using nested leave-one-out cross-validation and an independent test set (Ø = 4 mm samples). The performance was assessed using Spearman’s correlation, Average Precision (AP) and Area under the Receiver Operating Characteristic Curve (AUC).

Results

Highest performance on cross-validation was observed for SZ, both on Ridge regression (ρ = 0.68, p < 0.0001) and LR (AP = 0.89, AUC = 0.92). The test set evaluations yielded decreased Spearman’s correlations on all zones. For LR, performance was almost similar in SZ (AP = 0.89, AUC = 0.86), decreased in CZ (AP = 0.71→0.62, AUC = 0.77→0.63) and increased in DZ (AP = 0.50→0.83, AUC = 0.72→0.72).

Conclusion

We showed that the ML-based automatic 3D histopathological grading of osteochondral samples is feasible from CEμCT. The developed method can be directly applied by OA researchers since the grading software and all source codes are publicly available.
Improving yield and fruit quality traits in sweet passion fruit: evidence for genotype by environment interaction and cross-compatibility in selected genotypes
Authors: Chavarría-Perez Lourdes Maria , Giordani Willian , das Graças Dias Kaio Olimpio , da Costa Zirlane Portugal , Ribeiro Carolina Albuquerque Massena , Benedetti Anderson Roberto , Cauz-Santos Luiz Augusto , da Silva Pereira Guilherme , Rosa João Ricardo Bachega Feijó , Garcia Antonio Augusto Franco , Vieira Maria Lucia Carneiro
Published: July 2019

Breeding for yield and fruit quality traits in passion fruits is complex due to the polygenic nature of these traits and the existence of genetic correlations among them. Therefore, studies focused on crop management practices and breeding using modern quantitative genetic approaches are still needed, especially for Passiflora alata, an understudied crop, popular known as the sweet passion fruit. It is assumed to be a self-incompatible species and is highly appreciated for its typical aroma and flavor characteristics. With the aim of estimating the genetic and phenotypic parameters related to fruit traits, our group has already investigated a sweet passion fruit progeny consisting of 100 individuals from which 30 genotypes were selected. In this study, we reevaluated these superior genotypes in three environmental conditions. The results of the multi-environment trial analysis indicate that the genotypes do not behave consistently across these environments, and this was taken into account when selecting genotypes. Pairwise genetic correlations among the fruit traits were evaluated, and different genotype rankings obtained depending on the trait and environment, providing further evidence of genotype by environment interaction. Finally, we used a multiplicative selection index to select 20% of genotypes for weight of pulp and against thickness and weight of the fruit skin. The response to selection was positive for all traits except soluble solids, and the superior (six) genotypes were ranked. The consensus is that open-pollinated populations can be used as commercial varieties in crop species that are sensitive to inbreeding depression or within breeding programs that are not well developed. For these reasons, we performed a complete diallel cross for evaluating the capability of the selected genotypes to be fertilized and set fruits. Most of the crosses were compatible, resulting in over 50% fruit set. It is worth noting that all genotypes produce fruits if used as females, which is essential to guarantee yields in commercial orchards.