Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LVT) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA). The LVT approach attempts to protect already open lung tissue from overdistension, while simultaneously resting collapsed tissue by excluding it from the cycle of mechanical ventilation. By contrast, the OLA attempts to reinflate potentially recruitable lung, usually over a period of seconds to minutes using higher PEEP used to prevent progressive loss of end-expiratory lung volume (EELV) and RACE. However, even with these protective strategies, clinical studies have shown that ARDS-related mortality remains unacceptably high with a scarcity of effective interventions over the last two decades. One of the main limitations these varied interventions demonstrate to benefit is the observed clinical and pathologic heterogeneity in ARDS. We have developed an alternative ventilation strategy known as the Time Controlled Adaptive Ventilation (TCAV) method of applying the Airway Pressure Release Ventilation (APRV) mode, which takes advantage of the heterogeneous time- and pressure-dependent collapse and reopening of lung units. The TCAV method is a closed-loop system where the expiratory duration personalizes VT and EELV. Personalization of TCAV is informed and tuned with changes in respiratory system compliance (CRS) measured by the slope of the expiratory flow curve during passive exhalation. Two potentially beneficial features of TCAV are: (i) the expiratory duration is personalized to a given patient's lung physiology, which promotes alveolar stabilization by halting the progressive collapse of alveoli, thereby minimizing the time for the reopened lung to collapse again in the next expiration, and (ii) an extended inspiratory phase at a fixed inflation pressure after alveolar stabilization gradually reopens a small amount of tissue with each breath. Subsequently, densely collapsed regions are slowly ratcheted open over a period of hours, or even days. Thus, TCAV has the potential to minimize VILI, reducing ARDS-related morbidity and mortality.

Airway pressure release ventilation for lung protection in acute respiratory distress syndrome: an alternative way to recruit the lungs.

PURPOSE OF REVIEW: Airway pressure release ventilation (APRV) is a modality of ventilation in which high inspiratory continuous positive airway pressure (CPAP) alternates with brief releases. In this review, we will discuss the rationale for APRV as a lung protective strategy and then provide a practical introduction to initiating APRV using the time-controlled adaptive ventilation (TCAV) method. RECENT FINDINGS: APRV using the TCAV method uses an extended inspiratory time and brief expiratory release to first stabilize and then gradually recruit collapsed lung (over hours/days), by progressively 'ratcheting' open a small volume of collapsed tissue with each breath. The brief expiratory release acts as a 'brake' preventing newly recruited units from re-collapsing, reversing the main drivers of ventilator-induced lung injury (VILI). The precise timing of each release is based on analysis of expiratory flow and is set to achieve termination of expiratory flow at 75% of the peak expiratory flow. Optimization of the release time reflects the changes in elastance and, therefore, is personalized (i.e. conforms to individual patient pathophysiology), and adaptive (i.e. responds to changes in elastance over time). SUMMARY: APRV using the TCAV method is a paradigm shift in protective lung ventilation, which primarily aims to stabilize the lung and gradually reopen collapsed tissue to achieve lung homogeneity eliminating the main mechanistic drivers of VILI.

Design, synthesis, molecular docking and biological evaluation of 1,3,5-trisubstituted-1H-pyrazole derivatives as anticancer agents with cell cycle arrest, ERK and RIPK3- kinase activities.

The need for new ERK and RIPK3 kinase modulators arises from their central roles in cellular processes, especially in diseases like cancer. This research focused on a ligand-based strategy, incorporating previously documented 1,3,5-trisubstituted-1H-pyrazole derivatives, to craft innovative inhibitors specifically targeting ERK and RIPK3 kinases. Compounds 6, 7, 10a, 10c, and 10d exhibited significant cytotoxicity against PC-3 and MCF-7 cancer cell lines, with IC50 values ranging from 21.9 to 28.6 µM and 3.90-35.5 µM, respectively values surpassing those of the reference compound Doxorubicin. Additionally, cell cycle analysis revealed intriguing results, particularly with 10d inducing cell cycle arrest at the S phase in treated PC-3 cells, indicating potential DNA replication phase inhibition. Moreover, compounds 6, 10a, and 10d exhibited promising results in the in vitro kinase assay supported by molecular docking studies. The core scaffold of these compounds established interactions with vital amino acids within the active pockets of ERK and RIPK3 kinases, thereby securely anchoring them in place. These findings underscore the development of promising modulators for ERK and RIPK3 kinases, suggesting their potential for future contributions to cancer treatments.

SAGES peritoneal dialysis access guideline update 2023.

BACKGROUND: Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed. RESULTS: After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction. CONCLUSIONS: In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.

SAGES guidelines for the surgical treatment of hiatal hernias.

BACKGROUND: Hiatal hernia (HH) is a common condition. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of HH. METHODS: Systematic reviews were conducted for four key questions regarding the treatment of HH in adults: surgical treatment of asymptomatic HH versus surveillance; use of mesh versus no mesh; performing a fundoplication versus no fundoplication; and Roux-en-Y gastric bypass (RYGB) versus redo fundoplication for recurrent HH. Evidence-based recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations methodology by subject experts. When the evidence was insufficient to base recommendations on, expert opinion was utilized instead. Recommendations for future research were also proposed. RESULTS: The panel provided one conditional recommendation and two expert opinions for adults with HH. The panel suggested routinely performing a fundoplication in the repair of HH, though this was based on low certainty evidence. There was insufficient evidence to make evidence-based recommendations regarding surgical repair of asymptomatic HH or conversion to RYGB in recurrent HH, and therefore, only expert opinions were offered. The panel suggested that select asymptomatic patients may be offered surgical repair, with criteria outlined. Similarly, it suggested that conversion to RYGB for management of recurrent HH may be appropriate in certain patients and again described criteria. The evidence for the routine use of mesh in HH repair was equivocal and the panel deferred making a recommendation. CONCLUSIONS: These recommendations should provide guidance regarding surgical decision-making in the treatment of HH and highlight the importance of shared decision-making and consideration of patient values to optimize outcomes. Pursuing the identified research needs will improve the evidence base and may allow for stronger recommendations in future evidence-based guidelines for the treatment of HH.

SAGES guideline for the diagnosis and treatment of appendicitis.

BACKGROUND: Appendicitis is an extremely common disease with a variety of medical and surgical treatment approaches. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians and patients in decisions regarding the diagnosis and treatment of appendicitis. METHODS: A systematic review was conducted from 2010 to 2022 to answer 8 key questions relating to the diagnosis of appendicitis, operative or nonoperative management, and specific technical and post-operative issues for appendectomy. The results of this systematic review were then presented to a panel of adult and pediatric surgeons. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. RESULTS: Conditional recommendations were made in favor of uncomplicated and complicated appendicitis being managed operatively, either delayed (>12h) or immediate operation (<12h), either suction and lavage or suction alone, no routine drain placement, treatment with short-term antibiotics postoperatively for complicated appendicitis, and complicated appendicitis previously treated nonoperatively undergoing interval appendectomy. A conditional recommendation signals that the benefits of adhering to a recommendation probably outweigh the harms although it does also indicate uncertainty. CONCLUSIONS: These recommendations should provide guidance with regard to current controversies in appendicitis. The panel also highlighted future research opportunities where the evidence base can be strengthened.

Management of symptomatic, asymptomatic, and recurrent hiatal hernia: a systematic review and meta-analysis.

BACKGROUND: The surgical management of hiatal hernia remains controversial. We aimed to compare outcomes of mesh versus no mesh and fundoplication versus no fundoplication in symptomatic patients; surgery versus observation in asymptomatic patients; and redo hernia repair versus conversion to Roux-en-Y reconstruction in recurrent hiatal hernia. METHODS: We searched PubMed, Embase, CINAHL, Cochrane Library and the ClinicalTrials.gov databases between 2000 and 2022 for randomized controlled trials (RCTs), observational studies, and case series (asymptomatic and recurrent hernias). Screening was performed by two trained independent reviewers. Pooled analyses were performed on comparative data. Risk of bias was assessed using the Cochrane Risk of Bias tool and Newcastle Ottawa Scale for randomized and non-randomized studies, respectively. RESULTS: We included 45 studies from 5152 retrieved records. Only six RCTs had low risk of bias. Mesh was associated with a lower recurrence risk (RR = 0.50, 95%CI 0.28, 0.88; I2 = 57%) in observational studies but not RCTs (RR = 0.98, 95%CI 0.47, 2.02; I2 = 34%), and higher total early dysphagia based on five observational studies (RR = 1.44, 95%CI 1.10, 1.89; I2 = 40%) but was not statistically significant in RCTs (RR = 3.00, 95%CI 0.64, 14.16). There was no difference in complications, reintervention, heartburn, reflux, or quality of life. There were no appropriate studies comparing surgery to observation in asymptomatic patients. Fundoplication resulted in higher early dysphagia in both observational studies and RCTs ([RR = 2.08, 95%CI 1.16, 3.76] and [RR = 20.58, 95%CI 1.34, 316.69]) but lower reflux in RCTs (RR = 0.31, 95%CI 0.17, 0.56, I2 = 0%). Conversion to Roux-en-Y was associated with a lower reintervention risk after 30 days compared to redo surgery. CONCLUSIONS: The evidence for optimal management of symptomatic and recurrent hiatal hernia remains controversial, underpinned by studies with a high risk of bias. Shared decision making between surgeon and patient is essential for optimal outcomes.

Synthesis of the chromone-thiosemicarbazone scaffold as promising α-glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design.

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC50 value of 0.40 ± 0.02 µM, ~2183-fold higher than acarbose having an IC50 of 873.34 ± 1.67 µM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase.

Best Practices for Measuring the Modulation Transfer Function of Video Endoscopes.

Endoscopes are crucial for assisting in surgery and disease diagnosis, including the early detection of cancer. The effective use of endoscopes relies on their optical performance, which can be characterized with a series of metrics such as resolution, vital for revealing anatomical details. The modulation transfer function (MTF) is a key metric for evaluating endoscope resolution. However, the 2020 version of the ISO 8600-5 standard, while introducing an endoscope MTF measurement method, lacks empirical validation and excludes opto-electronic video endoscopes, the largest family of endoscopes. Measuring the MTF of video endoscopes requires tailored standards that address their unique characteristics. This paper aims to expand the scope of ISO 8600-5:2020 to include video endoscopes, by optimizing the MTF test method and addressing parameters affecting measurement accuracy. We studied the effects of intensity and uniformity of image luminance, chart modulation compensation, linearity of image digital values, auto gain control, image enhancement, image compression and the region of interest dimensions on images of slanted-edge test charts, and thus the MTF based on these images. By analyzing these effects, we provided recommendations for setting and controlling these factors to obtain accurate MTF curves. Our goal is to enhance the standard's relevance and effectiveness for measuring the MTF of a broader range of endoscopic devices, with potential applications in the MTF measurement of other digital imaging devices.

Diagnosis and treatment of appendicitis: systematic review and meta-analysis.

BACKGROUND: The optimal diagnosis and treatment of appendicitis remains controversial. This systematic review details the evidence and current best practices for the evaluation and management of uncomplicated and complicated appendicitis in adults and children. METHODS: Eight questions regarding the diagnosis and management of appendicitis were formulated. PubMed, Embase, CINAHL, Cochrane and clinicaltrials.gov/NLM were queried for articles published from 2010 to 2022 with key words related to at least one question. Randomized and non-randomized studies were included. Two reviewers screened each publication for eligibility and then extracted data from eligible studies. Random effects meta-analyses were performed on all quantitative data. The quality of randomized and non-randomized studies was assessed using the Cochrane Risk of Bias 2.0 or Newcastle Ottawa Scale, respectively. RESULTS: 2792 studies were screened and 261 were included. Most had a high risk of bias. Computerized tomography scan yielded the highest sensitivity (> 80%) and specificity (> 93%) in the adult population, although high variability existed. In adults with uncomplicated appendicitis, non-operative management resulted in higher odds of readmission (OR 6.10) and need for operation (OR 20.09), but less time to return to work/school (SMD - 1.78). In pediatric patients with uncomplicated appendicitis, non-operative management also resulted in higher odds of need for operation (OR 38.31). In adult patients with complicated appendicitis, there were higher odds of need for operation following antibiotic treatment only (OR 29.00), while pediatric patients had higher odds of abscess formation (OR 2.23). In pediatric patients undergoing appendectomy for complicated appendicitis, higher risk of reoperation at any time point was observed in patients who had drains placed at the time of operation (RR 2.04). CONCLUSIONS: This review demonstrates the diagnosis and treatment of appendicitis remains nuanced. A personalized approach and appropriate patient selection remain key to treatment success. Further research on controversies in treatment would be useful for optimal management.

Effect of Systolic and Diastolic Blood Pressure on Cardiovascular Outcomes.

BACKGROUND: The relationship between outpatient systolic and diastolic blood pressure and cardiovascular outcomes remains unclear and has been complicated by recently revised guidelines with two different thresholds (≥140/90 mm Hg and ≥130/80 mm Hg) for treating hypertension. METHODS: Using data from 1.3 million adults in a general outpatient population, we performed a multivariable Cox survival analysis to determine the effect of the burden of systolic and diastolic hypertension on a composite outcome of myocardial infarction, ischemic stroke, or hemorrhagic stroke over a period of 8 years. The analysis controlled for demographic characteristics and coexisting conditions. RESULTS: The burdens of systolic and diastolic hypertension each independently predicted adverse outcomes. In survival models, a continuous burden of systolic hypertension (≥140 mm Hg; hazard ratio per unit increase in z score, 1.18; 95% confidence interval [CI], 1.17 to 1.18) and diastolic hypertension (≥90 mm Hg; hazard ratio per unit increase in z score, 1.06; 95% CI, 1.06 to 1.07) independently predicted the composite outcome. Similar results were observed with the lower threshold of hypertension (≥130/80 mm Hg) and with systolic and diastolic blood pressures used as predictors without hypertension thresholds. A J-curve relation between diastolic blood pressure and outcomes was seen that was explained at least in part by age and other covariates and by a higher effect of systolic hypertension among persons in the lowest quartile of diastolic blood pressure. CONCLUSIONS: Although systolic blood-pressure elevation had a greater effect on outcomes, both systolic and diastolic hypertension independently influenced the risk of adverse cardiovascular events, regardless of the definition of hypertension (≥140/90 mm Hg or ≥130/80 mm Hg). (Funded by the Kaiser Permanente Northern California Community Benefit Program.).

Incidence, Timing, and Outcomes of Venous Thromboembolism in Patients Undergoing Surgery for Esophagogastric Cancer: A Population-Based Cohort Study.

BACKGROUND: Abdominal surgery and chemotherapy are well-established risk factors for venous thromboembolism (VTE) in patients with cancer, but their specific contribution in patients with esophageal and gastric cancer is unclear. We aim to quantify the risk of VTE, identify risk factors associated with VTE, and determine the association between VTE and survival in patients undergoing surgery for esophageal or gastric cancer. METHODS: A retrospective, population-based cohort study was conducted using linked administrative healthcare databases. We used the Ontario Cancer Registry to identify patients with esophageal or gastric cancer between January 1, 2007 and December 31, 2016 who underwent surgical resection. Incidence of first VTE event was identified using International Classification of Diseases 9 and 10 codes. VTE incidence was calculated at clinically relevant time points 180 days before and after surgery. Logistic regression was used to identify factors associated with VTE with odds ratios (OR) and 95% confidence intervals (CI) reported. Cox proportional hazards regression models were used to estimate associations between covariates and survival. Kaplan-Meier method was used to compare overall (OS) and cancer-specific survival (CSS) by VTE status. RESULTS: A total of 4894 patients had esophagectomy or gastrectomy, of which 8% (n = 383/4894) had VTE. VTE risk was 2.5% (n = 123/4894) 180 days before surgery, 2.8% (n = 138/4894) within 30 days of surgery, and 2.5% (n = 122/4894) from 31 to ≤ 180 days after surgery. Of the patients with VTE within 30 days of surgery, 34% (n = 47/138) were diagnosed after discharge from hospital. Receipt of preoperative chemotherapy was associated with VTE 180 days before surgery (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.41, 6.11). Increased hospital length of stay (LOS) was associated with VTE 30 days after surgery (OR 1.08, 95% CI 1.02, 1.14, per week). Patients with VTE had inferior median OS and CSS (2.2 vs. 3.7 years; 2.3 vs. 4.4 years, respectively). In adjusted models VTE was associated with inferior OS (HR 1.36, 95% CI 1.13, 1.63) and CSS (HR 1.42, 95% CI 1.16, 1.75). CONCLUSIONS: The highest risk of VTE is within 30 days of surgery with one third of patients diagnosed after discharge from hospital. Longer hospital LOS and receipt of preoperative chemotherapy are associated with increased risk of VTE. VTE is an independent risk factor for inferior survival in patients with esophageal or gastric cancer.

Comparative pathogenesis of turkey reoviruses.

Turkey reoviruses have been implicated in multiple disease syndromes resulting in significant economic losses to the turkey industry. It has been known for decades that turkey enteric reovirus (TERV) is involved in poult enteritis complex, but turkey arthritis reovirus (TARV), the causative agent of tenosynovitis in turkeys, emerged in 2011. In 2019, we isolated reovirus from several cases of hepatitis in turkeys and tentatively named it turkey hepatitis reovirus (THRV). The comparative pathogenesis of these viruses, and correlation with their genetic make-up (if any), is not known. In this study, we inoculated nine groups of 1-week-old turkey poults with two THRV, five TARV and two TERV via oral route. A tenth group served as a negative control. A subset of birds from each group was euthanised at 3, 5, 7, 14, 21, and 28 days post-inoculation (dpi). Tissues were collected for histology and real-time RT-PCR. All nine viruses were found to be enterotropic; the virus gene copy number in the intestine reached a peak at 5 dpi followed by a sharp decline at 7 dpi. All viruses caused a significant decline in body weight gain of birds as compared to the negative control group. Both TARV and THRV strains replicated in tendons and produced histologic lesions consistent with tenosynovitis. Hepatic lesions were produced by THRV only and the virus was re-isolated from liver and spleen of inoculated birds fulfilling Koch's postulates. The results of this study should be helpful in facilitating diagnosis and designing future mitigation plans.

Unshrinking the baby lung to calm the VILI vortex.

A hallmark of ARDS is progressive shrinking of the 'baby lung,' now referred to as the ventilator-induced lung injury (VILI) 'vortex.' Reducing the risk of the VILI vortex is the goal of current ventilation strategies; unfortunately, this goal has not been achieved nor has mortality been reduced. However, the temporal aspects of a mechanical breath have not been considered. A brief expiration prevents alveolar collapse, and an extended inspiration can recruit the atelectatic lung over hours. Time-controlled adaptive ventilation (TCAV) is a novel ventilator approach to achieve these goals, since it considers many of the temporal aspects of dynamic lung mechanics.

SAGES 2022 guidelines regarding the use of laparoscopy in the era of COVID-19.

BACKGROUND: SARS-CoV-2 has changed global healthcare since the pandemic began in 2020. The safety of minimally invasive surgery (MIS) utilizing insufflation from the standpoint of safety to the operating room personnel is currently being explored. The aims of this guideline are to examine the existing evidence to provide guidance regarding MIS for the patient with, or suspecting of having, the SARS-CoV-2 as well as the healthcare team involved. METHODS: Systematic literature reviews were conducted for 2 key questions (KQ) regarding the safety of MIS in the setting of COVID-19 pandemic. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria. Evidence-based recommendations were formulated using a narrative synthesis of the literature by subject experts. Recommendations for future research were also proposed. RESULTS: In KQ1, a total of 1361 articles were reviewed, with 2 articles meeting inclusion. In KQ2, a total of 977 articles were reviewed, with 4 articles met inclusions criteria, of which 2 studies reported on the SARS-CoV2 virus specifically. Despite many publications in the field, very little well-controlled and unbiased data exist to inform the recommendations. Of that which is available, it shows that both laparoscopic and open operations in Covid-positive patients had similar rates of OR staff positivity rates; however, patients who underwent laparoscopic procedures had a lower perioperative mortality than open procedures. Also, SARS-CoV-2 particles have been detected in the surgical plume at laparoscopy. CONCLUSION: With demonstrated equivalence of operating room staff exposure, and noninferiority of laparoscopic access with respect to mortality, either laparoscopic or open approaches to abdominal operations may be used in patients with SARS-CoV-2. Measures should be employed for all laparoscopic or open cases to prevent exposure of operating room staff to the surgical plume, as virus can be present in this plume.

Discovery of Quinazoline-2,4(1H,3H)-Dione Derivatives as Potential Antibacterial Agent: Design, Synthesis, and Their Antibacterial Activity.

In this paper, we report on the design and synthesis of a novel series of quinazoline-2,4(1H,3H)-dione derivatives as fluoroquinolone-like inhibitors of bacterial gyrase and DNA topoisomerase IV to identify and develop antimicrobial agents to prevent bacterial resistance problems. Their structures were confirmed using spectroscopic analyses (IR, NMR, and EI-MS). The novel quinazoline-2,4(1H,3H)-dione derivatives were evaluated for their antimicrobial activities against Gram-positive and Gram-negative bacterial strains using the Agar well diffusion method to study the antimicrobial activities and compared them with the standard drugs. Most compounds displayed moderate activity. Among the tested compounds, the most promising compounds 13 and 15 provided broad bioactive spectrum against Gram-positive and Gram-negative strains compared to the standard drugs.

Streptococcus, Centrocestus formosanus and Myxobolus tilapiae concurrent infections in farmed Nile tilapia (Oreochromis niloticus).

Stress triggered concurrent microbial/parasitic infections are prevalent in earthen pond based farmed Nile tilapia Oreochromis niloticus. In the current study, a total of thirty five O. niloticus were collected from a commercial fish farm with a history of severe mortalities at Port Said, Egypt. Nile tilapia samples were subjected to bacteriological, parasitological and pathological examinations. Twenty one Enterococcus fecalis and 15 Streptococcus agalactiae isolates were presumptively identified utilizing the semi-automated API 20 Strept test kit. The identities of the retrieved bacteria were confirmed by the sequencing of 16 S rRNA gene. Moribund O. niloticus were found to be heavily infected by one or both of Centrocestus formosanus encysted metacercariae (EMC) and/or Myxobolus tilapiae spores presenting a unique form of synergistic and/or symbiotic relationship. The identities of both parasites were confirmed through morphological and molecular characterization. Variable circulatory, degenerative, necrotic and proliferative changes were also noticed in hematopoietic organs. Interestingly, multiple myxobolus spores and EMC were noticed in some histological sections. It was obvious that the current concurrent bacterial and parasitic infections are triggered by the deleterious effects of some stressing environmental conditions. The unfavorable climatic conditions (high temperature and high relative humidity) recorded at the surge of mortalities are probable predisposing stress factors.

Equivalent tumor detection for early and late FAPI-46 PET acquisition.

INTRODUCTION: Positron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer. METHODS: This is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33). RESULTS: In total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUVmax of hottest tumor lesions (Wilcoxon: P = 0.73). Organ uptake demonstrated significant early to late decrease in SUVmean (average ∆SUVmean: - 0.48, - 0.14, - 0.27 for gluteus, liver, and mediastinum, respectively; Wilcoxon: P < 0.001). On a per-lesion basis, a slight increase of SUVmax was observed (average ∆SUVmax: + 0.4, Wilcoxon: P = 0.03). CONCLUSION: In conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols.

Smartphone addiction and associated factors among postgraduate students in an Arabic sample: a cross-sectional study.

BACKGROUND: Smartphone addiction, as with other behavioral addictions, is associated with social, physical, and mental health issues. In this article, we investigated the prevalence of smartphone addiction among postgraduate students and evaluated its correlation with social demographics, depression, attention-deficit/hyperactivity disorder (ADHD), and nicotine dependence. OBJECTIVES: The objective of this study was to investigate the prevalence of smartphone addiction among Middle Eastern postgraduate students, determine the factors associated with smartphone addiction, and estimate the incidence rate of major depressive disorder (MDD), ADHD, insomnia, and nicotine addiction among postgraduate students with smartphone addiction. METHODS: As part of a cross-sectional online survey, participants were given a self-questionnaire divided into six sections: Socio-demographics, Smartphone Addiction Scale (SAS), Patient Health Questionnaire (PHQ9) for Depression, Athens Insomnia Scale (AIS), the Fagerström Test for Cigarette Dependence Questionnaire (FTCd), and the adult ADHD Self-Report Scale (ASRS-v1.1). RESULTS: Of the 506 patients, 51.0% of the participants demonstrated smartphone addiction. A significant association was also observed between extensive smartphone use and MDD (P = 0.001). Of the smokers in this study, 41.5% were addicted to smartphones (P = 0.039). Smartphone addicts had approximately two times the chance of having insomnia (OR = 2.113) (P = 0.013). In addition, they showcased more ADHD symptoms (OR = 2.712) (P < 0.001). CONCLUSIONS: We found a positive association among insomnia, depression, adult ADHD, and smartphone addiction, which confirms the findings reported in the previous studies. Therefore, we encourage the scientific community to further study the impacts of smartphone addiction on the mental health of postgraduate students.

Risks of adverse events in patients with orthostatic intolerance undergoing surgery with general anesthesia.

INTRODUCTION: Orthostatic intolerance (OI) is a group of disorders characterized by symptoms that occur upon standing and resolve with recumbence. Although well established but not widely recognized, these diagnoses may create uncertainty for clinicians dealing with a patient affected by OI and requiring a surgical procedure. OBJECTIVES: To determine the rate of intra- and postoperative major adverse events in patients with OI undergoing surgery with general anesthesia. METHODS: The study was a retrospective study of patients with orthostatic intolerance who underwent surgery requiring general anesthesia from 1 January 2000 to 31 December 2018. RESULTS: A total 171 patients with OI underwent 190 surgeries. In patients with POTS and orthostatic-induced VVS, there were no major significant adverse events. There was one episode of AVNRT in a patient with POTS and one episode of bradycardia secondary to vasovagal reflex in a patient with orthostatic-induced VVS. Moreover, there were 13 (6.8%) episodes of postoperative hypotension. However, the majority of these episodes were related to bleeding, volume depletion or sepsis. All cases of hypotension responded well to appropriate therapy. In patients with OH, the rate of postoperative major adverse cardiac events was 4.7%, and the 30-day mortality rate was 6.1%. This is not significantly different from the calculated risk for patients without OH. There were no myocardial infarctions or deaths at 30 days in patients with POTS or orthostatic-induced VVS. CONCLUSION: Patients with OI may not experience higher rates of perioperative complications compared with patients without OI syndromes.