Needle-perc-assisted endoscopic surgery versus retrograde intrarenal surgery for the treatment of 1- to 2-cm lower-pole renal stones in patients with unfavorable infundibulopelvic anatomy: a matched-pair analysis.

PURPOSE: To compare the safety and efficacy of needle-perc-assisted endoscopic surgery (NAES) and retrograde intrarenal surgery (RIRS) for the treatment of 1- to 2-cm lower-pole stones (LPS) in patients with complex infundibulopelvic anatomy. METHODS: Between June 2020 and July 2022, 32 patients with 1- to 2-cm LPS and unfavorable lower-pole anatomy for flexible ureteroscopy were treated with NAES. The outcomes of these patients were compared with patients who underwent RIRS using matched-pair analysis (1:1 scenario). The matching parameters such as age, gender, body mass index, stone size, hardness, and pelvicalyceal anatomy characteristics including infundibular pelvic angle, infundibular length, and width were recorded. Data were analyzed using the Student's t-test, Mann-Whitney U test, and Fisher's exact test. RESULTS: The two groups had similar baseline characteristics and lower-pole anatomy. The stone burden was comparable between both groups. NASE achieved a significantly better initial stone-free rate (SFR) than RIRS (87.5% vs 62.5%, p = 0.04). The auxiliary rates for the NAES and RIRS groups were 12.5% and 31.3%, respectively (p = 0.13). Finally, the SFR after 1 month follow-up period was still higher for the NAES group than RIRS group (93.8% versus 81.3%), but the difference was not statistically significant (p = 0.26). Concerning the operation duration, overall complication rates, and postoperative hospital stay, there were no differences between two groups. CONCLUSION: Compared to RIRS for treating 1- to 2-cm LPS in patients with unfavorable infundibulopelvic anatomy for flexible ureteroscopy, NAES was safe and effective with higher SFR and similar complication rate.

Endoscopic combined intrarenal surgery composed of micro-perc and retrograde intrarenal surgery in the treatment of complex kidney stones in children.

OBJECTIVE: This research aims to explore the efficiency and safety of endoscopic combined intrarenal surgery (Micro-ECIRS) composed of micro-percutaneous nephrolithotomy (Micro-perc) and retrograde intrarenal surgery (RIRS) in the Galdakao-modified supine Valdivia (GMSV) position for a single session for the treatment of complex nephrolithiasis in children. MATERIALS AND METHODS: This study retrospectively reviewed patients aged < 18 years who underwent Micro-ECIRS in the GMSV position for renal stones larger than 2 cm under ultrasound guidance between August 2020 to May 2022 at our institution. RESULTS: A total of 13 patients (8 males and 5 females) received Micro-ECIRS for renal stones under ultrasound guidancewhile adopting the GMSV position. The average stone size was 2.7 cm (range: 2.1-3.7 cm). Among them, 6 patients had left kidney stones, 5 patients had right kidney stones, and 2 patients had bilateral kidney stones. The mean operative time was 70.5 min (range: 54-93 min). The mean hospital stay was 6.4 days (range: 4-9 days). The mean hemoglobin decrease was 8.2 g/L (range: 5.1-12.4 g/L). The total number of kidneys that had complete stone clearance was 8 kidneys at 48 h postoperatively, 11 kidneys at 2 weeks postoperatively, and 14 kidneys at 1 month postoperatively. CONCLUSION: Our results demonstrate that Micro-ECIRS while patients are in the GMSV position is a safe and effective method for the treatment of complex children nephrolithiasis. However, all children made three hospital visits and received anesthesia three times. Further research is needed to confirm these findings.

Needle-perc-assisted endoscopic surgery (NAES) for patients with complicated solitary kidney stones: a prospective randomized study from a single center.

PURPOSE: The goal of this study is to compare traditional percutaneous nephrolithotomy (PCNL) and needle-perc-assisted endoscopic surgery (NAES) in the treatment of complicated solitary kidney stones via a single-center randomized controlled prospective study. METHODS: A total of patients with complex (Guy's score II-IV) solitary kidney stones between July 2019 to June 2022 were enrolled in the study. Participants were stratified into two groups: needle-perc-assisted endoscopic surgery group (group A) and traditional PCNL group (group B). All procedures were finished by X-ray free technique. The clinical characteristics and outcomes were analyzed. RESULTS: A total of 90 (44 in Group A and 46 in Group B) patients were finally included in our study. There were no statistically differences in terms of gender, age, body mass index (BMI), stone burden between two groups. The mean operative duration of Group A was significant higher than group B (95.1 ± 21.4 min vs 72.5 ± 29.5 min, p=0.02). The 1-month stone-free rate (SFR) was significant higher in Group A than B (90.9% vs 73.9%, p=0.03). A less hemoglobin drop (p=0.01), shorter postoperative in-hospital day (p=0.04), and lower severe complication (Clavien-Dindo III and above) rates (p=0.03) were observed in Group A. CONCLUSION: For patients with solitary kidney stones, NAES technique provides a higher one-session SFR, a better renal function recovery and compared with traditional PCNL.

Single-center experience of micro-perc in the treatment of children with 1.0-2.0 cm sized kidney stones in the Galdakao-modified supine Valdivia position.

OBJECTIVE: We aimed to explore the applicability and safety of micro-percutaneous nephrolithotomy (micro-perc) in the treatment of children with kidney stones in the Galdakao-modified supine Valdivia (GMSV) position under the guidance of whole-course ultrasound. MATERIALS AND METHODS: Patients were aged < 18 years in the GMSV position who underwent micro-perc for kidney stones under ultrasound guidance between August 2020 and May 2022 at our institution were reviewed retrospectively. RESULTS: A total of 23 patients, 15 males and 8 females, received micro-perc. The average stone size was 1.6 cm (range 1.1-2.0 cm). Among them, 12 patients had left kidney stones, 10 patients had right kidney stones, and 1 patient had bilateral kidney stones. The mean operative time was 55.3 min (range 35-86 min). The mean hospital stay was 2.9 days (range 2-4 days). The mean hemoglobin decrease was 1.7 g/L (range 0.9-3.2 g/L). A total of 17 patients had complete stone clearance at 48 h postoperatively. A total of 22 patients had complete stone clearance at 2 weeks postoperatively. CONCLUSION: Our results demonstrate that micro-perc under ultrasound guidance is a safe and effective method for the treatment of children with kidney stones in the GMSV position. Further research is warranted to confirm these results.

Clinical predictors of pulmonary embolism for inpatients: are computed tomography pulmonary angiograms being requested appropriately?

BACKGROUND: The heterogeneity of inpatient pulmonary embolism (PE) presentations may lead to computed tomography pulmonary angiograms (CTPA) being over-requested. Current clinical predictors for PE, including Wells criteria and Pulmonary Embolism Rule-out Criteria (PERC), have predominantly focussed on outpatient and emergency department populations. AIM: To determine the clinical indicators for ordering inpatient CTPA and the predictors of positive scans for PE. METHODS: Consecutive inpatient CTPA (performed >24 h after admission) from January 2017 to December 2017 were retrospectively reviewed. Variables including baseline characteristics, vital signs and risk factors for PE were extracted. RESULTS: A total of 312 CTPA was reviewed (average patient age 67 years; 46% male) and 36 CTPA were positive for PE (11.5%). The average time to inpatient CTPA request was 7 days. Clinical indicators associated with positive scans were hypoxia (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.1-5.6), tachypnoea (OR 2.5; 95% CI 1.2-6.0), recent surgery or immobilisation (OR 2.7; 95% CI 1.2-6.4), S1Q3T3 pattern on electrocardiogram (ECG; OR 7.2; 95% CI 1.4-35.7) and right bundle branch block pattern on ECG (OR 4.7; 95% CI 1.6-13.1). Hypotension, fever and malignancy were not significant. Both PERC and Wells criteria had poor positive predictive value (12% and 27% respectively), but the negative predictive value for PERC and Wells was 100% and 95.8% respectively. CONCLUSION: Inpatient CTPA appear to be over-requested and can potentially be rationalised based on a combination of clinical predictors and Wells criteria and/or PERC rule. Further prospective studies are needed to develop accurate clinical decision tools targeted towards inpatients.

Needle-Perc-Assisted Endoscopic Surgery in Treatment with Renal Staghorn Stones: A Prospective Randomized Controlled Study from a Large-Volume Stone Center.

INTRODUCTION: The goal of this study was to evaluate the efficacy and safety of needle-perc-assisted endoscopic surgery (NAES) in the treatment of staghorn renal stones via a single-center prospective randomized controlled study. METHODS: A total of 219 patients with partial or complete staghorn renal stones were prospectively randomized into two groups between January 2020 and April 2022. In group A (n = 112), patients were treated with traditional standard access, multiple if necessary, and in group B (n = 107), only one standard access was made, and needle-perc was assisted to remove the residual stones in the same stage. All procedures were guided under ultrasound totally. Stone size, operating time, blood loss, pain score, complications, and other related characteristics were monitored and analyzed. RESULTS: Procedures were successful in all patients. The baseline characters were similar between the groups. The mean stone size was comparable (4.5 ± 1.4 vs. 4.7 ± 1.7, p = 0.35). The 1-month stone-free status was achieved in 85 patients (75.9%) in group A and 80 (74.8%) patients in group B (p = 0.72). The operation time was shorter in group A than B (75.1 ± 28.1 min vs. 97.2 ± 20.4 min, p = 0.02). A less blood loss (p = 0.01), shorter hospital stay (p = 0.04), lower pain score (p = 0.04), and lower severe complication rates (p = 0.03) were observed in group B. CONCLUSION: NAES reveals better postoperative recurrence compared with traditional multiple tracts method for treating staghorn renal stones. The stone-free rate was comparable between the two groups.

Totally tubeless single access tract mini-percutaneous nephrolithotripsy in treatment of large burden > 2-cm and/or complex renal stones: a case series of 62 patients.

BACKGROUND: Limited literature has focused on the use of totally tubeless mini-percutaneous nephrolithotomy (PCNL) for the treatment of large renal stones. We present our findings of treating patients with large and/or complex renal stones using single renal access totally tubeless mini-PCNL. METHODS: From March 2018 to May 2021, 62 consecutive cases in which single tract totally tubeless mini-PCNL was used to treat complex renal stones were enrolled, all with calculi > 2 cm. All procedure of puncture and dilation were guided by fluoroscope. The complexity of stones was assessed according to the Guy's Scoring System (GSS). The surgical duration, length of hospital stay, analgesia requirement, stone-free rate, and perioperative morbidity were assessed. RESULTS: The mean preoperative stone burden was 36.69 ± 19.76 mm (above 2 cm in all cases), mean surgical duration was 61.93 ± 40.84 min (range 15-180 min), and mean hematocrit reduction was 4.67 ± 2.83%. Postoperative Nalbuphine was used in 6 patients. The mean length of stay was 2.46 ± 1.19 days (range 2-8 days), and the postoperative stone-free rate was 83.9% (52/62), and 87.1% (54/62) after auxiliary ESWL. The overall complication rate was 14.5%, the majority of complications being postoperative transient fever. CONCLUSION: For the treatment of large bursen > 2 cm and/or complex renal stones, totally tubeless single tract mini-PCNL ensures a feasible SFR, low morbidity and short hospital stay. According to the low complication rate in our study, the totally tubeless manner was not associated with an increased risk of postoperative morbidity, and patients benefited from decreased postoperative analgesics use.

Comparing 'clinical hunch' against clinical decision support systems (PERC rule, wells score, revised Geneva score and YEARS criteria) in the diagnosis of acute pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a common and potentially life-threatening condition. Since it is considered a 'do not miss' diagnosis, PE tends to be over-investigated beyond the evidence-based clinical decision support systems (CDSS), which in turn subjects patients to unnecessary radiation and contrast agent exposure with no apparent benefits in terms of outcome. The purpose of this study was to evaluate the yield of 'clinical hunch' (gestalt) and four CDSS: the PERC Rule, Wells score, revised Geneva score, and Years criteria. METHODS: A review was conducted on the Electronic Medical Records (EMR) of 1566 patients from the Emergency Department at a tertiary teaching hospital who underwent CTPA from the 1st of January 2018 to the 31st of December 2019. The scores for the four CDSS were calculated retrospectively from the EMR data. We considered that a CTPA had been ordered on a clinical hunch when there was no mention of CDSS in the EMR, and no D-dimer test. A bypass of CDSS was confirmed when any step of the diagnostic algorithms was not followed. RESULTS: Of the total 1566 patients who underwent CTPA, 265 (17%) were positive for PE. The diagnosis yield from the five decision groups (clinical hunch and four CDSS) was as follows-clinical hunch, 15%; PERC rule, 18% (6% when bypassed); Wells score, 19% (11% when bypassed); revised Geneva score, 26% (13% when bypassed); and YEARS criteria, 18% (6% when bypassed). CONCLUSION: Clinicians should trust the evidence-based clinical decision support systems in line with the international guidelines to diagnose PE.

An analysis of the "Half-Perc" versus open surgical placement method for a peritoneal dialysis catheter: a non-inferiority cohort study.

BACKGROUND: Most end-stage renal disease (ESRD) patients undergo open surgical techniques for peritoneal dialysis (PD) catheter placement. An alternative method to PD catheter implantation is the half-percutaneous ("Half-Perc") technique based on a modified trocar that is performed by a nephrologist. The single-center, retrospective, observational, cohort study presented here aimed to compare the effects of the "Half-Perc" technique with the traditional open surgery on peritoneal catheter insertion. METHODS: From January 2015 to January 2018, 240 ESRD patients who received initial PD catheter placement were divided into two groups based on the "Half-Perc" technique or open surgery. All patients were followed up for 365 days or until loss of initial PD catheter or death. Prism 5 software was used to analyze baseline characteristics, operation-related parameters, mechanical complications and clinical outcomes. RESULTS: The "Half-Perc" technique showed shorter operation time, shorter incision length, lower postoperative pain scores and quick initiation of the PD program compared to the open surgery. After the 365-day follow-up, the "Half-Perc" group showed a higher rate of catheter dysfunction (4% versus 0.9%) that was corrected by conservative treatment in most patients and a lower rate of peritonitis (4% versus 9.6%) but mechanical complications and clinical outcomes did not differ between the two groups. There was also no significant difference based on overall patient mortality or catheter removal. One-year initial catheter survival and true catheter survival were not statistically different between the groups. CONCLUSION: The "Half-Perc" placement of the PD catheter using a modified metal trocar appears to be a non-inferior alternative method and carries minimal invasiveness and risk compared to open surgical placement.

The impact of post PCNL tube type on blood loss and postoperative pain.

OBJECTIVE: To evaluate the impact of nephrostomy tube type on postoperative pain and blood loss following percutaneous nephrolithotomy (PCNL). METHODS: This is a prospective non-randomized study performed at Aga Khan University Hospital from July 2017 to June 2018. In this study we prospectively studied adult patients (16 to 65 years) who underwent unilateral PCNL. Patients who had nephrostomy with balloon (12Fr Foley's catheter) were compared with patients who had nephrostomy without balloon (12Fr Nelaton™ catheter). STONE Nephrolithometry score was used to assess the stone complexity. Mean pain score at six and 24 hours and mean hemoglobin drop at 24 hours was compared between two groups using independent sample t-test, p-value of <0.05 was considered significant. RESULTS: Over one year, 198 PCNL were performed out of which 119 were included for analysis. Sixty-six had nephrostomy tube with balloon and 53 had nephrostomy tube without balloon. Mean STONE score (9.66±1.4 vs. 9.64±1.24) and operative time (72.84±28.34 vs. 86.05±32.1 minutes) was comparable. Mean postoperative pain score at 6 hours and 24 hours postoperative was significantly lower in balloon group as compared to without balloon group. Mean Hemoglobin drop was similar in both groups (p=0.60). CONCLUSION: The use of nephrostomy tube with balloon after PCNL as this is associated with less pain and comparable hemoglobin drop as compare to nephrostomy tube without balloon.

New-onset seizure survey of epilepsy centers in the United States.

OBJECTIVES: Children presenting with new-onset seizures have variable access to resources and may not receive timely and adequate treatment. Some may experience adverse consequences when not evaluated in a timely manner by appropriate medical providers. Consequences can be especially severe for children under the age of two and for children who have psychiatric, cognitive, and behavioral comorbidities. There are no published data on how children with new-onset seizure are evaluated and treated across the US. Our goal was to gain insight into how different epilepsy centers across the country evaluate and treat children with new-onset seizures. METHODS: We conducted a survey of Epilepsy Centers in the US that are part of the Pediatric Epilepsy Research Consortium (PERC) and focused on children presenting with new-onset seizures; PERC is a group of pediatric epilepsy providers and researchers who participate in collaborative multicenter research in pediatric epilepsy with the goal of improving outcomes in children with pediatric epilepsy. The questionnaire was developed by the authors of this study. It was designed to provide a descriptive assessment of the consistency and variability in how patients with new-onset seizure are evaluated and treated at epilepsy sites across the country. The questionnaire was designed to assure all points of interest were explored. The questions were aimed at describing access to care, how care is delivered, whether centers prioritize based on clinical presentation and/or age, and availability of resources. The survey was sent to 80 epileptologists at 42 different Epilepsy Centers that are part of PERC. RESULTS: Respondents included 29 pediatric epileptologists representing 24 unique centers. In the cases where there were multiple respondents from each center, response of the most senior epileptologist was used. It is possible that the senior epileptologist may have not known about the center as much as a junior epileptologist, but this was used to establish consistencies among centers with multiple respondents. Results showed that 30% of centers had a dedicated new-onset seizure clinic. The median time for children to be seen was two to four weeks, and 12% reported that it takes more than five weeks until the patient is seen. There was a trend toward centers with new-onset seizure clinic having less wait times. Most centers identified lack of adequate care based on insurance coverage, resources, long wait times, and long travel times. SIGNIFICANCE: Most centers (70%) do not have a dedicated new-onset seizure clinic. Children presenting with new-onset seizures often do not receive timely and comprehensive care because of limitations in resources and lack of established standard of care. Standardizing care for patients presenting with new-onset seizures has not yet occurred in the US. Many centers do not have a screening process and employ staff other than physicians or nurses for screening and triaging patients. This study shows that having a neurologist or epileptologist in charge of triaging does not reduce wait times. This survey revealed that there is substantial variability in how these patients are evaluated. Although this study shows a trend for epilepsy centers with new-onset seizure clinic having less wait times, even when there is a new-onset seizure clinic, wait times can be greater than five weeks. Overall, however, a new-onset seizure clinic may be an effective way to improve access to timely and efficient care for these patients.

Use of a three-tiered clinical decision rule to quantify unnecessary radiological investigation of suspected pulmonary embolism.

BACKGROUND: Clinical decision rules for suspected pulmonary embolism are proposed to identify patients suitable for discharge without radiological investigation. Their use varies between institutions. AIMS: To quantify unnecessary radiological investigations for suspected pulmonary embolism (PE) as defined by a newly proposed three-tiered clinical decision rule incorporating the revised Geneva score, Pulmonary Embolism Rule-Out Criteria and D-dimer. To quantify missed diagnosis of PE if the proposed clinical decision rule were followed. METHODS: A retrospective audit was conducted; applying the proposed clinical decision rule to 584 emergency department (ED)-based encounters at the Royal Adelaide Hospital from May to November 2015. Encounters were confined to emergency presentations where suspected acute PE was investigated with computed tomography pulmonary angiography or ventilation-perfusion scanning; inpatient and follow-up studies were excluded. Sensitivity, specificity, positive predictive value and negative predictive value of the proposed clinical decision rule within the studied population were calculated. RESULTS: Data were obtained for 584 patient encounters where suspected PE was investigated radiologically. Applied retrospectively, the proposed clinical decision rule had a negative predictive value of 97.7% and a sensitivity of 98.5% for radiologically proven PE; 9.2% of scans could have been avoided. One case of PE would have been missed; a false-negative rate of 1.5%. CONCLUSION: Retrospective application of the proposed clinical decision rule to the studied cohort indicates at least 9% of radiological investigations were unnecessary. A prospective study is needed to assess the safety and cost-effectiveness of applying such a pathway to all patients presenting to ED with suspected PE.

A new minimally invasive technique for lead revision of perc-paddle leads.

To report on a less-invasive technique for replacing a broken lead in a spinal cord stimulation (SCS) device that makes use of St. Jude Medical's "Epiducer" device. A 53-year-old woman suffered a loss of stimulation on her internal pulse generator (IPG), which was found to have a broken lead. The broken lead was withdrawn using the Epiducer device with minimal invasiveness and without pain. A new lead was put in place, and successful stimulation using the IPG resumed. Follow-up 3 weeks later showed a well-functioning SCS system. An Epiducer can be used to revise the SCS system in a minimal invasive way without a new puncture. Follow-up study of this technique as well as others for revising an SCS system should be encouraged and used in comparison study.

Use of the d-dimer for Detecting Pulmonary Embolism in the Emergency Department.

BACKGROUND: Assessment for pulmonary embolism (PE) in the emergency department (ED) remains complex, involving clinical decision tools, blood tests, and imaging. OBJECTIVE: Our objective was to examine the test characteristics of the high-sensitivity d-dimer for the diagnosis of PE at our institution and evaluate use of the d-dimer and factors associated with a falsely elevated d-dimer. METHODS: We retrospectively collected data on adult patients evaluated with a d-dimer and computed tomography (CT) pulmonary angiogram or ventilation perfusion scan at two EDs between June 4, 2012 and March 30, 2016. We collected symptoms (dyspnea, unilateral leg swelling, hemoptysis), vital signs, and medical and social history (cancer, recent surgery, medications, history of deep vein thrombosis or PE, chronic obstructive pulmonary disease, smoking). We calculated test characteristics, including sensitivity, specificity, and likelihood ratios for the assay using conventional threshold and with age adjustment, and performed a univariate analysis. RESULTS: We found 3523 unique visits with d-dimer and imaging, detecting 198 PE. Imaging was pursued on 1270 patients with negative d-dimers, revealing 9 false negatives, and d-dimer was sent on 596 patients for whom negative Pulmonary Embolism Rule-Out Criteria (PERC) were documented with 2% subsequent radiographic detection of PE. The d-dimer showed a sensitivity of 95.7% (95% confidence interval [CI] 91-98%), specificity of 40.0% (95% CI 38-42%), negative likelihood ratio of 0.11 (95% CI 0.06-0.21), and positive likelihood ratio of 1.59 (95% CI 1.53-1.66) for the radiographic detection of PE. With age adjustment, 347 of the 2253 CT scans that were pursued in patients older than 50 years with an elevated d-dimer could have been avoided without missing any additional PE. Many risk factors, such as age, history of PE, recent surgery, shortness of breath, tachycardia and hypoxia, elevated the d-dimer, regardless of the presence of PE. CONCLUSIONS: Many patients with negative d-dimer and PERC still received imaging. Our data support the use of age adjustment, and perhaps adjustment for other factors seen in patients evaluated for PE.

Genetic analyses of Per.C6 cell clones producing a therapeutic monoclonal antibody regarding productivity and long-term stability.

Genetic characterization of protein-producing clones represents additional value to cell line development. In the present study, ten Per.C6 clones producing a Rebmab100 monoclonal antibody were selected using two cloning methods: six clones originated from limiting dilution cloning and four by the automated colony picker ClonePix FL. A stability program was performed for 50 generations, including 4 batches distributed along the timeframe to determine specific productivity (Qp) maintenance. Four stable clones (two from limiting dilution and two from ClonePix FL) were further evaluated. The relative mRNA expression levels of both heavy chain (HC) and light chain (LC) genes were verified at generations 0, 30-35, and 50-55 of the stability program. At generations 0 and 30-35, LC gene expression level was higher than HC gene, whereas at generation 50-55, the opposite prevailed. A high correlation was observed between Qp and HC or LC mRNA expression level for all clones at each generation analyzed along the continuous culture. The mRNA stability study was performed at steady-state culture. The LC gene displayed a higher half-life and lower decay constant than HC gene, accounting for the higher observed expression level of LC mRNA in comparison to HC mRNA. Clone R6 was highlighted due its high Qp, mRNA expression levels, and mRNA stability. Besides the benefits of applying genetic characterization for the selection of stable and high-producing clones, the present study shows for the first time the correlation between Qp and HC or LC expression levels and also mRNA stability in clones derived from human cell line Per.C6(®).

Advances in recombinant antibody manufacturing.

Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.

Characterization of apoptosis in PER.C6® batch and perfusion cultures.

Preventing or delaying cell death is a challenge in mammalian cell cultures for the development and optimization of production processes for biopharmaceuticals. Cell cultures need to be maintained highly viable for extended times in order to reach maximum production yields. Moreover, programmed cell death through apoptosis is often believed to occur without being detected by classical viability measurements. In this study, we characterized cell death in PER.C6® batch and perfusion cultures using three flow cytometry techniques measuring different steps of the apoptosis cascade: DNA fragmentation, caspases activation and phosphatidylserine externalization. We showed that apoptosis is the main pathway of PER.C6® cell death in batch cultures after depletion of main carbon sources. In high cell density perfusion cultures fed at a constant specific perfusion rate, both high viability and very limited apoptosis were observed. When extending this perfusion process far beyond standard operations, cultures were exposed to suboptimal process conditions, which resulted in an increase of apoptotic cell death. Moreover, we showed that the reference viability measurement using trypan blue exclusion properly assesses the level of cell death in PER.C6® cultures. This study is a first step in understanding the mechanisms of PER.C6® cell death, which will be helpful to support applications of the cell line.

Employing Si solar cell technology to increase efficiency of ultra-thin Cu(In,Ga)Se2 solar cells.

Reducing absorber layer thickness below 500 nm in regular Cu(In,Ga)Se2 (CIGS) solar cells decreases cell efficiency considerably, as both short-circuit current and open-circuit voltage are reduced because of incomplete absorption and high Mo/CIGS rear interface recombination. In this work, an innovative rear cell design is developed to avoid both effects: a highly reflective rear surface passivation layer with nano-sized local point contact openings is employed to enhance rear internal reflection and decrease the rear surface recombination velocity significantly, as compared with a standard Mo/CIGS rear interface. The formation of nano-sphere shaped precipitates in chemical bath deposition of CdS is used to generate nano-sized point contact openings. Evaporation of MgF2 coated with a thin atomic layer deposited Al2O3 layer, or direct current magnetron sputtering of Al2O3 are used as rear surface passivation layers. Rear internal reflection is enhanced substantially by the increased thickness of the passivation layer, and also the rear surface recombination velocity is reduced at the Al2O3/CIGS rear interface. (MgF2/)Al2O3 rear surface passivated ultra-thin CIGS solar cells are fabricated, showing an increase in short circuit current and open circuit voltage compared to unpassivated reference cells with equivalent CIGS thickness. Accordingly, average solar cell efficiencies of 13.5% are realized for 385 nm thick CIGS absorber layers, compared with 9.1% efficiency for the corresponding unpassivated reference cells.

Analysis of predictive factors in children with high suspicion of pulmonary embolism.

BACKGROUND AND AIM: Since there is a limited number of predictive models designed for pediatric patients with pulmonary embolism (PE), healthcare providers have resorted to utilizing the Wells criteria and PE Rule-out Criteria (PERC) that have been validated for use in adults. The objective of the study is to identify the predictive factors for PE and assess the effectiveness of the PERC, Wells, and pediatric-specific PE (PPE) criteria. METHODS: The study included individuals between the ages of 0-18 years who underwent pulmonary CT angiography and/or ventilation-perfusion scintigraphy with suspicion of PE. Demographic characteristics, symptoms, physical examination findings, risk factors, and laboratory and imaging results were retrospectively analyzed, and PERC, Wells, and PPE criteria were applied to the study population. RESULTS: Of the 110 patients included in the study, 27 (24.5%) had PE. Saturation, albumin, cough, calf swelling, central catheter, and malignancy were found to significantly contribute to the model. The total weighted risk score, which represents the sum of all predictive scores, ranged from 0 to 16 with a mean of 5.41 ± 4.02. When the cut-off >6.5, the model had good discrimination power for positive PE (AUC 0.79, 77% sensitivity, and 70% specificity). In our study, the Wells criteria showed a sensitivity of 96% and a specificity of 24%. The PERC exhibited a sensitivity of 96% and a specificity of 21%, while the PPE demonstrated a sensitivity of 74% and a specificity of 30%. CONCLUSION: While the sensitivity of Wells, PERC, and PPE models was higher than our developed model, their specificities were considerably lower than our model.

Testosterone Therapy as an Isolated Risk Factor for Venous Thrombosis: A Case Report.

Healthcare providers in the emergency department (ED) diagnose and treat venous thrombus embolism (VTE). Current VTE clinical decision tools specifically mention estrogen but do not include the use of testosterone replacement therapy (TRT). A male in the early third decade of life presented to the ED with complaints of left calf pain and subjective swelling for one week. The patient was low risk using VTE scoring tools. The patient had multiple occlusive VTE on lower-extremity ultrasound and extensive central, bilateral segmental, and subsegmental pulmonary emboli. He was admitted to the hospital and placed on a heparin drip. TRT may be seen in clinical practice in both male and female patients. This bodes the question of whether TRT should be added to the risk analysis tools used to evaluate and predict the risk for VTE. There have been conflicting reports in research, with more recent studies indicating the risk associated with TRT. This case study demonstrates the risk of VTE with TRT. Further investigation is needed to determine if there is a correlation between VTE and TRT. Clinical decision tools should be updated to include TRT accordingly.