Michael Boettcher | University of Mannheim (original) (raw)

articles by Michael Boettcher

Urology, 2012

To distinguish the prognostic factors that decrease the probability of a negative exploration for... more To distinguish the prognostic factors that decrease the probability of a negative exploration for "acute scrotum." In some institutes, patients with "acute scrotum" undergo immediate exploration after clinical evaluation. Because testicular torsion (TT) accounts only for a fraction of these cases, most infants can be treated conservatively.

BJU International, 2013

• To test the clinical and sonographic predictors of testicular torsion (TT) with the aim of redu... more • To test the clinical and sonographic predictors of testicular torsion (TT) with the aim of reducing negative exploration rates.

Diabetologia, 2008

Aims/hypothesis Different ectopic fat depots, such as visceral or hepatic fat, are known to affec... more Aims/hypothesis Different ectopic fat depots, such as visceral or hepatic fat, are known to affect whole body insulin sensitivity. It has recently been hypothesised that differences in perivascular adipose tissue (PVAT) mass around resistance vessels may also contribute to insulin resistance, possibly via direct vascular effects leading to reduced capillary cross-sectional area in the muscle, which in turn affects muscular blood flow and glucose uptake. Based on this, the aim of the present study was to test whether PVAT around conduit arteries (i.e. the brachial artery) influences NO bioavailability, expressed as flowmediated dilation (FMD), or insulin sensitivity in humans in vivo. Methods Insulin sensitivity was measured by OGTT in all 95 participants (59 women, 36 men; median age 47 years, range 19-66 years) and by the gold standard, a euglycaemic-hyperinsulinaemic clamp, in a randomly selected subgroup of 33 participants. Quantification of the different fat compartments, including PVAT around the brachial artery, was achieved by high-resolution magnetic resonance imaging (1.5 T). Blood flow and FMD were measured at the brachial artery using high-resolution (13 MHz) ultrasound, after 5 min of forearm occlusion. Results PVAT was negatively correlated with insulin sensitivity and the post-ischaemic increase in blood flow. The association between PVAT and insulin sensitivity (r= −0.54, β=−0.37, p=0.009) was independent of age, sex, visceral adipose tissue, liver fat, BMI and further cardiovascular risk factors. No correlation could be detected between PVAT and local endothelial function. However, we observed an independent association between PVAT and post-ischaemic increase in blood flow (r=−0.241; β=−1.69; p=0.02). Conclusions/interpretation PVAT seems to play an independent role in the pathogenesis of insulin resistance. This may be due to direct vascular effects influencing muscular blood flow.

European Journal of Pediatric Surgery, 2014

Background Prospective data of transumbilically laparoscopic-assisted appendectomies (TULAA) is a... more Background Prospective data of transumbilically laparoscopic-assisted appendectomies (TULAA) is absent in the pediatric population. We therefore compared the midterm outcome of TULAA with open (OA) and laparoscopic (LA) appendectomies in children with appendicitis in a matched prospective study. Methods A total of 20 patients operated with TULAA were matched to 20 cases operated by LA and OA, respectively, according to sex, age, and histology of the resected appendix. All 60 children were evaluated during a 3-month follow-up visit. Results The subjective pain level after discharge, the rate of complications, and persistent painful wound as well as the duration of days refraining from school or kindergarten were similar in all three groups. The wound satisfaction was significantly higher in TULAA and LA. Children operated with TULAA had a faster return to full physical activity compared with OA. Conclusion Our data suggest that TULAA, LA, and OA have a similar outcome 3 months after surgery apart from cosmetic appearance of the wound and return to full physical activity in pediatric patients. Whether parental bias or the increased wound satisfaction act as confounders for early return to full physical activity should be evaluated in larger prospective randomized trials.

Fetal Diagnosis and Therapy, 2013

The embryogenesis of gastroschisis is not completely understood. The aim of our study was to eval... more The embryogenesis of gastroschisis is not completely understood. The aim of our study was to evaluate the impact of a simple abdominal wall defect versus a defect including eviscerated intestine or omentum for the development of gastroschisis in a fetal lamb model. At mid-gestation (day 77) an abdominal wall defect was fetoscopically created with three different approaches in 19 German blackhead sheep. The intestine was eviscerated in 7 fetuses (group 1). The peritoneum was incised and a patch of the omentum pulled through the incision in 5 fetuses (group 2). In 7 fetuses (group 3) the skin and rectus muscle were incised until the peritoneum was visible. In this group, no abdominal contents were exteriorized and the peritoneum was left intact. A second fetoscopic procedure was performed 21 days later, assessing the condition and extension of eviscerated bowel. The fetus was retrieved by Cesarean section on day 132 and evaluated. The second fetoscopy acting as a control for the creation of gastroschisis demonstrated eviscerated and inflamed intestine in all 3 groups. The amount of eviscerated intestine did not appear to depend on the size of the defect nor on its duration. It appears that a simple incision of the abdominal wall with intact peritoneum is sufficient for the development of gastroschisis in a fetal sheep model. This finding may improve the understanding of the etiology of gastroschisis.

Journal of Magnetic Resonance Imaging, 2009

Purpose: To quantify intermuscular adipose tissue (IMAT) of the lower leg as well as to investiga... more Purpose: To quantify intermuscular adipose tissue (IMAT) of the lower leg as well as to investigate associations with other adipose tissue (AT) compartments. The relationship between IMAT and insulin sensitivity was also examined.

Malaria Journal, 2011

Background: Rapid and accurate diagnosis of malaria is central to clinical management and the pre... more Background: Rapid and accurate diagnosis of malaria is central to clinical management and the prevention of drug-overuse, which may lead to resistance development, toxicity and economic losses. So far, light microscopy (LM) of Giemsa-stained thick blood smears is the gold standard. Under optimal conditions the procedure is fast and reliable; nevertheless a gain in speed would be a great advantage. Rapid diagnosis tests are an alternative, although they cost more and give qualitative instead of quantitative results. Light-emitting diode (LED) fluorescence microscopy (ledFM 400 ×, 1000 ×) may offer a reliable and cheap alternative, which can be used at the point of care.

Microsurgery, 2009

In this report, we describe the first case of using the partial phrenic nerve transfer and direct... more In this report, we describe the first case of using the partial phrenic nerve transfer and direct muscular implantation into the deltoid muscle for restoration of the shoulder function and stability. A patient suffering from the partial brachial plexus injury with absent axillary nerve underwent reconstructive surgery by an end-to-end nerve coaptation using two fascicles of the phrenic nerve and two autologous nerve grafts, and direct implantation of nerve grafts into the deltoid muscle. Eighteen months after the procedure, we found a functioning biceps with 90 degrees elbow flexion against gravity and 40 degrees shoulder abduction with satisfactory shoulder stability. Electrophysiology revealed reinnervation potentials in the deltoid and biceps muscle. This case demonstrates a satisfactory result after using transfer of the partial ipsilateral phrenic nerve in combination with muscular implantation to restore shoulder abduction and stability. We recommend the described techniques in cases without other reconstructive options. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

Pediatric Surgery International, 2014

Prognosis of midgut volvulus in neonates and infants younger than 1 year remains poor, as diagnos... more Prognosis of midgut volvulus in neonates and infants younger than 1 year remains poor, as diagnostic findings may not be apparent until gut infarction had occurred. To characterize factors that help to predict complex midgut volvulus early was aim of this study. Institutionally approved retrospective analysis of all children younger than 1 year treated for midgut volvulus at the author's center from January 2002 to December 2011. Medical history, symptoms, laboratory and radiologic findings as well as sequelae of midgut volvulus were evaluated. In 10 years, 37 children fulfilled the inclusion criteria. Of these, 43% developed complications, and mortality rate was 16%. In 30% of the patients, the only clinical sign was a sudden worsening of the general condition and abdominal distension (complex 19% vs. simple 38%). In one child with simple midgut volvulus, all clinical, laboratory and radiologic signs were negative. CART analysis identified a base excess below -1.70 and preterm birth (<36 weeks) as the best discriminators of complex and simple midgut volvulus. A score >1pt (comprised of these two factors) was found in all children with complex and in 14% of simple midgut volvulus (p < 0.001). A positive score (>1pt) offers a sensitivity of 100% (81.7-100%), specificity of 85.7% (71.8-85.7%), a PPV of 84.2% (68.8-84.2%) and NPV 100% (83.8-100%). The study shows that midgut volvulus has a substantial morbidity and mortality. Unfortunately, not all affected children get picked up by history, laboratory and imaging. However, the proposed score helps to identify subject with increased risk of complications. It has the potential to facilitate and accelerate diagnosis of complex midgut volvulus; ultimately, it might help to reduce morbidity and mortality.

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2007

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2007

Surgical Endoscopy, 2014

The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel fo... more The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel formation and disorganization of interstitial Cajal cells (ICC) have been proposed in humans. The aim of this study was to evaluate the impact of prenatal coverage of gastroschisis on gut inflammation and expression of ICC in a fetal lamb model. Twenty-one German blackhead sheep with an abdominal wall defect that was created fetoscopically on day 77 of 145 days gestation were used in this study. Intrauterine surgery with the aim to cover the defect was performed 3 weeks later; two fetuses were covered completely, 5 partially and 11 remained uncovered. Three fetuses without gastroschisis were used as controls. All fetuses were retrieved by cesarean section at day 135. Samples of the small intestine were stained with hematoxylin and eosin for histologic analysis of peel formation and serosal and muscular thickness. For ICC detection, immunohistochemistry using anti-CD117 (c-Kit) antibody was used. In all samples with exposure to amniotic fluid, peel formation and significantly decreased ICC were found. Complete coverage reduced peel formation and disorganization of ICC compared to uncovered animals almost to the level of controls. Peel formation and ICC derangement were significantly reduced by prenatal coverage of gastroschisis. Moreover, this animal model mimics the histopathological bowel changes as seen in human gastroschisis and may, therefore, be used for further research on the pathophysiology and fetal therapy of this malformation.

Urology, 2013

To identify the signs that can help to differentiate torsion of the appendix testis (AT) and epid... more To identify the signs that can help to differentiate torsion of the appendix testis (AT) and epididymitis and to establish the incidence of the various pathologic entities in boys with an acute scrotum. A retrospective study was performed of the data from all boys treated at our institute from January 2008 to January 2012 for the diagnosis of an "acute scrotum." The clinical and, if available, ultrasound findings were documented. Differences between groups were calculated using a chi-square test or analysis of variance and classification and regression tree analysis. A total of 241 boys with acute scrotal pain were included and underwent surgical exploration. Of the 241 boys, 163 (70%) had AT, 44 (18.5%) had epididymitis, 31 (13.3%) had testicular torsion, and 3 (1.3%) had idiopathic scrotal edema. The incidence of AT was significantly increased in the colder months (P = .01). We found that AT and epididymitis shared several aspects but differed regarding dysuria (epididymitis, P ≤.001), a painful epididymis on palpation (epididymitis, P = .028), increased epididymal echogenicity (epididymitis, P = .043), augmented peritesticular perfusion (epididymitis, P = .05), and a positive blue dot sign (AT, P <.001). The classification and regression tree analysis showed that the presence of dysuria, a positive blue dot sign, and a painful epididymis are the best factors for distinguishing AT and epididymitis. Most children with an acute scrotum will have AT or epididymitis. It will be possible to differentiate most cases using the clinical and ultrasound findings. In our study, the best predictors were dysuria, a painful epididymis on palpation, and altered epididymal echogenicity and increased peritesticular perfusion found on ultrasound studies for epididymitis and a positive blue dot sign for AT.

Monatsschrift Kinderheilkunde, 2012

ABSTRACT Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend beh... more ABSTRACT Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend behandelt. Bisher gab es keine Informationen zum Schmerzmanagement von Kinderkrankenhäusern in der Schweiz. Ziel der vorliegenden Studie war, den aktuellen Stand der Schmerzerfassung, -interpretation und -behandlung zu bestimmen. Studiendesign Ein Fragebogen wurde an alle pädiatrischen Krankenhäuser in der Schweiz gesendet. Ergebnisse Insgesamt antworteten 27 von 45 Einheiten (Antwortrate: 60%). Die meisten Abteilungen verwenden Schmerzerfassungstools (96%) und führten diesbezügliche Leitlinien ein (78%). Die Behandlung von Schmerzen erfolgt ebenfalls meist nach hausinterner Leitlinie (78%). Prozedurale und postoperative Schmerzen werden stets (100%) analgetisch behandelt. Bei Frühgeborenen und Kindern auf Intensivpflegestationen werden bei invasiven Eingriffen häufig Analgetika (> 87%) verwendet. Auf Intensivstationen liegen in 44% diesbezügliche Leitlinien vor. Resümee Der Nutzen eines effektiven Schmerzmanagements bei Kindern ist eindeutig belegt. Viele Ansätze zur Verbesserung werden in der Schweiz gut umgesetzt. Vor allem im internationalen Vergleich verbesserte sich das Schmerzmanagement. Es gibt aber noch Optimierungsmöglichkeiten. Beispielsweise besitzen weniger als die Hälfte aller schweizerischen Intensivstationen eine Leitlinie für die Behandlung von Schmerzen bei invasiven Eingriffen.

Besides the pure adipose tissue, as subcutaneous adipose tissue or visceral adipose tissue, the s... more Besides the pure adipose tissue, as subcutaneous adipose tissue or visceral adipose tissue, the so-called ectopic fat in organs which do normally contain no fat at all but are affected by insulin resistance, as intramyocellular lipids (IMCL) in skeletal muscle or hepatic lipids (IHL) in the liver, play an important role in the pathogenesis of insulin resistance and type 2 diabetes [1,2]. IMCL can reliably be determined by 1 H MRS and show a negative correlation to insulin sensitivity [1]. Probably, besides IMCL, also the amount of fatty septa nestled along the muscle fiber bundles might be of importance. As single voxel 1 H MRS does not allow a quantification of this intermuscular fat (IMF) depot, the aim of this study was to quantify IMF by T1weighted MRI and to compare the results with anthropometric and metabolic data in a cohort at increased risk for type 2 diabetes mellitus (T2DM).

Schmerzen zählen zu den belastendsten Stimuli, denen ein Kind während eines Krankenhausaufenthalt... more Schmerzen zählen zu den belastendsten Stimuli, denen ein Kind während eines Krankenhausaufenthalts ausgesetzt sein kann. Bis vor einiger Zeit wurden sie als unabdingbarer Teil der Behandlung angesehen und sogar häufig ignoriert. 1968 stellte Swaford fest, dass lediglich 2 von 60 pädiatrischen Patienten nach einem viszeralen Eingriff Schmerzmittel benötigten, und schloss daraus, "pediatric patients seldom need medication for the relief of pain. They tolerate discomfort well. The child will say he does not feel well or that he is uncomfortable, that he wants his parents but often he will not relate this unhappiness to pain." Damals galten Neugeborene zudem als schmerzunempfindlich .

Eplasty, 2010

This report describes a case where 4 digits were replanted in a mentally retarded patient with a ... more This report describes a case where 4 digits were replanted in a mentally retarded patient with a history of smoking and the inability to follow postoperative arrangements.

Journal of pediatric surgery, 2014

Comparison of the outcome of newborns with simple (sGS) and complex gastroschisis (cGS: gastrosch... more Comparison of the outcome of newborns with simple (sGS) and complex gastroschisis (cGS: gastroschisis with atresia, necrosis, perforation or volvulus). We conducted a systematic database search, quality assessment and meta-analyzed relevant articles which evaluated the mortality and morbidity of newborns with cGS versus sGS. Risk ratios (RR) with 95% confidence interval (CI) were reported for categorical data, and the mean difference (MD) was calculated for continuous data. Pooled estimates of RR and MD were computed using generic inverse variance and a random-effects model. Of 19 identified reports, 13 eligible studies were included. The mortality of infants with cGS (16.67%) was significantly higher than sGS (2.18%, RR: 5.39 [2.42, 12.01], p<0.0001). Significantly different outcome was found for the following parameters: Infants with cGS are started on enteral feedings later and they take longer to full enteral feedings with a subsequent longer duration of parenteral nutrition....

European Journal of Pediatric Surgery, 2015

Background Implementation of complex fetoscopic procedures that included intracorporeal suturing ... more Background Implementation of complex fetoscopic procedures that included intracorporeal suturing has been limited due to technical difficulties that might be surmounted with adequate training. Evaluating the impact of laparoscopic or fetoscopic training on fetoscopic performance was the aim of this study. Methods To evaluate fetoscopic performance after either laparoscopic or fetoscopic training, subjects were asked to perform four surgeon&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s square knots fetoscopically prior and post 2 hours of hands-on training. All subjects were medical students and novice in laparoscopic and fetoscopic interventions. Total time, knot stability (evaluated via tensiometer), suture accuracy, knot quality, and fetoscopic performance were assessed. Results Forty-six subjects were included in the study; after simple randomization, 24 were trained fetoscopically and 22 laparoscopically. Both groups had comparable baseline characteristics and improved after training significantly regarding all aspects assessed in this study. Subjects who trained fetoscopically were superior in terms of suturing and knot-tying performance. Conclusion Training significantly improves fetoscopic performance and may indeed be the keystone for future complex fetoscopic interventions. It seems advisable to train rather fetoscopically than laparoscopically resulting in higher suture and knot-tying quality.

Urology, 2012

To distinguish the prognostic factors that decrease the probability of a negative exploration for... more To distinguish the prognostic factors that decrease the probability of a negative exploration for "acute scrotum." In some institutes, patients with "acute scrotum" undergo immediate exploration after clinical evaluation. Because testicular torsion (TT) accounts only for a fraction of these cases, most infants can be treated conservatively.

BJU International, 2013

• To test the clinical and sonographic predictors of testicular torsion (TT) with the aim of redu... more • To test the clinical and sonographic predictors of testicular torsion (TT) with the aim of reducing negative exploration rates.

Diabetologia, 2008

Aims/hypothesis Different ectopic fat depots, such as visceral or hepatic fat, are known to affec... more Aims/hypothesis Different ectopic fat depots, such as visceral or hepatic fat, are known to affect whole body insulin sensitivity. It has recently been hypothesised that differences in perivascular adipose tissue (PVAT) mass around resistance vessels may also contribute to insulin resistance, possibly via direct vascular effects leading to reduced capillary cross-sectional area in the muscle, which in turn affects muscular blood flow and glucose uptake. Based on this, the aim of the present study was to test whether PVAT around conduit arteries (i.e. the brachial artery) influences NO bioavailability, expressed as flowmediated dilation (FMD), or insulin sensitivity in humans in vivo. Methods Insulin sensitivity was measured by OGTT in all 95 participants (59 women, 36 men; median age 47 years, range 19-66 years) and by the gold standard, a euglycaemic-hyperinsulinaemic clamp, in a randomly selected subgroup of 33 participants. Quantification of the different fat compartments, including PVAT around the brachial artery, was achieved by high-resolution magnetic resonance imaging (1.5 T). Blood flow and FMD were measured at the brachial artery using high-resolution (13 MHz) ultrasound, after 5 min of forearm occlusion. Results PVAT was negatively correlated with insulin sensitivity and the post-ischaemic increase in blood flow. The association between PVAT and insulin sensitivity (r= −0.54, β=−0.37, p=0.009) was independent of age, sex, visceral adipose tissue, liver fat, BMI and further cardiovascular risk factors. No correlation could be detected between PVAT and local endothelial function. However, we observed an independent association between PVAT and post-ischaemic increase in blood flow (r=−0.241; β=−1.69; p=0.02). Conclusions/interpretation PVAT seems to play an independent role in the pathogenesis of insulin resistance. This may be due to direct vascular effects influencing muscular blood flow.

European Journal of Pediatric Surgery, 2014

Background Prospective data of transumbilically laparoscopic-assisted appendectomies (TULAA) is a... more Background Prospective data of transumbilically laparoscopic-assisted appendectomies (TULAA) is absent in the pediatric population. We therefore compared the midterm outcome of TULAA with open (OA) and laparoscopic (LA) appendectomies in children with appendicitis in a matched prospective study. Methods A total of 20 patients operated with TULAA were matched to 20 cases operated by LA and OA, respectively, according to sex, age, and histology of the resected appendix. All 60 children were evaluated during a 3-month follow-up visit. Results The subjective pain level after discharge, the rate of complications, and persistent painful wound as well as the duration of days refraining from school or kindergarten were similar in all three groups. The wound satisfaction was significantly higher in TULAA and LA. Children operated with TULAA had a faster return to full physical activity compared with OA. Conclusion Our data suggest that TULAA, LA, and OA have a similar outcome 3 months after surgery apart from cosmetic appearance of the wound and return to full physical activity in pediatric patients. Whether parental bias or the increased wound satisfaction act as confounders for early return to full physical activity should be evaluated in larger prospective randomized trials.

Fetal Diagnosis and Therapy, 2013

The embryogenesis of gastroschisis is not completely understood. The aim of our study was to eval... more The embryogenesis of gastroschisis is not completely understood. The aim of our study was to evaluate the impact of a simple abdominal wall defect versus a defect including eviscerated intestine or omentum for the development of gastroschisis in a fetal lamb model. At mid-gestation (day 77) an abdominal wall defect was fetoscopically created with three different approaches in 19 German blackhead sheep. The intestine was eviscerated in 7 fetuses (group 1). The peritoneum was incised and a patch of the omentum pulled through the incision in 5 fetuses (group 2). In 7 fetuses (group 3) the skin and rectus muscle were incised until the peritoneum was visible. In this group, no abdominal contents were exteriorized and the peritoneum was left intact. A second fetoscopic procedure was performed 21 days later, assessing the condition and extension of eviscerated bowel. The fetus was retrieved by Cesarean section on day 132 and evaluated. The second fetoscopy acting as a control for the creation of gastroschisis demonstrated eviscerated and inflamed intestine in all 3 groups. The amount of eviscerated intestine did not appear to depend on the size of the defect nor on its duration. It appears that a simple incision of the abdominal wall with intact peritoneum is sufficient for the development of gastroschisis in a fetal sheep model. This finding may improve the understanding of the etiology of gastroschisis.

Journal of Magnetic Resonance Imaging, 2009

Purpose: To quantify intermuscular adipose tissue (IMAT) of the lower leg as well as to investiga... more Purpose: To quantify intermuscular adipose tissue (IMAT) of the lower leg as well as to investigate associations with other adipose tissue (AT) compartments. The relationship between IMAT and insulin sensitivity was also examined.

Malaria Journal, 2011

Background: Rapid and accurate diagnosis of malaria is central to clinical management and the pre... more Background: Rapid and accurate diagnosis of malaria is central to clinical management and the prevention of drug-overuse, which may lead to resistance development, toxicity and economic losses. So far, light microscopy (LM) of Giemsa-stained thick blood smears is the gold standard. Under optimal conditions the procedure is fast and reliable; nevertheless a gain in speed would be a great advantage. Rapid diagnosis tests are an alternative, although they cost more and give qualitative instead of quantitative results. Light-emitting diode (LED) fluorescence microscopy (ledFM 400 ×, 1000 ×) may offer a reliable and cheap alternative, which can be used at the point of care.

Microsurgery, 2009

In this report, we describe the first case of using the partial phrenic nerve transfer and direct... more In this report, we describe the first case of using the partial phrenic nerve transfer and direct muscular implantation into the deltoid muscle for restoration of the shoulder function and stability. A patient suffering from the partial brachial plexus injury with absent axillary nerve underwent reconstructive surgery by an end-to-end nerve coaptation using two fascicles of the phrenic nerve and two autologous nerve grafts, and direct implantation of nerve grafts into the deltoid muscle. Eighteen months after the procedure, we found a functioning biceps with 90 degrees elbow flexion against gravity and 40 degrees shoulder abduction with satisfactory shoulder stability. Electrophysiology revealed reinnervation potentials in the deltoid and biceps muscle. This case demonstrates a satisfactory result after using transfer of the partial ipsilateral phrenic nerve in combination with muscular implantation to restore shoulder abduction and stability. We recommend the described techniques in cases without other reconstructive options. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

Pediatric Surgery International, 2014

Prognosis of midgut volvulus in neonates and infants younger than 1 year remains poor, as diagnos... more Prognosis of midgut volvulus in neonates and infants younger than 1 year remains poor, as diagnostic findings may not be apparent until gut infarction had occurred. To characterize factors that help to predict complex midgut volvulus early was aim of this study. Institutionally approved retrospective analysis of all children younger than 1 year treated for midgut volvulus at the author&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s center from January 2002 to December 2011. Medical history, symptoms, laboratory and radiologic findings as well as sequelae of midgut volvulus were evaluated. In 10 years, 37 children fulfilled the inclusion criteria. Of these, 43% developed complications, and mortality rate was 16%. In 30% of the patients, the only clinical sign was a sudden worsening of the general condition and abdominal distension (complex 19% vs. simple 38%). In one child with simple midgut volvulus, all clinical, laboratory and radiologic signs were negative. CART analysis identified a base excess below -1.70 and preterm birth (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;36 weeks) as the best discriminators of complex and simple midgut volvulus. A score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1pt (comprised of these two factors) was found in all children with complex and in 14% of simple midgut volvulus (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). A positive score (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1pt) offers a sensitivity of 100% (81.7-100%), specificity of 85.7% (71.8-85.7%), a PPV of 84.2% (68.8-84.2%) and NPV 100% (83.8-100%). The study shows that midgut volvulus has a substantial morbidity and mortality. Unfortunately, not all affected children get picked up by history, laboratory and imaging. However, the proposed score helps to identify subject with increased risk of complications. It has the potential to facilitate and accelerate diagnosis of complex midgut volvulus; ultimately, it might help to reduce morbidity and mortality.

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2007

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2007

Surgical Endoscopy, 2014

The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel fo... more The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel formation and disorganization of interstitial Cajal cells (ICC) have been proposed in humans. The aim of this study was to evaluate the impact of prenatal coverage of gastroschisis on gut inflammation and expression of ICC in a fetal lamb model. Twenty-one German blackhead sheep with an abdominal wall defect that was created fetoscopically on day 77 of 145 days gestation were used in this study. Intrauterine surgery with the aim to cover the defect was performed 3 weeks later; two fetuses were covered completely, 5 partially and 11 remained uncovered. Three fetuses without gastroschisis were used as controls. All fetuses were retrieved by cesarean section at day 135. Samples of the small intestine were stained with hematoxylin and eosin for histologic analysis of peel formation and serosal and muscular thickness. For ICC detection, immunohistochemistry using anti-CD117 (c-Kit) antibody was used. In all samples with exposure to amniotic fluid, peel formation and significantly decreased ICC were found. Complete coverage reduced peel formation and disorganization of ICC compared to uncovered animals almost to the level of controls. Peel formation and ICC derangement were significantly reduced by prenatal coverage of gastroschisis. Moreover, this animal model mimics the histopathological bowel changes as seen in human gastroschisis and may, therefore, be used for further research on the pathophysiology and fetal therapy of this malformation.

Urology, 2013

To identify the signs that can help to differentiate torsion of the appendix testis (AT) and epid... more To identify the signs that can help to differentiate torsion of the appendix testis (AT) and epididymitis and to establish the incidence of the various pathologic entities in boys with an acute scrotum. A retrospective study was performed of the data from all boys treated at our institute from January 2008 to January 2012 for the diagnosis of an &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;acute scrotum.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; The clinical and, if available, ultrasound findings were documented. Differences between groups were calculated using a chi-square test or analysis of variance and classification and regression tree analysis. A total of 241 boys with acute scrotal pain were included and underwent surgical exploration. Of the 241 boys, 163 (70%) had AT, 44 (18.5%) had epididymitis, 31 (13.3%) had testicular torsion, and 3 (1.3%) had idiopathic scrotal edema. The incidence of AT was significantly increased in the colder months (P = .01). We found that AT and epididymitis shared several aspects but differed regarding dysuria (epididymitis, P ≤.001), a painful epididymis on palpation (epididymitis, P = .028), increased epididymal echogenicity (epididymitis, P = .043), augmented peritesticular perfusion (epididymitis, P = .05), and a positive blue dot sign (AT, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.001). The classification and regression tree analysis showed that the presence of dysuria, a positive blue dot sign, and a painful epididymis are the best factors for distinguishing AT and epididymitis. Most children with an acute scrotum will have AT or epididymitis. It will be possible to differentiate most cases using the clinical and ultrasound findings. In our study, the best predictors were dysuria, a painful epididymis on palpation, and altered epididymal echogenicity and increased peritesticular perfusion found on ultrasound studies for epididymitis and a positive blue dot sign for AT.

Monatsschrift Kinderheilkunde, 2012

ABSTRACT Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend beh... more ABSTRACT Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend behandelt. Bisher gab es keine Informationen zum Schmerzmanagement von Kinderkrankenhäusern in der Schweiz. Ziel der vorliegenden Studie war, den aktuellen Stand der Schmerzerfassung, -interpretation und -behandlung zu bestimmen. Studiendesign Ein Fragebogen wurde an alle pädiatrischen Krankenhäuser in der Schweiz gesendet. Ergebnisse Insgesamt antworteten 27 von 45 Einheiten (Antwortrate: 60%). Die meisten Abteilungen verwenden Schmerzerfassungstools (96%) und führten diesbezügliche Leitlinien ein (78%). Die Behandlung von Schmerzen erfolgt ebenfalls meist nach hausinterner Leitlinie (78%). Prozedurale und postoperative Schmerzen werden stets (100%) analgetisch behandelt. Bei Frühgeborenen und Kindern auf Intensivpflegestationen werden bei invasiven Eingriffen häufig Analgetika (&gt; 87%) verwendet. Auf Intensivstationen liegen in 44% diesbezügliche Leitlinien vor. Resümee Der Nutzen eines effektiven Schmerzmanagements bei Kindern ist eindeutig belegt. Viele Ansätze zur Verbesserung werden in der Schweiz gut umgesetzt. Vor allem im internationalen Vergleich verbesserte sich das Schmerzmanagement. Es gibt aber noch Optimierungsmöglichkeiten. Beispielsweise besitzen weniger als die Hälfte aller schweizerischen Intensivstationen eine Leitlinie für die Behandlung von Schmerzen bei invasiven Eingriffen.

Besides the pure adipose tissue, as subcutaneous adipose tissue or visceral adipose tissue, the s... more Besides the pure adipose tissue, as subcutaneous adipose tissue or visceral adipose tissue, the so-called ectopic fat in organs which do normally contain no fat at all but are affected by insulin resistance, as intramyocellular lipids (IMCL) in skeletal muscle or hepatic lipids (IHL) in the liver, play an important role in the pathogenesis of insulin resistance and type 2 diabetes [1,2]. IMCL can reliably be determined by 1 H MRS and show a negative correlation to insulin sensitivity [1]. Probably, besides IMCL, also the amount of fatty septa nestled along the muscle fiber bundles might be of importance. As single voxel 1 H MRS does not allow a quantification of this intermuscular fat (IMF) depot, the aim of this study was to quantify IMF by T1weighted MRI and to compare the results with anthropometric and metabolic data in a cohort at increased risk for type 2 diabetes mellitus (T2DM).

Schmerzen zählen zu den belastendsten Stimuli, denen ein Kind während eines Krankenhausaufenthalt... more Schmerzen zählen zu den belastendsten Stimuli, denen ein Kind während eines Krankenhausaufenthalts ausgesetzt sein kann. Bis vor einiger Zeit wurden sie als unabdingbarer Teil der Behandlung angesehen und sogar häufig ignoriert. 1968 stellte Swaford fest, dass lediglich 2 von 60 pädiatrischen Patienten nach einem viszeralen Eingriff Schmerzmittel benötigten, und schloss daraus, "pediatric patients seldom need medication for the relief of pain. They tolerate discomfort well. The child will say he does not feel well or that he is uncomfortable, that he wants his parents but often he will not relate this unhappiness to pain." Damals galten Neugeborene zudem als schmerzunempfindlich .

Eplasty, 2010

This report describes a case where 4 digits were replanted in a mentally retarded patient with a ... more This report describes a case where 4 digits were replanted in a mentally retarded patient with a history of smoking and the inability to follow postoperative arrangements.

Journal of pediatric surgery, 2014

Comparison of the outcome of newborns with simple (sGS) and complex gastroschisis (cGS: gastrosch... more Comparison of the outcome of newborns with simple (sGS) and complex gastroschisis (cGS: gastroschisis with atresia, necrosis, perforation or volvulus). We conducted a systematic database search, quality assessment and meta-analyzed relevant articles which evaluated the mortality and morbidity of newborns with cGS versus sGS. Risk ratios (RR) with 95% confidence interval (CI) were reported for categorical data, and the mean difference (MD) was calculated for continuous data. Pooled estimates of RR and MD were computed using generic inverse variance and a random-effects model. Of 19 identified reports, 13 eligible studies were included. The mortality of infants with cGS (16.67%) was significantly higher than sGS (2.18%, RR: 5.39 [2.42, 12.01], p<0.0001). Significantly different outcome was found for the following parameters: Infants with cGS are started on enteral feedings later and they take longer to full enteral feedings with a subsequent longer duration of parenteral nutrition....

European Journal of Pediatric Surgery, 2015

Background Implementation of complex fetoscopic procedures that included intracorporeal suturing ... more Background Implementation of complex fetoscopic procedures that included intracorporeal suturing has been limited due to technical difficulties that might be surmounted with adequate training. Evaluating the impact of laparoscopic or fetoscopic training on fetoscopic performance was the aim of this study. Methods To evaluate fetoscopic performance after either laparoscopic or fetoscopic training, subjects were asked to perform four surgeon&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s square knots fetoscopically prior and post 2 hours of hands-on training. All subjects were medical students and novice in laparoscopic and fetoscopic interventions. Total time, knot stability (evaluated via tensiometer), suture accuracy, knot quality, and fetoscopic performance were assessed. Results Forty-six subjects were included in the study; after simple randomization, 24 were trained fetoscopically and 22 laparoscopically. Both groups had comparable baseline characteristics and improved after training significantly regarding all aspects assessed in this study. Subjects who trained fetoscopically were superior in terms of suturing and knot-tying performance. Conclusion Training significantly improves fetoscopic performance and may indeed be the keystone for future complex fetoscopic interventions. It seems advisable to train rather fetoscopically than laparoscopically resulting in higher suture and knot-tying quality.

Surgical Endoscopy, 2011

Background Gastroschisis is a malformation consisting of an abdominal wall defect with eviscerate... more Background Gastroschisis is a malformation consisting of an abdominal wall defect with eviscerated bowel. Its standard treatment is postnatal repositioning or temporary prosthetic bag placement. The aim of our study is to evaluate the feasibility of its fetoscopic management in a lamb model. Methods At mid-gestation (day 75), gastroschisis was created in eight German blackhead sheep. A second fetoscopic procedure was performed on day 105, assessing the viability, extension, and potential for repositioning of eviscerated bowel. The fetus was retrieved by Cesarean section on day 132 and evaluated. Results In six fetuses gastroschisis could be successfully created and assessed with fetoscopy. Two fetuses were lost due to technical complications. Primary repair by repositioning the intestine into the abdomen was not possible because it grew into an inflammatory conglomerate too large for the small fetal abdominal cavity. Conclusions Although technically demanding, we were able to produce and reassess six cases of gastroschisis by fetoscopy. As primary repositioning appears unfavorable, fetoscopic prosthetic bag placement may become an alternative.

European Journal of Pediatric Surgery, 2014

Background Prospective data of transumbilically laparoscopic-assisted appendectomies (TULAA) is a... more Background Prospective data of transumbilically laparoscopic-assisted appendectomies (TULAA) is absent in the pediatric population. We therefore compared the midterm outcome of TULAA with open (OA) and laparoscopic (LA) appendectomies in children with appendicitis in a matched prospective study. Methods A total of 20 patients operated with TULAA were matched to 20 cases operated by LA and OA, respectively, according to sex, age, and histology of the resected appendix. All 60 children were evaluated during a 3-month follow-up visit. Results The subjective pain level after discharge, the rate of complications, and persistent painful wound as well as the duration of days refraining from school or kindergarten were similar in all three groups. The wound satisfaction was significantly higher in TULAA and LA. Children operated with TULAA had a faster return to full physical activity compared with OA. Conclusion Our data suggest that TULAA, LA, and OA have a similar outcome 3 months after surgery apart from cosmetic appearance of the wound and return to full physical activity in pediatric patients. Whether parental bias or the increased wound satisfaction act as confounders for early return to full physical activity should be evaluated in larger prospective randomized trials.

INTRODUCTION Skin lacerations are common in children and their repair is a very unpleasant exper... more INTRODUCTION Skin lacerations are common in children and their repair is a very unpleasant experience for a child. While pain management has been recognized as a key element of high-quality patient care, recent studies report that pain management in the pediatric emergency departments is still suboptimal. Lidocaine-epinephrine-tetracaine (LET) gel could potentially improve the traumatic experience caused by skin repair as it obviates the need for infiltration. Thus, the aim of the current study was to compare local eutectic mixture of local anesthetics (EMLA) plus mepivacaine infiltration with topical anesthetics (LET-gel). MATERIALS AND METHODS Prospective, propensity score-matched multicenter study including all children between 3 and 16 years presented at two centers. After anesthetics (LET vs. EMLA and infiltration) standardized skin repair was performed. Pain assessment was performed using the faces pain rating scale or visual analogue scale. Follow-up, performed 2 weeks afte...

Frontiers in Immunology

BackgroundNeutrophils are the first responders in wound healing after injury that mediate pro- an... more BackgroundNeutrophils are the first responders in wound healing after injury that mediate pro- and anti-inflammatory activities i.a. through the formation of extracellular traps (NETs). However, excessive NETs presence in wound tissue can cause local hyperinflammation and -coagulation resulting in delayed wound healing. To improve wound healing, we aimed to examine the role of NETs and DNase1 on primary and secondary wound healing.MethodsThe study included 93 C57BL/6 mice, with 3 different genotypes: wildtype, Pad4-, and DNase1-Knockout (KO). Pad4-KO mice show limited NETs formation, while DNase1-KO mice cannot disintegrate them. All 3 genotypes were included in (1) a laparotomy group and (2) a thermal injury group. Animals in both groups either received DNase1 or a vehicle i.p. post wound induction and wound assessment and euthanasia were conducted. Laparotomy and burn scars were assessed using the stony brook scar evaluation scale and modified Yeong scale respectively. Tissue was ...

Scientific Reports

Appendicitis is one of the most frequent emergencies in pediatric surgery, yet current biomarkers... more Appendicitis is one of the most frequent emergencies in pediatric surgery, yet current biomarkers for diagnosis are unspecific and have low predictive values. As neutrophils and extracellular traps (ETs) are an essential component of the immune defense against bacterial infections, and appendicitis is considered an inflammation reaction of the appendix, we hypothesized that neutrophil activation and NET formation play an essential role in appendicitis development and maintenance. Therefore, this pilot study aimed to establish a murine model of appendicitis and to evaluate ETs markers to diagnose appendicitis in mice and humans. The study used 20 (12 appendicitis- and 8 controls) 6-week old mice which underwent advanced appendicitis induction using a modified caecal ligation puncture procedure. During the study, cell-free DNA, neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated Histone H3 (H3cit) were assessed. Additionally, samples of 5 children with histologically co...

Journal of Surgical Research

Steatotic livers are particularly vulnerable to ischemia/reperfusion injury (IRI). One of the rea... more Steatotic livers are particularly vulnerable to ischemia/reperfusion injury (IRI). One of the reasons is an underlying impairment of autophagy. Autophagy is regulated by glycogen synthase kinase 3b (GSK3b) and extracellular signal-regulated kinases (ERK1/2) pathways. Both of them are target proteins of a cell-protective drug, lithium chloride. Lithium chloride treatment reduces IRI in many organs including liver. Therefore, we aimed to investigate the effect of lithium chloride treatment on autophagy induction in steatotic rat livers. We also wanted to evaluate the related cell-protective effects on the enhanced hepatic IRI. After inducing hepatic steatosis, rats were injected with lithium chloride or normal saline for 3 d before being subjected to 70% selective warm ischemia for 60 min. After reperfusion, rats were observed for 30 min, 6, 24, and 48 h. Lithium chloride appeared to protect hepatocytes from IRI via its ability to induce autophagy by modulation of both GSK3b and ERK1/2 pathways. Hepatic damage was significantly decreased in the treatment group as indicated by a reduced inflammatory response, less apoptosis, less necrosis, and lower liver enzyme levels. Simultaneous modulation of GSK3b and ERK1/2 pathways might be an interesting strategy to reduce IRI in steatotic livers with an impairment of autophagy.

Frontiers in Pediatrics

Background: Necrotizing enterocolitis (NEC) is an often-fatal neonatal disease involving intestin... more Background: Necrotizing enterocolitis (NEC) is an often-fatal neonatal disease involving intestinal hyperinflammation leading to necrosis. Despite ongoing research, (1) conflicting results and (2) comorbidities of NEC patients make early NEC detection challenging and may complicate therapy development. Most research suggests that NEC pathogenesis is multifactorial, involving a combination of (1) gut prematurity; (2) abnormal bacterial colonization; and (3) ischemia-reperfusion (I/R) injury. As neutrophil extracellular traps (NETs) partially mediate I/R injury and drive inflammation in NEC, we hypothesized that NETs contribute to NEC development; particularly in cardiac patients.Methods: A retrospective analysis of baseline characteristics, clinical signs, laboratory parameters, and imaging was conducted for surgically verified NEC cases over 10 years. Patients were stratified into two groups: (1) prior medically or surgically treated cardiac disease (cardiac NEC) and (2) no cardiac ...

Frontiers in Pediatrics

Introduction: Testicular torsion (TT) is a common emergency that warrants immediate exploration t... more Introduction: Testicular torsion (TT) is a common emergency that warrants immediate exploration to prevent infertility or testicular loss. To improve diagnostic reliability, various scoring systems have been published. The aim of this study was to evaluate and validate different testicular torsion scores in a large cohort of children with acute scrotum.Methods: Retrospective analysis of all male children that were admitted for acute scrotum at the Pediatric Surgery Department of the Altonaer Kinderkrankenhaus and University medical Center Hamburg-Eppendorf from 01/2013 to 03/2019. Two testicular torsion scores (Boettcher Alert Score, Testicular Workup for Ischemia and Suspected Torsion Score) were applied to all data sets. Furthermore, an artificial intelligence (AI)-based score was developed and compared to the two current scores.Results: In total, 460 boys were included in the study. Of those, 48 (10.4%) had TT. Children with TT suffered most often from short duration of pain, nau...

Scientific Reports

Various research models to induce necrotizing enterocolitis (NEC) in animals exist, yet significa... more Various research models to induce necrotizing enterocolitis (NEC) in animals exist, yet significant differences in NEC severity between murine animal models and human patients persist. One possible explanation for the difference in severity may be the variance in neutrophil concentration among newborn humans (50-70%) in comparison to neonatal mice (10-25%). However, neutrophil activity has yet to be evaluated in NEC pathogenesis. Thus, the aim of the study was to evaluate the effects of altered neutrophil concentrations in neonatal mice while simultaneously undergoing a NEC induction. A total of 44 neonatal mice were included in this study and 40 were subjected to an established NEC induction paradigm and 4 were assigned a sham group. Of the 40 mice, 30 received granulocytecolony stimulating factor (G-CSF) on a daily basis, while 10 were used as controls (receiving inactivated G-CSF). Mice undergoing G-CSF treatment were further divided into two subgroups: (1) wildtype and (2) ELANE-knockout (KO). ELANE-KO mice are incapable of producing neutrophil elastase (NE) and were used to evaluate the role of neutrophils in NEC. For each of the groups, the following metrics were evaluated: survival, NEC severity, tissue damage, neutrophil count and activation, and NETs formation. An improved murine model of NEC was developed using (1) Lipopolysaccharides and Neocate gavage feeding, (2) hypoxia, and (3) G-CSF administration. The results suggest that the addition of G-CSF resulted in significantly elevated NEC manifestation rates with consequent tissue damage and intestinal inflammation, without affecting overall mortality. Animals without functioning NE (ELANE-KO) appeared to have been protected from NEC development. This study supports the importance of neutrophils in NEC pathogenesis. The optimized NEC induction paradigm, using G-CSF administration, resulted in elevated neutrophil counts, resembling those of neonatal humans. Elevation of neutrophil levels significantly improved NEC disease manifestation by modeling human physiology more accurately than current NEC models. Thus, in the future, murine NEC experiments should include the elevation of neutrophil levels to improve the transition of research findings from mice to humans.

Frontiers in Pediatrics

Introduction: Early-onset sepsis in neonates potentially results in substantial morbidity and mor... more Introduction: Early-onset sepsis in neonates potentially results in substantial morbidity and mortality. A key player in sepsis a neutrophil extracellular traps (NETs) to limit dissemination of pathogens. Aim of this study was to evaluate markers of NET formation in umbilical cord blood as a predictor of neonatal sepsis. Methods: Prospective study including term and preterm neonates. Umbilical cord blood samples were obtained immediately after birth and following markers of inflammation and NET formation were assessed: complete blood count, C-reactive protein (CRP), interleukin 6 (IL-6), levels of cell-free DNA (cfDNA), neutrophil elastase (NE), and myeloperoxidase (MPO). The study population included neonates with confirmed early-onset sepsis and propensity score matched controls. Results: Umbilical cord blood samples of 491 neonates were obtained, of whom 17 neonates (n = 17) presented clinical and laboratory signs of infection within the first 72 h postpartum. Seventeen neonates without infection were matched as controls. IL-6 differed significantly between both groups, whereas other infection parameters such as CRP and neutrophil levels, and in particular the NET surrogate markers (cfDNA, NE, MPO), did not show any significant differences. Conclusion: NET markers in umbilical cord blood appear to not predict the onset of neonatal sepsis. These findings probably result from the neonates' inability or delayed ability to form NETs, which is suspected to be a main reason for the increased risk of severe infections in neonates, but is also assumed to prevent negative NET-mediated consequences during perinatal adaptation.

While pooled loss- and gain-of-function screening approaches have become increasingly popular to ... more While pooled loss- and gain-of-function screening approaches have become increasingly popular to systematically investigate mammalian gene function, they have thus far ignored the fact that cell populations are heterogeneous. Here we introduce multi-level barcoded sgRNA libraries to (i) monitor differences in the behavior of multiplexed clonal cell lines, (ii) trace sub-clonal lineages of cells expressing the same sgRNA, (iii) derive in-sample screen replicates and (iv) reduce the number of cells and sequencing read counts required to reach statistical significance. Using our approach, we illustrate how clonal heterogeneity impairs the results of pooled genetic screens and demonstrate the ability of multi-level barcoding to resolve cellular heterogeneity related issues.

Journal of Robotic Surgery

Bju International, Nov 1, 2013

International Journal of Environmental Research and Public Health

Parents caring for children with rare diseases fear the long-term progression of the child’s dise... more Parents caring for children with rare diseases fear the long-term progression of the child’s disease. The current study aims to systematically investigate the quality of life (QoL) in parents of children with different rare diseases. We performed a systematic literature search including quantitative studies on QoL of parents caring for children and adolescents with rare diseases in five databases (APA PsycArticles, APA PsycInfo, MEDLINE, PSYNDEXplus, and PubMed) published between 2000–2020. Of the 3985 titles identified, 31 studies met the inclusion criteria and were selected for narrative review. Studies were included if they investigated predictors of parental QoL or reported QoL compared to normative samples, parents of healthy children, or children with other chronic diseases. We used the Newcastle–Ottawa Scale to assess methodological quality. The systematic review revealed that parents of children with rare diseases experience reduced QoL compared to parents with healthy child...