Fetal lower urinary tract obstruction: international Delphi consensus on management and core outcomes set.

OBJECTIVE: To reach a Delphi-generated international expert consensus on the diagnosis, prognostic, management, and core outcome set (COS) of fetal Lower Urinary Tract Obstruction (LUTO). METHODS: A three-round Delphi procedure was conducted among an international panel of LUTO experts. The panel was provided with a list of literature review-generated parameters for the diagnosis, prognostic, management, and outcomes. A parallel procedure was conducted along with patient groups during the development of COS. RESULTS: A total of 160 experts were approached, of whom 99 completed the first round and 80 (80/99, 80.8%) completed all three rounds. In the first trimester, an objective measurement of longitudinal bladder diameter (with ≥7 mm being abnormal) should be used to suspect LUTO. In the second trimester, imaging parameters of LUTO could include: a) an enlarged bladder, b) a keyhole sign, c) bladder wall thickening, d) bilateral hydro (uretero) nephrosis, and e) male sex. There was a lack of consensus on the current prognostic scoring literature. However, experts agreed on the value of amniotic fluid volume (< 24 weeks) to predict survival and that the value of fetal intervention is to improve neonatal survival. While experts endorsed the role of sonographic parameters of renal dysplasia, at least one vesicocentesis, and urine biochemistry for prognosis and counseling, these items did not reach a consensus for determining fetal intervention candidacy. On the other hand, imaging parameters suggestive of LUTO, absence of life-limiting structural or genetic anomalies, gestational age of ≥16 weeks, and oligohydramnios defined as deepest vertical pocket (DVP) <2 cm should be used as candidacy criteria for fetal intervention based on experts' consensus. If a bladder refill was evaluated, it should be assessed subjectively. Vesicoamniotic shunt should be the first line of fetal intervention. In the presence of suspected fetal renal failure, serial amnioinfusion should only be offered as an experimental procedure under research protocols. The core outcome set for future studies was agreed upon. CONCLUSION: International consensus on the diagnosis, prognosis, and management of fetal LUTO, as well as the Core Outcome Set, should inform clinical care and research to optimize perinatal outcomes. This article is protected by copyright. All rights reserved.

Association of Intrinsic Capacity with Frailty, Physical Fitness and Adverse Health Outcomes in Community-Dwelling Older Adults.

BACKGROUND: Intrinsic capacity (IC) and frailty are complementary in advancing disability prevention through maintaining functionality. OBJECTIVES: We examined the relationship between IC and frailty status at baseline and 1-year, and evaluated if IC decline predicts frailty onset among robust older adults. The secondary objectives investigated associations between IC, physical fitness and health-related outcomes. DESIGN: Prospective cohort study. SETTING: Community-based assessments. PARTICIPANTS: Older adults aged>55 years, who were independent in ambulation (walking aids permitted). MEASUREMENTS: 5 domains of IC were assessed at baseline: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Composite IC (0-10) was calculated, with higher scores representing greater IC. Frailty status was based on modified Fried criteria, with frailty progression defined as incremental Fried score at 1-year. RESULTS: 809 participants (67.6+6.8 years) had complete data for all 5 IC domains. 489 (60.4%) participants were robust but only 213 (26.3%) had no decline in any IC domain. Pre-frail and frail participants were more likely to exhibit decline in all 5 IC domains (p<0.05), with decremental composite IC [9 (8-9), 8 (6-9), 5.5 (4-7.5), p<0.001] across robust, prefrail and frail. IC was significantly associated with fitness performance, independent of age and gender. Higher composite IC reduced risk for frailty progression (OR=0.62, 95% CI 0.48-0.80), and reduced frailty onset among robust older adults (OR=0.53, 95% CI 0.37-0.77), independent of age, comorbidities and social vulnerability. Participants with higher IC were less likely to experience health deterioration (OR=0.70, 95% CI 0.58-0.83), falls (OR=0.76, 95% CI 0.65-0.90) and functional decline (OR=0.64, 95% CI 0.50-0.83) at 1-year. CONCLUSION: Declining IC may present before frailty becomes clinically manifest, increasing risk for poor outcomes. Monitoring of IC domains potentially facilitates personalized interventions to avoid progressive frailty.

Perceived hazardous physical work environments and job-related affective well-being of navy officers aboard the Republic of Korea Navy ships and submarines in South Korea.

INTRODUCTION: Navy ships and submarines are important military measures that protect the Republic of Korea. They also comprise naval officers' workplace. However, few studies have examined naval officers' working environment and their job-related well-being. This study aimed to explore exposure to hazardous work environments among navy officers aboard ships and submarines and their association with job-related affective well-being. METHODS: This was a cross-sectional descriptive study. The sample comprised 146 officers from 4 navy ships and 98 officers from 5 submarines. Items of exposure to the eight types of hazardous work environments and the Job-related Affective Well-being Scale (JAWS) were included in the self-report survey questionnaires. RESULTS: The most common hazards reported by officers aboard navy ships were vibration (63.7%) and air pollution (56.2%). For submarine officers, these hazards were lack of personal space (72.4%) and air pollution (67.3%). The average JAWS score for ship officers and submarine officers was 69.81 (SD=10.89) and 70.50 (SD=10.83), respectively. For ship officers, exposure to air pollution, noise, vibration, thermal discomfort during summer or winter and lack of personal space were significantly correlated with lower JAWS scores. For submarine officers, exposure to fire, burning or electrical shock, air pollution, noise, thermal discomfort during summer or winter and lack of personal space were significantly correlated with lower JAWS scores. CONCLUSIONS: This study revealed that some naval officers aboard ships or submarines are exposed to hazardous work environments. Moreover, certain types of hazardous work environments were associated with naval officers' job-related affective well-being.

Microsurgery for intracranial aneurysms: A qualitative survey on technical challenges and technological solutions.

Introduction: Microsurgery for the clipping of intracranial aneurysms remains a technically challenging and high-risk area of neurosurgery. We aimed to describe the technical challenges of aneurysm surgery, and the scope for technological innovations to overcome these barriers from the perspective of practising neurovascular surgeons. Materials and Methods: Consultant neurovascular surgeons and members of the British Neurovascular Group (BNVG) were electronically invited to participate in an online survey regarding surgery for both ruptured and unruptured aneurysms. The free text survey asked three questions: what do they consider to be the principal technical barriers to aneurysm clipping? What technological advances have previously contributed to improving the safety and efficacy of aneurysm clipping? What technological advances do they anticipate improving the safety and efficacy of aneurysm clipping in the future? A qualitative synthesis of responses was performed using multi-rater emergent thematic analysis. Results: The most significant reported historical advances in aneurysm surgery fell into five themes: (1) optimising clip placement, (2) minimising brain retraction, (3) tissue handling, (4) visualisation and orientation, and (5) management of intraoperative rupture. The most frequently reported innovation by far was indocyanine green angiography (84% of respondents). The three most commonly cited future advances were hybrid surgical and endovascular techniques, advances in intraoperative imaging, and patient-specific simulation and planning. Conclusions: While some surgeons perceive that the rate of innovation in aneurysm clipping has been dwarfed in recent years by endovascular techniques, surgeons surveyed highlighted a broad range of future technologies that have the potential to continue to improve the safety of aneurysm surgery in the future.

Bulevirtide for HBV and HDV infections.

Hepatitis B virus (HBV) and its satellite virus hepatitis D (HDV) are common worldwide hepatotrophic infections responsible for cirrhosis and hepatocellular carcinoma (HCC). The more common HBV infection has several therapeutic regimens currently available for suppression of viral replication. However, a regimen leading to an effective sustained functional cure is still not available. In contrast, HDV infection, which causes the most severe form of chronic viral hepatitis and an increased rate of HCC, currently has no Food and Drug Administration (FDA)-approved treatment. Bulevirtide is a novel virion entry inhibitor which blocks the virion's hepatocyte pathway of entry, the hepatic sodium/taurocholate cotransporting polypeptide (NTCP) receptor, and is now a promising therapy for both infections. In July 2020 bulevirtide was authorized for use in the E.U. following a positive opinion by the European Medicines Agency (EMA) for the treatment of chronic HDV infection in HDV RNA-positive adult patients with compensated liver disease. In this paper we have examined the studies that led to this approval as well as studies examining the drug's efficacy in treating HBV.

FISHing for 1p19q codel in oligodendroglioma.

Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.

Dominant-negative NFKBIA mutation promotes IL-1ß production causing hepatic disease with severe immunodeficiency.

Although IKK-ß has previously been shown as a negative regulator of IL-1ß secretion in mice, this role has not been proven in humans. Genetic studies of NF-κB signaling in humans with inherited diseases of the immune system have not demonstrated the relevance of the NF-κB pathway in suppressing IL-1ß expression. Here, we report an infant with a clinical pathology comprising neutrophil-mediated autoinflammation and recurrent bacterial infections. Whole-exome sequencing revealed a de novo heterozygous missense mutation of NFKBIA, resulting in a L34P IκBα variant that severely repressed NF-κB activation and downstream cytokine production. Paradoxically, IL-1ß secretion was elevated in the patient's stimulated leukocytes, in her induced pluripotent stem cell-derived macrophages, and in murine bone marrow-derived macrophages containing the L34P mutation. The patient's hypersecretion of IL-1ß correlated with activated neutrophilia and liver fibrosis with neutrophil accumulation. Hematopoietic stem cell transplantation reversed neutrophilia, restored a resting state in neutrophils, and normalized IL-1ß release from stimulated leukocytes. Additional therapeutic blockade of IL-1 ameliorated liver damage, while decreasing neutrophil activation and associated IL-1ß secretion. Our studies reveal a previously unrecognized role of human IκBα as an essential regulator of canonical NF-κB signaling in the prevention of neutrophil-dependent autoinflammatory diseases. These findings also highlight the therapeutic potential of IL-1 inhibitors in treating complications arising from systemic NF-κB inhibition.

The affect of personality traits and decision-making style on postoperative quality of life and distress in patients undergoing pelvic exenteration.

AIM: Our aim was to identify whether personality traits and decision-making styles affect quality of life (QoL) outcomes and levels of psychological distress following pelvic exenteration (PE). METHOD: Patients undergoing PE between 2008 and 2015 were identified from a prospectively maintained database at a single quaternary referral centre. Patients were invited to complete two validated questionnaires, with the Big Five inventory being used to assess personality traits and the Melbourne Decision Making Questionnaire to determine decision-making style. Data on QoL outcomes and distress from the prospectively established database were utilized. QoL with respect to both physical and mental health components was measured using Short Form 36 version 2 (SF-36v2) and the Functional Assessment of Cancer Therapy - Colorectal (FACT-C). Distress was measured using the Distress Thermometer. Postoperative pain scores were also measured using SF-36v2. RESULTS: Of the 93 patients eligible for participation, 42 returned the study questionnaire. On multivariate analysis, neuroticism was the most significant predictor of poorer QoL and increased levels of distress, consistent across all of the measures utilized and at the different time points used. Other personality traits showed an isolated statistically significant impact upon QoL. There were no significant findings with respect to decision-making style. Apart from neuroticism, the most significant predictor of QoL was the number of major complications for the patient. CONCLUSION: Patients demonstrating neurotic personality traits show poorer QoL outcomes and higher levels of distress following PE. Identification of these patients would allow targeted pre- and postoperative intervention to improve outcomes following PE.

Quality of life and functional outcomes following pelvic exenteration and sacrectomy.

AIM: The aim was to compare postoperative quality of life (QOL) between patients undergoing pelvic exenteration (PE) and pelvic exenteration with sacrectomy (PES), and to investigate the influence of high (L5-S2) vs low (≤ S3) sacrectomy on QOL and functional outcomes. METHOD: Patients undergoing en bloc sacrectomy as part of a PE and PE alone from 2008 to 2015 were identified from a prospectively maintained database. QOL and functional outcomes were assessed using the 36-Item Short Form Survey, the European Organization for Research and Treatment of Cancer Colorectal Cancer questionnaire and Quality of Life questionnaire, the Revised Musculoskeletal Tumour Scale, the Lower Extremity Functional Scale, the Sexual Health Inventory for Men and the Female Sexual Function Index. RESULTS: Of the 344 patients identified, data were available for 116 patients who underwent PE alone and 140 patients who underwent PES. PES patients had significantly poorer physical component scores (P < 0.001) but not mental component scores (P = 0.17). Of the 140 PES patients, 55 were eligible and were invited to participate in a second functional survey, with 30 patients returning the study questionnaire. High sacrectomy patients, compared with low sacrectomy, had significantly worse lower limb motor function (P = 0.03) and poorer physical (P = 0.001) and mental health component scores (P = 0.02). No differences were found in sexual, bladder and bowel function between high and low sacrectomy patients. CONCLUSIONS: Patients undergoing PES had worse physical component scores compared with PE alone, whereas high sacrectomy patients had significantly worse lower limb motor function and physical and mental component scores but comparable bowel, bladder and sexual functional outcomes compared with low sacrectomy patients.

Adenoviral Infections in Singapore: Should New Antiviral Therapies and Vaccines Be Adopted?

BACKGROUND: A number of serious human adenovirus (HAdV) outbreaks have been recently reported: HAdV-B7 (Israel, Singapore, and USA), HAdV-B7d (USA and China), HAdV-D8, -D54, and -C2 (Japan), HAdV-B14p1 (USA, Europe, and China), and HAdV-B55 (China, Singapore, and France). METHODS: To understand the epidemiology of HAdV infections in Singapore, we studied 533 HAdV-positive clinical samples collected from 396 pediatric and 137 adult patients in Singapore from 2012 to 2018. Genome sequencing and phylogenetic analyses were performed to identify HAdV genotypes, clonal clusters, and recombinant or novel HAdVs. RESULTS: The most prevalent genotypes identified were HAdV-B3 (35.6%), HAdV-B7 (15.4%), and HAdV-E4 (15.2%). We detected 4 new HAdV-C strains and detected incursions with HAdV-B7 (odds ratio [OR], 14.6; 95% confidence interval [CI], 4.1-52.0) and HAdV-E4 (OR, 13.6; 95% CI, 3.9-46.7) among pediatric patients over time. In addition, immunocompromised patients (adjusted OR [aOR], 11.4; 95% CI, 3.8-34.8) and patients infected with HAdV-C2 (aOR, 8.5; 95% CI, 1.5-48.0), HAdV-B7 (aOR, 3.7; 95% CI, 1.2-10.9), or HAdV-E4 (aOR, 3.2; 95% CI, 1.1-8.9) were at increased risk for severe disease. CONCLUSIONS: Singapore would benefit from more frequent studies of clinical HAdV genotypes to identify patients at risk for severe disease and help guide the use of new antiviral therapies, such as brincidofovir, and potential administration of HAdV 4 and 7 vaccine.

Serratia marcescens in the neonatal intensive care unit: A cluster investigation using molecular methods.

BACKGROUND: Serratia marcescens (S. marcescens) is associated with nosocomial infections with significant morbidity and mortality in the neonatal intensive care units (NICU). We describe the control of a multi-clonal S. marcescens infections outbreak in our tertiary-level NICU and the application of molecular typing using repetitive element palindromic PCR (rep-PCR) and next generation sequencing (NGS) in the investigation. METHODS: Outbreak investigation was performed where clinical, spatial and epidemiologic links were established. Screening of all infants in the NICU and the environment was performed. Rep-PCR and NGS methods were used to identify potential environmental sources of infections and clustering among cases. RESULTS: Eleven cases were detected during the outbreak period: mean gestational age 27 weeks (range: 24-32), predominantly male (82%), mean age of infection 24 days (range: 6-51). Six infants were treated for conjunctivitis and one for bacteraemia. Identification of colonized infant via a point prevalence survey and cohorting of all infected/colonized patients were implemented. We performed environmental swabbing of surfaces, water outlets, chlorhexidine hand wash solutions and hand hygiene hand rubs. Both rep-PCR and NGS classified the 11 case isolates into 5 types. No point source was identified except for a single positive environmental isolate from a sink which was clonally distinct from the cases. CONCLUSION: Identification and cohorting of infected/colonized patient was important in the control of S. marcescens outbreak in the NICU. The utility of rep-PCR was comparable to NGS in providing molecular information to develop S. marcescens outbreak control strategies.

Screening for microsatellite instability in colorectal carcinoma: Practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting.

Since 2014, the National Comprehensive Cancer Network (NCCN) has recommended that colorectal carcinoma (CRC) be universally tested for high microsatellite instability (MSI-H) which is present in 15% of such cancers. Fidelity of resultant microsatellites during DNA replication is contingent upon an intact mismatch repair (MMR) system and lack of fidelity can result in tumourigenesis. Prior to commencing routine screening for MSI-H, we assessed two commonly used methods, immunohistochemical (IHC) determination of loss of MMR gene products viz MLH1, MSH2, MSH6 and PMS2 against PCR amplification and subsequent fragment analysis of microsatellite markers, BAT25, BAT26, D2S123, D5S346 and D17S250 (Bethesda markers) in 73 unselected primary CRC. 15.1% (11/73) were categorized as MSI-H while deficient MMR (dMMR) was detected in 16.4% (12/73). Of the dMMR, 66.7% (8/12) were classified MSI-H, while 33.3% (4/12) were microsatellite stable/low microsatellite instability (MSS/MSI-L). Of the proficient MMR (pMMR), 95.1% (58/61) were MSS/MSI-L and 4.9% (3/61) were MSI-H. The κ value of 0.639 (standard error =0.125; p = 0.000) indicated substantial agreement between detection of loss of DNA mismatch repair using immunohistochemistry and the detection of downstream microsatellite instability using PCR. After consideration of advantages and shortcomings of both methods, it is our opinion that the choice of preferred technique for MSI analysis would depend on the type of laboratory carrying out the testing.

Efficacy of electromotive drug administration in delivering botulinum toxin a in children with neuropathic detrusor overactivity-outcomes of a pilot study.

BACKGROUND: Intravesical botulinum toxin A (BtA) injection is well established in managing paediatric neuropathic detrusor overactivity (NDO). Electromotive drug administration (EMDA) is a less invasive method, which can be performed in the clinic, using pulsed electrical current for drug delivery via a urethral catheter. Few small studies report good outcomes following BtA via EMDA (BtA/EMDA) into bladders of children with NDO. OBJECTIVE: The objective of this study is to assess the efficacy of BtA/EMDA in children with NDO, reduced bladder capacity and compliance. METHODS: Twelve children with NDO on baseline urodynamic study were prospectively included. Pre-BtA/EMDA and post-BtA/EMDA results compared the following four parameters: maximal cystometric capacity, bladder compliance, maximal detrusor pressure (pDetmax) during detrusor overactivity and pDetmax at capacity. The Wilcoxon matched-pairs signed-rank test using Graphpad Prism 8 was used for analysis. Secondary outcomes include adverse effects and symptomatic improvement. RESULTS: Fourteen episodes of BtA/EMDA were performed. Five patients received 3.3 IU/kg of Botox®, and five received 10 IU/kg (maximum 300 IU). Four patients received 10 IU/kg of Dysport®. Two patients in the Dysport®/EMDA group also received Botox®/EMDA more than six months previously. Thirteen of 14 post-EMDA results were completed and included in the paired analysis. No statistically significant improvements in any cystometric parameters were demonstrated. Eight patients subsequently had intravesical BtA injections with significant improvements in both cystometric parameters and symptoms. Two patients subsequently transitioned to adult services; one was commenced on mirabegron, and one has undergone ileocystoplasty with Mitrofanoff appendicovesicostomy. DISCUSSION: Despite some evidence to support BtA/EMDA in children with NDO, the authors were unable to replicate previously published positive cystometric and symptomatic outcomes. In addition, BtA/EMDA performed poorly when compared with conventional intravesical BtA injections. This implies failure of EMDA to deliver BtA correctly to the target tissue. The large size of the BtA molecule or the abnormal bladder wall in NDO could account for the negative results. Thorough preparation and consultation was undertaken before this study with BtA/EMDA, and it is discouraging that the authors were unable to reproduce the positive results of other groups. CONCLUSIONS: Although safe and acceptable to most patients, the authors cannot recommend the use of BtA/EMDA for NDO in children at present.

Prognostic factors and patterns of failure after surgery for T4 rectal cancer in the beyond total mesorectal excision era.

BACKGROUND: Despite advances in the rates of total mesorectal excision (TME) for rectal cancer surgery, decreased local recurrence rates and increased 5-year survival, there still exists large variation in the quality of treatment received. Up to 30 per cent of rectal cancers are locally advanced at presentation and approximately 5-10 per cent still breach the mesorectal plane and invade adjacent structures despite neoadjuvant therapy. With the evolution of extended resections for rectal cancers beyond the TME plane, proponents advocate that these resections should be performed only in specialist centres. The aim was to assess the prognostic factors and patterns of failure after beyond TME surgery for T4 rectal cancers. METHODS: Data were collected from prospective databases at three high-volume institutions specializing in beyond TME surgery for T4 rectal cancers between 1990 and 2013. The primary outcome measures were overall survival, local recurrence and patterns of first failure. RESULTS: Three hundred and sixty patients were identified. The negative resection margin (R0) rate was 82·8 per cent (298 patients) and the local recurrence rate was 12·5 per cent (45 patients). The type of surgical procedure (Hartmann's: hazard ratio (HR) 4·49, 95 per cent c.i. 1·99 to 10·14; P = 0·002) and lymphovascular invasion (HR 2·02, 1·08 to 3·77; P = 0·032) were independent predictors of local recurrence. The 5-year overall survival rate for all patients was 61 (95 per cent c.i. 55 to 67) per cent. The 5-year cumulative incidence of first failure was 8 per cent for local recurrence, 6 per cent for local and distant disease, and 18 per cent for distant disease. CONCLUSION: This study has demonstrated that a coordinated approach in specialist centres for beyond TME surgery can offer good oncological and long-term survival in patients with T4 rectal cancers.

ANTECEDENTES: A pesar de las mejoras en los porcentajes de extirpación total del mesorrecto (total mesorectal excision, TME) en la cirugía de cáncer de recto, la disminución de los porcentajes de recidiva local y el aumento de la supervivencia a 5 años, todavía existe una gran variabilidad en la calidad del tratamiento recibido. Hasta el 30% de los cánceres de recto están localmente avanzados en el momento del diagnóstico y aproximadamente el 5-10% sobrepasarán el plano mesorrectal e invadirán las estructuras adyacentes a pesar del tratamiento neoadyuvante. Con la evolución de las resecciones ampliadas para los cánceres de recto que sobrepasan el plano de la TME, los defensores recomiendan que estas resecciones solo se realicen en centros especializados. El objetivo fue evaluar los factores pronósticos y los patrones de recidiva después de la cirugía ampliada más allá de la TME para los cánceres de recto T4. MÉTODOS: Los datos se recogieron a partir de bases de datos prospectivas de tres instituciones de alto volumen especializadas en resecciones ampliadas más allá de la TME para el cáncer de recto T4 entre 1990 y 2013. Los criterios de valoración principal fueron la supervivencia global, la recidiva local y los patrones de la primera recidiva. RESULTADOS: Se identificaron 360 pacientes. El margen de resección fue negativo (R0) en el 82,8% (n = 298) y el porcentaje de recidiva local fue de 12,5% (n = 45). El tipo de cirugía realizada (Hartmann: cociente de riesgos instantáneos, hazard ratio, HR 4,49; i.c. del 95%: 1,99-10,14; P = 0,002) y la invasión linfovascular (HR 2,02; i.c. del 95%: 1,08-3,77; P = 0,032) fueron factores predictivos independientes de recidiva local. La supervivencia global a 5 años para todos los pacientes fue del 61% (i.c. del 95%: 55-67). La incidencia acumulada a los 5 años de la primera recidiva fue de 8% para la recidiva local, 6% para la recidiva local y a distancia, y 18% para la recidiva a distancia. CONCLUSIÓN: Este estudio demuestra que un abordaje coordinado en centros especializados para cirugía más allá de la TME puede ofrecer una buena supervivencia oncológica y a largo plazo en pacientes con cáncer de recto T4.

Pushing the boundaries of pelvic exenteration by maintaining survival at the cost of morbidity.

BACKGROUND: Pelvic exenteration (PE) provides a potentially curative option for advanced or recurrent malignancy confined to the pelvis. A clear (R0) resection margin is the strongest prognostic factor predicting long-term survival, driving most technical advances in PE surgery. The aim of this cohort study was to describe changing trends in extent of resection, postoperative complications, mortality and overall survival after PE surgery. METHODS: Consecutive patients who underwent PE for advanced or recurrent pelvic malignancy at a single institution in Sydney, Australia, were identified. The cohort was divided into three groups based on time periods reflecting annual surgical volume: 1994-2006 (20 or fewer procedures per year), 2007-2013 (21-50 procedures per year) and 2014-2017 (over 50 procedures per year). Primary outcomes were extent of resection, postoperative complications, 60-day mortality and 3-year overall survival. Secondary outcomes were patient characteristics, receipt of neoadjuvant therapy and duration of hospital stay. RESULTS: There were increases over time in rates of lateral and posterior compartment resections (P < 0·001), and bony pelvis (P = 0·002) and neurovascular (P < 0·001) excision. For patients undergoing reconstruction, the proportion receiving vertical rectus abdominus myocutaneous flaps increased significantly (P = 0·005). Rates of wound infection, dehiscence, and abdominal and pelvic collections increased over the study interval. Short-term mortality decreased, and 1- and 3-year survival rates improved. CONCLUSION: Technical and surgical advancements have led to more complex PE resections, with R0 and mortality rates improving with higher annual volume. There were associated increases in intraoperative blood loss and postoperative morbidity.

ANTECEDENTES: La exenteración pélvica (pelvic exenteration, PE) ofrece una opción potencialmente curativa para el cáncer localmente avanzado o la recidiva de la neoplasia limitada a la pelvis. Un margen de resección libre (R0) es el factor pronóstico más importante que predice la supervivencia a largo plazo, lo que ha impulsado la mayoría de los avances técnicos en la cirugía de la PE. El objetivo de este estudio de cohortes fue describir el cambio en la tendencia relativa a la extensión de la resección, las complicaciones postoperatorias, la mortalidad y la supervivencia global después de la cirugía de la PE. MÉTODOS: Se identificaron pacientes intervenidos de forma consecutiva a los que se practicó una PE por neoplasia pélvica avanzada o recidivante en una sola institución en Sydney, Australia. La cohorte se dividió en tres grupos según períodos de tiempo que reflejan el volumen quirúrgico anual: 1994-2006 (≤ 20 casos por año), 2007-2013 (21-50 casos por año) y 2014-2017 (> 50 casos por año). Los criterios de valoración principal fueron la extensión de la resección, las complicaciones postoperatorias, la mortalidad a los 60 días y la supervivencia a los tres años. Los criterios de valoración secundarios fueron las características del paciente, la administración de tratamiento neoadyuvante y la duración de la estancia hospitalaria. Las tendencias se evaluaron mediante pruebas de χ2 o ANOVA de una vía. RESULTADOS: Los porcentajes de resección de los compartimentos lateral y posterior, pelvis ósea así como de escisión neurovascular aumentaron con el tiempo (P < 0,01). Entre los pacientes en los que se hizo una reconstrucción, el porcentaje de colgajos miocutáneos verticales del recto del abdomen aumentó significativamente (P = 0,005). Las tasas de infección de herida, dehiscencia y colecciones abdominales y pélvicas aumentaron durante el período de estudio. La mortalidad a corto plazo disminuyó y la supervivencia a 1 y 3 años mejoró durante el período de estudio. CONCLUSIÓN: Los avances técnicos y quirúrgicos han permitido realizar resecciones de PE más complejas, mejorando las tasas de resección R0 y de mortalidad al aumentar el volumen anual de intervenciones. Al mismo tiempo se han observado incrementos en las pérdidas intraoperatorias de sangre, en las reconstrucciones y en la morbilidad postoperatoria.

Do pediatricians routinely perform genitourinary examinations during well-child visits? A review from a large tertiary pediatric hospital.

BACKGROUND: The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. OBJECTIVE: The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. STUDY DESIGN: Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. RESULTS: Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. DISCUSSION: Prior reports suggest 70-75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. CONCLUSIONS: Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.

Sacral nerve stimulation for bowel dysfunction following low anterior resection: a systematic review and meta-analysis.

AIM: Low anterior resection syndrome (LARS) can affect up to 70% of all patients with rectal cancer. In the last two decades, sacral nerve stimulation (SNS) has emerged as an effective treatment for faecal incontinence. There is some encouraging literature on the use of SNS in patients with LARS. The purpose of this review is to provide an up to date review on the utility of SNS on LARS. METHOD: A literature search was conducted using the MEDLINE, Embase and PubMed databases (January 1981-March 2019). Studies identified were appraised with standard selection criteria. Data points were extracted, and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Ten studies met the inclusion criteria and were included in this study. All studies used the Cleveland Clinic Incontinence Score (CCIS), whereas the low anterior resection syndrome score (LARS score) was used in three studies. Overall median improvement in the scoring system was 67.0% (range 35.5%-88.2%) after SNS implantation. There was a significant reduction in CCIS after SNS implantation (mean difference 11.23, 95% confidence interval 9.38-13.07, Z = 11.90, P < 0.00001). The LARS score was also significantly reduced after using SNS in patients with LARS (mean difference 17.87, 95% confidence interval 10.15-25.59, Z = 4.54, P < 0.00001). CONCLUSION: Use of SNS may provide symptomatic benefits for patients with LARS refractory to medical therapy. However, the current level of evidence remains limited. A large multicentre study of SNS for LARS using the validated LARS score is warranted. In addition, the cost-effectiveness of SNS for patients with LARS needs further exploration.

Outcome of fetuses with lower urinary tract obstruction and normal amniotic fluid volume in second trimester of pregnancy.

OBJECTIVE: Congenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end-stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy. METHODS: This was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed. RESULTS: Of the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow-up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1-4) and four (28.6%) had developed end-stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period. CONCLUSIONS: Most fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long-term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late-onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The changing gender landscape of pediatric urology fellowship: results from a survey of fellows and recent graduates.

INTRODUCTION: Women are entering the subspecialty of pediatric urology at an accelerated rate. Gender differences affecting fellowship and job selection have been identified in other fields of medicine. OBJECTIVE: The objective of this study was to understand gender differences in pediatric urology fellowship and job selection and how they may affect the workforce. STUDY DESIGN: A 47-question electronic survey consisting of questions regarding demographics, residency training, and factors influencing fellowship and job selection was distributed to current fellows and recent graduates in pediatric urology in May 2017. RESULTS: A total of 111 recent and current fellows were contacted, and 72% completed the survey (55% female [F] and 45% male [M]; 61% current fellows and 39% recent fellows). Respondents rated factors important in choosing pediatric urology on a scale of 1-5 (1, not important and 5, extremely important), and the top three for both genders were 1-working with children, 2-influential mentors, and 3-bread and butter cases such as inguinal orchiopexy. During residency, 93% of respondents reported having influential mentors in pediatric urology. However, mentorship was more important in fellowship choice for males than females (3.6 F, 4.1 M; P-value = 0.048), and 45% reported having only male mentors. Rating factors important in job choice on a scale of 1-5, respondents reported the top factors as 1-rapport with partners/mentorship (4.5), 2-geography/family preferences (4.3), and 3-participation in mentoring/teaching (3.8). Although most job selection criteria were rated similarly between genders, females rated call schedule higher than males (3.5 F, 2.9 M, P-value = 0.009). Although most females and males (79% of F, 78% of M, P-value = 0.868) sought primarily academic positions, a smaller proportion of females accepted academic positions (52% of F, 72% of M, P-value 0.26), and females reported lower satisfaction regarding the availability of jobs on a scale of 1-5 (1, very dissatisfied and 5, very satisfied; 3.1 F, 3.7 M; P-value = 0.034), particularly in academic positions (3.1 F, 3.7 M; P-value = 0.06). This difference was more pronounced in current fellows than recent graduates and may represent a worsening trend. CONCLUSION: Although significant gender differences in fellowship and job selection may exist in other fields, we found that women and men choose pediatric urology fellowships and jobs using similar criteria, which include work-life balance. Gender differences exist in the influence of mentors, indicating a need for more female mentors. While men and women sought similar types of jobs, women were less satisfied with the availability of jobs, particularly academic jobs, than men, which warrants further investigation.