Anastomotic leakage following rectal cancer laparoscopic surgery: can a transanal drainage tube be an alternative to diverting stoma?

OBJECTIVE: Anastomosis leakage in laparoscopic surgery for rectal cancer is still a serious problem affecting the patient's treatment outcome. This study aimed to evaluate the role of a transanal drainage tube compared with a diverting stoma in reducing the rate of anastomosis leakage and limiting surgical complications. PATIENTS AND METHODS: A retrospective study was conducted on 196 rectal cancer patients undergoing laparoscopic low anterior resection from July 2018 to October 2022 at 108 Central Military Hospital. The transanal drainage tube was placed in 133 patients (group A), and diverting stoma was performed in 63 patients (group B). RESULTS: There was no difference between the two groups regarding age, sex, comorbidities, distance from the tumor to the anal verge, and preoperative stage. The amount of blood loss, the method of performing the anastomosis, and the distance from the anastomosis to the anal verge did not differ between the two groups. However, the surgical time was longer in the group with diverting stoma (138.3 ± 25.1 minutes vs. 127.6 ± 31 minutes, p = 0.018). The rate of anastomosis was not significantly different between groups A and B (8.3% in group A and 7.9% in group B, p = 0.936). The proportion of patients with anastomosis requiring reoperation in group A was higher than in group B. However, the difference was not statistically significant (8/11 patients in group A and 2/5 patients in group B, p = 0.29). CONCLUSIONS: Placing a transanal drainage tube in laparoscopic surgery for rectal cancer to reduce the rate of anastomosis can be considered an alternative method for diverting stoma with complications related to the stoma.

[Intravesical oxybutynin treatment for neurogenic detrusor overactivity : Efficacy and safety data from clinical practice with the first intravesical oxybutynin treatment authorized in Germany]. / Intravesikale Oxybutynin-Behandlung der neurogenen Detrusorüberaktivität : Wirksamkeits- und Sicherheitsdaten aus der Praxis der ersten in Deutschland zugelassenen intravesikalen Oxybutynin-Behandlung.

Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cm H2O ± 26.12 standard deviation (SD) to 21.07 cm H2O ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects.

Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs.

A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states is delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death is over, chondroprogenitor differentiation is accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlates with, and is necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.

Features of trastuzumab-related cardiac dysfunction: deformation analysis outside left ventricular global longitudinal strain.

Background: Cancer therapy-related cardiac dysfunction due to trastuzumab has been well-known for many years, and echocardiographic surveillance is recommended every 3 months in patients undergoing trastuzumab treatment, irrespective of the baseline cardiotoxicity risk. However, the potential harm and cost of overscreening in low- and moderate-risk patients have become great concerns. Objectives: This study aimed to identify the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the behaviours of left and right heart deformations during trastuzumab chemotherapy in low- and moderate-risk patients. Methods: We prospectively enrolled 110 anthracycline-naïve women with breast cancer and cardiovascular risk factors who were scheduled to receive trastuzumab. The left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS), and right ventricular and left atrial longitudinal strains were evaluated using echocardiography at baseline, before every subsequent cycle and 3 weeks after the final dose of trastuzumab. The baseline risk of CTRCD was graded according to the risk score proposed by the Heart Failure Association (HFA) Cardio-Oncology Working Group and the International Cardio-Oncology Society (ICOS). CTRCD and its severity were defined according to the current European Society of Cardiology (ESC) guidelines. Results: Twelve (10.9%) patients had asymptomatic CTRCD. All CTRCD occurred sporadically during the first 9 months of the active trastuzumab regimen in both low- and moderate-risk patients. While CTRCD was graded as moderate severity in 41.7% of patients and heart failure therapy was initiated promptly, no irreversible cardiotoxicity or trastuzumab interruption was recorded at the end of follow-up. Among the left and right heart deformation indices, only LV-GLS decreased significantly in the CTRCD group during the trastuzumab regimen. Conclusions: CTRCD is prevalent in patients with non-high-risk breast cancer undergoing trastuzumab chemotherapy. Low- and moderate-risk patients show distinct responses to trastuzumab. The LV-GLS is the only deformation index sensitive to early trastuzumab-related cardiac dysfunction.

Assessment of bowel movement dysfunction following laparoscopic low anterior resection for rectal cancer: a single-center study from Vietnam.

OBJECTIVE: Postoperative bowel movement dysfunction is a challenging problem greatly affecting patients' quality of life after low anterior resection. We aimed to evaluate the bowel movement function of patients undergoing laparoscopic low anterior resection for rectal cancer. PATIENTS AND METHODS: This retrospective study recruited 82 rectal cancer patients undergoing laparoscopic low anterior resection from July 2018 to July 2020 at 108 Military Central Hospital, Hanoi, Vietnam. RESULTS: The patients' mean age was 62.3±11.6 (28-84) years, 54 (65.9%) were males, and 28 (34.1%) were females. Bowel movement function changed significantly after one year: the average score for low anterior resection syndrome (LARS) after three months, six months, and one year was 17.6, 14.0, and 10.6, respectively. The rate of patients with major LARS decreased from 26.8% after three months to 14.6% after one year. The Wexner score also decreased from 5.9 after three months to 3.4 after one year. The rate of patients with normal bowel movement increased from 28.0% after three months to 46.3% after one year. The rate of patients with complete fecal incontinence decreased from 11.0% after three months to 7.3% after one year. Preoperative chemoradiotherapy (p=0.017), tumor location (p=0.02), method of anastomosis (p=0.01), and anastomosis location (p=0.000) were risk factors associated with major LARS after surgery. CONCLUSIONS: Bowel movement dysfunction in rectal cancer patients undergoing laparoscopic low anterior resection is a common and persistent problem after surgery. However, bowel function gradually recovers over time. Therefore, patients should be monitored and supported for a better quality of life.

How do forms and characteristics of Asian public housing neighbourhoods affect dementia risk among senior population? A cross-sectional study in Hong Kong.

BACKGROUND: Public housing estate is a key determinant of community health risk in American/European cities. However, how forms/characteristics of compact/hilly public housing's neighbourhoods affect dementia among Asian seniors was underestimated. DESIGN: This was a cross-sectional study. METHODS: A total of 2,077 seniors living in Hong Kong's public housing estates were included. Dementia was measured by a Cantonese version of Montreal - Cognitive Assessment. Built environment was measured based on three dimensions (greenery, walkability, accessibility), including 11 metrics. Circular buffers (without walking paths) and service areas (considering walking paths) with two-dimensional/three-dimensional (terrain) adjustment were applied to quantify forms/characteristics of neighbourhoods. Two spatial buffers were applied: immediate distance (200 m) and walkable distance (500 m). Exposure-by-exposure regressions were applied to evaluate the associations between form/characteristics of neighbourhood and dementia. RESULTS: Forms/characteristics without considering walking paths may overestimate health benefits from built environment. For circular buffers, higher percentage of building coverage, higher land use mix and more community/transportation/leisure facilities were negatively associated with dementia. All measures of greenery were positively associated with dementia. For service areas, measures of walkability and accessibility became insignificant except more community facilities at the immediate distance. Furthermore, terrain effect was insignificant when it was compared with the impacts of walking paths. CONCLUSION: Dementia among seniors in hilly public housing estates was negatively associated with neighbourhood's walkability and accessibility and was influenced by walking paths. For healthy ageing, improved forms/characteristics of public housing neighbourhoods should include more accessible spaces and community facilities along walking paths for physical activities and basic daily needs.

Estimation of Total Body Surface Area Burned: A Comparison Between Burn Unit and Referring Facilities.

Accuracy of burn size estimation is critical in acute burn management because it directly affects the patient's outcome and prognosis. This study aims to quantify the discrepancies of total body surface area (TBSA) burned between the burn unit (TBSAb) and the referring facilities (TBSAr). Data of all referred adult and paediatric patients admitted to the Hospital Universiti Sains Malaysia Burn Unit within 24 hours post burn were retrospectively reviewed from 2015 to 2019. %TBSA discrepancies were calculated by the differences between TBSAb and TBSAr. A total of 208 patients (111 adults and 97 paediatric patients) were recruited in this study. Of these, the TBSA was overestimated in 60.58% cases, underestimated in 13.46% cases, accurate in 7.69% cases, and in 18.27% cases the referrals had no TBSAr stated. The %TBSA discrepancy was the highest in severe burns (mean 10.80% in adults and 7.59 in paediatric patients; P<0.001). The time interval between referral and reassessment and patients' body mass index (BMI) were not statistically significant for the magnitude of TBSA discrepancy. The number of burn areas involved correlated with the %TBSA discrepancies, with the highest recorded discrepancy being 21.50% in whole body involvement. There were significant discrepancies in TBSA estimations between the referring facilities and those of the Hospital Universiti Sains Malaysia (USM) burn unit, especially among the paediatric patients and those with severe burns. Implementation of educational programs by burn care experts and agreement on a universal method of TBSA assessment are necessary in reducing the discrepancies.

L'estimation précise de la surface brûlée est cruciale dans la prise en charge des patients. Cette étude a évalué les différences d'évaluation de SB selon sa réalisation en CTB (CTB) ou ailleurs (A). Les données de tous les patients (111 adultes et 97 enfants) hospitalisés entre 2015 et 2019, dans les 24h suivant leur brûlure, dans le CTB du CHU Universiti Sains Malaysia ont été revues rétrospectivement. L'estimation A n'était correcte que dans 7,69% des cas. Elle était exagérée dans 60,58% des cas, minorée dans 13,46% et absente dans 18,27%. L'erreur était plus nette (10,8% chez les adultes, 7,59% chez les enfants) en cas de brûlure grave. Le BMI et la durée entre les évaluations A et CTB n'entraient pas en ligne de compte. L'erreur augmentait avec le nombre de régions touchées, pour atteindre 21,5% si toutes comportaient une brûlure. Ces constatations nous amènent à proposer des actions d'éducation dispensées par des brûlologues et l'acceptation par tous d'une méthode unique de calcul de la SB.

Association between awareness of vulnerability and disaster preparedness in an infrastructure-resilient city: a population-based study.

OBJECTIVES: Factors associated with an individual's awareness of vulnerability can be modified by the infrastructure of a city. These factors may impact disaster preparedness among local populations in an infrastructure-resilient city, which further influences the health risks of various population subgroups. STUDY DESIGN: This was a population-based study. METHODS: Four population subgroups, which have previously been reported to be related to awareness of vulnerability (i.e. past experiences, sociodemographic deprivation, poor housing conditions and family medical needs), were analysed for their impacts on disaster preparedness. Validated population-based phone interviews (n = 856) were conducted in Hong Kong. Three types of disaster preparedness were studied: (1) physical preparedness; (2) social preparedness; and (3) education preparedness. RESULTS: Previous experience of social hazards, accidental hazards and epidemics increased disaster preparedness among the local population. Specifically, experiences of accidental hazards and social hazards were positively associated with physical preparedness (odds ratios 1.626, 95% confidence interval [95% CI] 1.215, 2.172) and 1.501 [95% CI 1.114, 2.024], respectively). However, experiences of natural hazards did not increase preparedness, even in Hong Kong, which is a city with high 'disaster resilience' because of its well-developed infrastructure. Moreover, individuals with a low educational level or low income had lower education preparedness, unmarried individuals had lower social preparedness, and poor housing conditions of non-private-housing households had negative associations with education preparedness. These findings partially align with local disaster responses to the 2018 Typhoon Mangkhut, the 2019 social unrest and the 2020 COVID-19 pandemic, all of which were observed after the 2018 survey reported in this study. CONCLUSIONS: Social and environmental interventions should be targeted to marginalised subpopulations through location-based community strategies to encourage increased environmental knowledge and participation in disaster preparedness activities.

Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case-control study.

BACKGROUND: Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early-life infections remains unclear. OBJECTIVE: To investigate the impact of early-life infections on AD development. METHODS: This population-based nested case-control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early-life infections and subsequent AD by conditional stepwise logistic regression analysis. RESULTS: Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P < 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29-1.51], skin infections (aOR, 1.55; 95% CI, 1.40-1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55-1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0-1, 1-2 and >2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure. CONCLUSION: Infections in early life are associated with AD development in infancy and early childhood.

Sensorineural Hearing Loss in Nasopharyngeal Carcinoma Survivors in the Modern Treatment Era - The Early and Late Effects of Radiation and Cisplatin.

AIMS: Hearing loss is a common debilitating complication in nasopharyngeal carcinoma (NPC) survivors. The aim of the present study was to investigate the impact of inner ear/cochlear radiation dose and cisplatin use on early and late sensorineural hearing loss (SNHL) in NPC patients treated with radiotherapy alone, concurrent chemoradiation (cCRT) and induction chemotherapy followed by cCRT (iCRT) in the intensity-modulated radiotherapy era. MATERIALS AND METHODS: The study included 81 NPC patients treated with intensity-modulated radiotherapy between 2014 and 2016. Pure tone audiometry was carried out at baseline and follow-up. The effects of cochlear/inner ear radiation and cisplatin doses on early (<12 months) and late (≥24 months) SNHL were analysed using multivariable regression after adjusting for important predictors. RESULTS: In total, 156 ears were examined. In early SNHL (n = 136), cisplatin use predicted the incidence of early high-frequency SHNL (HF-SNHL) (odds ratio 6.4, 95% confidence interval 1.7-23.9, P = 0.005). Ninety ears were analysed for late SNHL (median follow-up 38 months). Inner ear/cochlear radiation and cisplatin doses and better pre-treatment hearing were independent predictors of threshold change at 4 kHz. Every 10 Gy increase in inner ear/cochlear Dmean resulted in 5-dB and 6-dB threshold changes, respectively (cochlear Dmean: B = 0.005, 95% confidence interval 0.0004-0.009, P = 0.031; inner ear Dmean: B = 0.006, 95% confidence interval 0.001-0.010, P = 0.014). Cisplatin use was associated with late HF-SNHL (odds ratio 3.74, 95% confidence interval 1.1-12.3, P = 0.031). In the cCRT and iCRT subgroups, no cisplatin dose-dependent ototoxicity was observed. Severe (≥30 dB) late HF-SNHL occurred in 14% and 25% of the patients when the cochlear dose constraints were 40 Gy and 44 Gy, respectively. The radiotherapy-alone group did not develop severe late HF-SNHL. CONCLUSION: Cochlear/inner ear radiation dose and cisplatin use showed differential and independent ototoxicity in early and late SNHL. As cochlear/inner ear dose-dependent ototoxicity was demonstrated, the cochlear dose constraint should be as low as reasonably achievable, especially when cisplatin is also administered.

Real-world results of immune checkpoint inhibitors from the Taiwan National Health Insurance Registration System.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are a major advance in cancer treatment, but their payment benefits are unclear, resulting in financial risk. In Taiwan, the National Health Insurance Administration (NHIA) has adapted risk-sharing mechanisms to cover ICIs by collecting and assessing real-world evidence, such as case registration data, to adjust benefit packages for each medication, increase payment benefits of ICIs, and enable national health insurance sustainability. PATIENTS AND METHODS: This nationwide, multicenter, retrospective cohort study assessed the real-world use, effectiveness, and safety of ICIs reimbursed by the NHIA for treating multiple advanced cancers in Taiwan. We obtained data mainly from the NHIA Immune Checkpoint Inhibitor Registry Database. RESULTS: Between April 1, 2019, and March 31, 2020, 1644 patients received at least one dose of ICIs. The overall response rate (RR) was 29.1%. The metastatic urothelial carcinoma of patients ineligible for chemotherapy showed the highest RR. The estimated median progression-free survival (PFS) was 2.8 months (95% confidence interval [CI]=2.7-3 months), and renal cell carcinoma showed the longest PFS. The median PFS was reached in patients with most cancers except classic Hodgkin's lymphoma, which had a small sample size. The estimated survival probability was 50%. CONCLUSIONS: Under the national registration tracking system, Taiwan's high-cost drug policy has enabled access to new medicines and maximized patient benefits.

Patency of permanent vascular access creation in paediatric patients with end stage renal disease.

Renal transplant is the first-line therapy in paediatric patients with end-stage renal disease (ESRD). Wong HS and Goh BL reported up to 79% of 1061 paediatric patients still require long-term haemodialysis (HD).1 The lack of deceased and living donors is attributable to the poor awareness, cultural and religious grounds. Permanent vascular access (PVA) in paediatrics therefore, serves more as a long term treatment rather than a bridging therapy. We observed 5 children and an adolescent, all with previous indwelling catheters, who underwent arteriovenous fistula (AVF) creation and report the outcomes. The aim of this report is to determine the factors that influence the longterm patency of paediatric AVF. Factors such as body weight, vessel diameter, preoperative preparations, microsurgical technique and postoperative maintenance are discussed. In addition, considerations on the choice and timing of PVA is highlighted.

Spatially-resolved pharmacokinetic/pharmacodynamic modelling of bystander effects of a nitrochloromethylbenzindoline hypoxia-activated prodrug.

PURPOSE: Hypoxia-activated prodrugs (HAPs) have the potential for eliminating chemo- and radiation-resistant hypoxic tumour cells, but their activity is often compromised by limited penetration into hypoxic zones. Nitrochloromethylbenzindoline (nitroCBI) HAPs are reduced in hypoxic cells to highly cytotoxic DNA minor groove alkylating aminoCBI metabolites. In this study, we investigate whether a lead nitroCBI, SN30548, generates a significant bystander effect through the diffusion of its aminoCBI metabolite and whether this compensates for any diffusion limitations of the prodrug in tumour tissue. METHODS: Metabolism and uptake of the nitroCBI in oxic and anoxic cells, and diffusion through multicellular layer cultures, was characterised by LC-MS/MS. To quantify bystander effects, clonogenic cell killing of HCT116 cells was assessed in multicellular spheroid co-cultures comprising cells transfected with cytochrome P450 oxidoreductase (POR) or E. coli nitroreductase NfsA. Spatially-resolved pharmacokinetic/pharmacodynamic (PK/PD) models, parameterised by the above measurements, were developed for spheroids and tumours using agent-based and Green's function modelling, respectively. RESULTS: NitroCBI was reduced to aminoCBI by POR under anoxia and by NfsA under oxia, and was the only significant cytotoxic metabolite in both cases. In spheroid co-cultures comprising 30% NfsA-expressing cells, non-metabolising cells were as sensitive as the NfsA cells, demonstrating a marked bystander effect. Agent-based PK/PD models provided good prediction of cytotoxicity in spheroids, while use of the same parameters in a Green's function model for a tumour microregion demonstrated that local diffusion of aminoCBI overcomes the penetration limitation of the prodrug. CONCLUSIONS: The nitroCBI HAP SN30548 generates a highly efficient bystander effect through local diffusion of its active metabolite in tumour tissue.

A systematic review of behaviour analytic interventions for young children with intellectual disabilities.

BACKGROUND: According to several comprehensive systematic and narrative reviews, interventions based on applied behaviour analysis principles, or behaviour analytic interventions, are considered evidence based for children with autism spectrum disorder (ASD). However, no comprehensive review of the literature related to behaviour analytic interventions for children with intellectual disability (ID) currently exists. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (registration ID: CRD42018099317), the purpose of this study was to conduct a systematic review of the relevant published literature on the use of behaviour analytic interventions to develop skills in young children (0-8 years) with ID (and without ASD). A preliminary search of the literature identified 1209 potential studies published between January 2000 and April 2020. The review process resulted in 48 articles consisting of 49 studies (i.e. one paper contained two studies) that met the inclusion criteria. Most used single-case research designs. Studies were evaluated on five dimensions of methodological quality based on the Scientific Merit Rating Scale developed by the National Autism Center (NAC). The NAC definitions were also used for the quantity and quality of research evidence required for interventions to be considered established or emerging. RESULTS: There were a number of limitations to the quality of the body of research. Nevertheless, various behaviour analytic interventions met criteria for being established interventions when used for targeting communication, adaptive and pre-academic skills in young children with ID. Behaviour analytic interventions targeting academic skills met criteria for emerging interventions. CONCLUSIONS: Although the current literature is limited, results indicate that behaviour analytic interventions may be effectively used to support skill development in children with ID.

Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness.

Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2-49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2-9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42-49 (95% confidence interval (CI) 52-92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06-1.50, P = 0.010).

Computational modelling for the spiral flow in umbilical arteries with different systole/diastole flow velocity ratios.

The systole/diastole (S/D) flow velocity ratios in umbilical arteries (UAs) have been used to assess the health status of the feto-placental circulation, yet its connection to the morphology of UAs, specifically its coiling pattern remains unclear. Spiral flow induces unbalanced wall shear stress (WSS) distribution in UAs, and may contribute to the uneven arterial wall thickness, and the chirality. In this paper, we use a 3D computational fluid dynamics (CFD) technique to quantify the wall shear stress (WSS) in UA models of two configurations, i.e. at 0.17 and 0.50 spirals per centimeter, to represent normo- and hyper-coiling, respectively. For CFD simulations we use two different S/D ratios (3.02 and 5.70) revealed from the ultrasonography waveforms of a normal and an intrauterine growth restriction (IUGR) case. We found that more coils in the UA model enhanced WSS throughout a cardiac cycle (up to 24%) with the same inflow condition. In addition, time-averaged WSS are generally increased and more uneven in the hyper-coiling model. We suggest that the large WSS difference between the peak systole and end diastole (62% higher in the IURG case than the normal case) may induce uneven stenosis distribution at UAs, and contribute to UA chirality.