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Abstract: Malignant basaloid neoplasms of the skin are frequent, and their accurate diagnosis holds paramount importance for treatment and prognosis. However, these neoplasms can present diagnostic challenges because of their extensive differential diagnosis, which encompasses cutaneous metastasis among many other possibilities. We present a case of a 74-year-old man with a history of p16-positive palatine tonsil squamous cell carcinoma (SCC) treated with surgery and adjuvant radiation with no prior evidence of recurrence who presented to the dermatologist with 2 chin papules. The initial histopathologic evaluation of these lesions showed poorly differentiated malignant basaloid neoplasms. Subsequently, these biopsies were compared with the previous biopsies from his tonsil and lymph node, which showed similar findings including positive p16 staining and positive molecular testing for human papillomavirus-16, confirming the diagnosis of cutaneous metastasis from his previously diagnosed human papillomavirus-related tonsil SCC. Additional imaging studies found metastases to internal organs including the brain, and he was started on chemotherapy, immunotherapy, and radiation therapy. Cutaneous metastases from tonsil SCC are exceedingly rare, and only 5 cases have been described. Furthermore, this is the first case confirming the presence of high-risk human papillomavirus by molecular studies within the cutaneous metastases. The presented case underscores the importance of recognizing this unusual manifestation of tonsil SCC metastatic to the skin along with a good clinical patient history, ensuring accurate and prompt diagnosis and treatment of this condition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels., Methods: We assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure-response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH., Findings: We estimate that 1·4 (95% CI 1·3-1·5) million deaths and 74 (68-80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65-0·72), 0·14 (0·13-0·17) for acute respiratory infections, and 0·10 (0·09-0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH., Interpretation: WASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns., Funding: WHO and Foreign, Commonwealth & Development Office., Competing Interests: Declaration of interests JW reports grants from UK Foreign, Commonwealth & Development Office (FCDO), during this study. MB reports grants from Bill & Melinda Gates Foundation during this study. CFL reports non-financial support from WHO COVID-19 Vaccine Effectiveness Working Group, grants from CureVac AG, grants from PATH, grants from HilleVax, and personal fees from Valneva outside the submitted work. JB reports grants from Bill & Melinda Gates Foundation, grants from US Centers for Disease Control & Prevention, and grants from Columbia World Projects during this study. MCF reports Consulting for Rickett's Global Scientific Advisory Committee. RBJ reports grants from UK FCDO during this study, grants from Agence française de développement, grants from Australian Government Department of Foreign Affairs and Trade, grants from Austrian Development Agency, grants from Bill & Melinda Gates Foundation, grants from German Federal Ministry for Economic Development and Cooperation, grants from The Netherlands Directorate-General for International Cooperation, grants from Swiss Agency for Development and Cooperation, and grants from United States Agency for International Development outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 World Health Organization. Published by Elsevier Ltd. All rights reserved. This is an Open Access article published under the CC BY 3·0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs)., Methods: In this systematic review and meta-analysis, we updated previous reviews following their search strategy by searching MEDLINE, Embase, Scopus, Cochrane Library, and BIOSIS Citation Index for studies of basic WASH interventions and of WASH interventions providing a high level of service, published between Jan 1, 2016, and May 25, 2021. We included randomised and non-randomised controlled trials conducted at household or community level that matched exposure categories of the so-called service ladder approach of the Sustainable Development Goal (SDG) for WASH. Two reviewers independently extracted study-level data and assessed risk of bias using a modified Newcastle-Ottawa Scale and certainty of evidence using a modified Grading of Recommendations, Assessment, Development, and Evaluation approach. We analysed extracted relative risks (RRs) and 95% CIs using random-effects meta-analyses and meta-regression models. This study is registered with PROSPERO, CRD42016043164., Findings: 19 837 records were identified from the search, of which 124 studies were included, providing 83 water (62 616 children), 20 sanitation (40 799 children), and 41 hygiene (98 416 children) comparisons. Compared with untreated water from an unimproved source, risk of diarrhoea was reduced by up to 50% with water treated at point of use (POU): filtration (n=23 studies; RR 0·50 [95% CI 0·41-0·60]), solar treatment (n=13; 0·63 [0·50-0·80]), and chlorination (n=25; 0·66 [0·56-0·77]). Compared with an unimproved source, provision of an improved drinking water supply on premises with higher water quality reduced diarrhoea risk by 52% (n=2; 0·48 [0·26-0·87]). Overall, sanitation interventions reduced diarrhoea risk by 24% (0·76 [0·61-0·94]). Compared with unimproved sanitation, providing sewer connection reduced diarrhoea risk by 47% (n=5; 0·53 [0·30-0·93]). Promotion of handwashing with soap reduced diarrhoea risk by 30% (0·70 [0·64-0·76])., Interpretation: WASH interventions reduced risk of diarrhoea in children in LMICs. Interventions supplying either water filtered at POU, higher water quality from an improved source on premises, or basic sanitation services with sewer connection were associated with increased reductions. Our results support higher service levels called for under SDG 6. Notably, no studies evaluated interventions that delivered access to safely managed WASH services, the level of service to which universal coverage by 2030 is committed under the SDG., Funding: WHO, Foreign, Commonwealth & Development Office, and National Institute of Environmental Health Sciences., Competing Interests: Declaration of interests JW and BG report grants from the UK Foreign, Commonwealth and Development Office, during the conduct of the study. SH reports grants from the National Institute of Environmental Health Sciences, during the conduct of the study. MB reports grants from Bill & Melinda Gates Foundation during the conduct of the study. BFA reports grants from National Institutes of Health, and grants and non-financial support from Bill & Melinda Gates Foundation, outside the submitted work. MCF reports personal fees from Reckitt, outside the submitted work. AM has received funding as a statistical consultant on The Lancet Commission on water, sanitation and hygiene, and health to analyse the associations between water, sanitation, hygiene, and handwashing and child health using Multiple Indicator Cluster Survey data and to complete an individual-participant data meta-analysis of WASH trials on pathogen contamination in the environment and child health. All other authors declare no competing interests., (Copyright © 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Purpose of Review: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most critical public health challenge in recent history. In this report, we present a case of suspected acute hemorrhagic encephalitis with bilateral intracranial hemorrhages associated with coronavirus disease 2019 (COVID-19) infection., Recent Findings: A 48-year-old female COVID-19-positive patient developed acute changes in her neurologic status. A head CT with CT angiography demonstrated extensive bilateral parietal and occipital intraparenchymal hemorrhage with intraventricular extension and acute hydrocephalus. The patient was treated with an external ventricular drain, and a CSF sample was tested for SARS-CoV-2 but was found to be negative., Summary: The underlying mechanism for developing acute hemorrhagic encephalitis in viral illnesses may be autoimmune in nature and warrants further investigation. The initial neurologic presentation of COVID-19-related hemorrhagic encephalitis is altered level of consciousness, which may prompt further neurologic examination and imaging to exclude this feature., (© 2020 American Academy of Neurology.)

Background: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners., Main Body: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health., Conclusion: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden.

Porous biomaterials can be additively manufactured with micro-architecture tailored to satisfy the stringent mechano-biological requirements imposed by bone replacement implants. In a previous investigation, we introduced structurally porous biomaterials, featuring strength five times stronger than commercially available porous materials, and confirmed their bone ingrowth capability in an in vivo canine model. While encouraging, the manufactured biomaterials showed geometric mismatches between their internal porous architecture and that of its as-designed counterpart, as well as discrepancies between predicted and tested mechanical properties, issues not fully elucidated. In this work, we propose a systematic approach integrating computed tomography, mechanical testing, and statistical analysis of geometric imperfections to generate statistical based numerical models of high-strength additively manufactured porous biomaterials. The method is used to develop morphology and mechanical maps that illustrate the role played by pore size, porosity, strut thickness, and topology on the relations governing their elastic modulus and compressive yield strength. Overall, there are mismatches between the mechanical properties of ideal-geometry models and as-manufactured porous biomaterials with average errors of 49% and 41% respectively for compressive elastic modulus and yield strength. The proposed methodology gives more accurate predictions for the compressive stiffness and the compressive strength properties with a reduction of the average error to 11% and 7.6%. The implications of the results and the methodology here introduced are discussed in the relevant biomechanical and clinical context, with insight that highlights promises and limitations of additively manufactured porous biomaterials for load-bearing bone replacement implants., Statement of Significance: In this work, we perform mechanical characterization of load-bearing porous biomaterials for bone replacement over their entire design space. Results capture the shift in geometry and mechanical properties between as-designed and as-manufactured biomaterials induced by additive manufacturing. Characterization of this shift is crucial to ensure appropriate manufacturing of bone replacement implants that enable biological fixation through bone ingrowth as well as mechanical property harmonization with the native bone tissue. In addition, we propose a method to include manufacturing imperfections in the numerical models that can reduce the discrepancy between predicted and tested properties. The results give insight into the use of structurally porous biomaterials for the design and additive fabrication of load-bearing implants for bone replacement., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The accuracy of Additive Manufacturing processes in fabricating porous biomaterials is currently limited by their capacity to render pore morphology that precisely matches its design. In a porous biomaterial, a geometric mismatch can result in pore occlusion and strut thinning, drawbacks that can inherently compromise bone ingrowth and severely impact mechanical performance. This paper focuses on Selective Laser Melting of porous microarchitecture and proposes a compensation scheme that reduces the morphology mismatch between as-designed and as-manufactured geometry, in particular that of the pore. A spider web analog is introduced, built out of Ti-6Al-4V powder via SLM, and morphologically characterized. Results from error analysis of strut thickness are used to generate thickness compensation relations expressed as a function of the angle each strut formed with the build plane. The scheme is applied to fabricate a set of three-dimensional porous biomaterials, which are morphologically and mechanically characterized via micro Computed Tomography, mechanically tested and numerically analyzed. For strut thickness, the results show the largest mismatch (60% from the design) occurring for horizontal members, reduces to 3.1% upon application of the compensation. Similar improvement is observed also for the mechanical properties, a factor that further corroborates the merit of the design-oriented scheme here introduced., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

AbstractUnderstanding illness costs associated with diarrhea and acute respiratory infections (ARI) could guide prevention and treatment strategies. This study aimed to determine incidence of childhood diarrhea and ARI and costs of homecare, hospitalization, and outpatient treatment by practitioner type in rural Bangladesh. From each of 100 randomly selected population clusters we sampled 17 households with at least one child < 5 years of age. Childhood diarrhea incidence was 3,451 and ARI incidence was 5,849/1,000 child-years. For diarrhea and ARI outpatient care per 1,000 child-years, parents spent more on unqualified ($2,361 and $4,822) than qualified health-care practitioners ($113 and $947). For outpatient care, visits to unqualified health-care practitioners were at least five times more common than visits to qualified practitioners. Costs for outpatient care treatment by unqualified health-care practitioners per episode of illness were similar to those for qualified health-care practitioners. Homecare costs were similar for diarrhea and ARI ($0.16 and $0.24) as were similar hospitalization costs per episode of diarrhea and ARI ($35.40 and $37.76). On average, rural Bangladeshi households with children < 5 years of age spent 1.3% ($12 of $915) of their annual income managing diarrhea and ARI for those children. The majority of childhood illness management cost comprised visits to unqualified health-care practitioners. Policy makers should consider strategies to increase the skills of unqualified health-care practitioners, use community health workers to provide referral, and promote homecare for diarrhea and ARI. Incentives to motivate existing qualified physicians who are interested to work in rural Bangladesh could also be considered.

Purpose: Renal autotransplantation is an infrequently performed procedure. It has been used to manage complex ureteral disease, vascular anomalies and chronic kidney pain. We reviewed our 27-year experience with this procedure., Materials and Methods: This is a retrospective, observational study of 51 consecutive patients who underwent renal autotransplantation, including 29 at Oregon Health and Science University between 1986 and 2013, and 22 at Virginia Mason Medical Center between 2007 and 2012. Demographics, indications, operative details and followup data were collected. Early (30 days or less) and late (greater than 30 days) complications were graded according to the Clavien-Dindo system. Factors associated with complications and pain recurrence were evaluated using a logistic regression model., Results: The 51 patients underwent a total of 54 renal autotransplants. Median followup was 21.5 months. The most common indications were loin pain hematuria syndrome/chronic kidney pain in 31.5% of cases, ureteral stricture in 20.4% and vascular anomalies in 18.5%. Autotransplantation of a solitary kidney was performed in 5 patients. Laparoscopic nephrectomy was performed in 23.5% of cases. Median operative time was 402 minutes and median length of stay was 6 days. No significant difference was found between preoperative and postoperative plasma creatinine (p = 0.74). Early, high grade complications (grade IIIa or greater) developed in 14.8% of patients and 12.9% experienced late complications of any grade. Two graft losses occurred. Longer cold ischemia time was associated with complications (p = 0.049). Of patients who underwent autotransplantation for chronic kidney pain 35% experienced recurrence and 2 underwent transplant nephrectomy. No predictors of pain recurrence were identified., Conclusions: The most common indications for renal autotransplantation were loin pain hematuria syndrome/chronic kidney pain, ureteral stricture and vascular anomalies in descending order. Kidney function was preserved postoperatively and 2 graft losses occurred. At a median followup of 13 months pain resolved in 65% of patients who underwent the procedure. Complication rates compared favorably with those of other major urological operations and cold ischemia time was the only predictor of postoperative complications., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

We used a prospective, longitudinal cohort enrolled as part of a program evaluation to assess the relationship between drinking water microbiological quality and child diarrhea. We included 50 villages across rural Bangladesh. Within each village field-workers enrolled a systematic random sample of 10 households with a child under the age of 3 years. Community monitors visited households monthly and recorded whether children under the age of 5 years had diarrhea in the preceding 2 days. Every 3 months, a research assistant visited the household and requested a water sample from the source or container used to provide drinking water to the child. Laboratory technicians measured the concentration of Escherichia coli in the water samples using membrane filtration. Of drinking water samples, 59% (2,273/3,833) were contaminated with E. coli. Of 12,192 monthly follow-up visits over 2 years, mothers reported that their child had diarrhea in the preceding 2 days in 1,156 (9.5%) visits. In a multivariable general linear model, the log10 of E. coli contamination of the preceding drinking water sample was associated with an increased prevalence of child diarrhea (prevalence ratio = 1.14, 95% CI = 1.05, 1.23). These data provide further evidence of the health benefits of improved microbiological quality of drinking water., (© The American Society of Tropical Medicine and Hygiene.)

Background: For patients with low-risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low-risk PCa., Methods: Beginning in 2007, HRQoL data from validated questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND Medical Outcomes Study short-form survey) were collected by the Center for Prostate Disease Research in a multicenter national database. Patients aged ≤75 years who were diagnosed with low-risk PCa and elected RP or AS for initial disease management were followed for 3 years. Mean scores were estimated using generalized estimating equations adjusting for baseline HRQoL, demographic characteristics, and clinical patient characteristics., Results: Of the patients with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis revealed that patients in the RP group had significantly worse sexual function, sexual bother, and urinary function at all time points compared with patients in the AS group. Differences in mental health between groups were below the threshold for clinical significance at 1 year., Conclusions: In this study, no differences in mental health outcomes were observed, but urinary and sexual HRQoL were worse for patients who underwent RP compared with those who underwent AS for up to 3 years. These data offer support for the management of low-risk PCa with AS as a means for postponing the morbidity associated with RP without concomitant declines in mental health., (© 2015 American Cancer Society.)

Introduction: The impact of transrectal ultrasound guided prostate needle biopsy on erectile dysfunction remains uncertain. We examined whether transrectal ultrasound guided prostate needle biopsy contributes to the development or worsening of erectile dysfunction as assessed by IIEF-5 scores in patients who underwent multiple prostate needle biopsies., Methods: The study population consisted of 826 men who underwent transrectal ultrasound guided 10 to 12-core prostate needle biopsy for suspicion or surveillance of prostate cancer. Men were evaluated for erectile dysfunction using the IIEF-5 questionnaire. Erectile dysfunction was modeled as a categorical variable, defined as any (0 to 20), mild (16 to 20), mild to moderate (11 to 15), moderate (6 to 10) or severe (0 to 5). The impact of multiple prostate needle biopsies was also evaluated., Results: Of 826 men who underwent prostate needle biopsy 240 (29%) had undergone 1 or more and 168 (20%) had undergone 2 or more biopsies. Mean patient age was 63 years and mean IIEF-5 score was 16. On univariate analysis age (OR 1.11, 95% CI 1.09-1.14, p <0.001), and 1 (OR 1.79, 95% CI 1.06-3.03, p=0.03) or 2 (OR 1.80, 95% CI 1.02-3.17, p=0.04) prior prostate needle biopsies were associated with erectile dysfunction. On multivariate analysis age alone was predictive of severe erectile dysfunction (OR 1.09, 95% CI 1.05-1.12, p=0.002). A repeat prostate needle biopsy within 12 months was associated with worse erectile dysfunction (OR 1.55, 95% CI 1.08-2.93, p=0.02). When long-term erectile function was evaluated, prostate needle biopsy was not significant after adjustment for covariates., Conclusions: In the short term prostate needle biopsy may be important in predicting transient (less than 1 year) erectile dysfunction. However, in the long term prostate needle biopsy does not predict erectile dysfunction in aging men.