Diffuse pulmonary arteriovenous malformation presenting with secondary polycythemia and headaches: a case report.

BACKGROUND: Pulmonary arteriovenous malformations are a relatively uncommon medical condition, affecting roughly 1 in every 2500 individuals. Of those suffering from pulmonary arteriovenous malformations, 80% have an underlying genetic condition: hereditary hemorrhagic telangiectasia. CASE PRESENTATION: We present the case of a 20-year-old Pakistani male with a history of persistent slower-onset frontal headaches that increased in severity within the course of the day. His hemoglobin was 18 g/dl, indicating polycythemia, for which he had undergone seven venesections in a month previously. His physical examination was unremarkable. His computed tomography scan depicted multiple dilated tortuous vessels with branching linear opacities in the right lower lobe of the lungs. The multiple feeding arteries were supplied by the right main pulmonary artery, and the large draining veins led to the right inferior pulmonary vein. This was identified as a diffuse pulmonary arteriovenous malformation. He was recommended for a right pulmonary artery angiogram. It showed multiple tortuous vessels with a nidus and large draining veins-features of a diffuse arteriovenous malformation in the right lower lobe of the lung consistent with the computed tomography scan. Embolization of two of these vessels feeding the arteriovenous malformation was conducted, using Amplatzer Vascular plug 2, whereas multiple pushable coils (five coils) were used for embolizing the third feeding vessel. This achieved 70-80% successful embolization of right pulmonary AVM; however, some residual flow was still seen in the arteriovenous malformation given the complexity of the lesion. Immediately after, his oxygen saturation improved from 78% to 96%. CONCLUSION: Diffuse pulmonary arteriovenous malformations, as seen in this patient, are rare, accounting for less than 5% of total pulmonary arteriovenous malformations diagnosed. The patient presented with a complaint of progressive frontal headaches, which can be attributed to low oxygen saturation or the presence of a cerebral arteriovenous malformation. There was no history of hereditary hemorrhagic telangiectasia in the patient's family. Furthermore, although most patients with hereditary hemorrhagic telangiectasia and hence pulmonary arteriovenous malformation have complaints of iron-deficiency anemia, our patient in contrast was suffering from polycythemia. This can be explained as a compensatory mechanism in hypoxemic conditions. Moreover, the patient had no complaint of hemoptysis or epistaxis, giving a varied presentation in comparison with a typical pulmonary arteriovenous malformation.

Factors associated with safe and successful postoperative day 1 discharge after lung operations: a systematic review and meta-analysis.

BACKGROUND: A shorter length of stay (LOS) is associated with fewer hospital-acquired adverse conditions and decreased utilization of hospital resources. While modern perioperative care protocols have enabled some ambitious surgical teams to achieve discharge as early as within postoperative day 1 (POD1), most other teams remain cautious about such an approach due to the perceived risk of missing postoperative complications and increased readmission rates. We aimed to identify factors that would help guide surgical teams aiming for safe and successful POD1 discharge after lung resection. METHODS: We searched the PubMed, Embase, Scopus, Web of Science and CENTRAL databases for articles comparing perioperative characteristics in patients discharged within POD1 (DWPOD1) and after POD1 (DAPOD1) following lung resection. Meta-analysis was performed using a random-effects model. RESULTS: We included eight retrospective cohort studies with a total of 216,887 patients, of which 22,250 (10.3%) patients were DWPOD1. Our meta-analysis showed that younger patients, those without cardiovascular and respiratory comorbidities, and those with better preoperative pulmonary function are more likely to qualify for DWPOD1. Certain operative factors, such as a minimally invasive approach, shorter operations, and sublobar resections, also favor DWPOD1. DWPOD1 appears to be safe, with comparable 30-day mortality and readmission rates, and significantly less postoperative morbidity than DAPOD1. CONCLUSIONS: In select patients with a favorable preoperative profile, DWPOD1 after lung resection can be achieved successfully and without increased risk of adverse outcomes such as postoperative morbidity, mortality, or readmissions.

Risks to Child Development and School Readiness Among Children Under Six in Pakistan: Findings from a Nationally Representative Phone Survey.

This paper analyzes the risks to child development and school readiness among children under age 6 in Pakistan. Drawing on a nationally representative telephone survey conducted in the midst of a global pandemic, between December 2021 and February 2022, we present the first nationally representative estimates of child development for children under 3 years of age and school readiness for children 3-6 years of age, using internationally validated instruments. The paper examines how risk factors that were exacerbated due to the COVID-19 pandemic, such as parental distress, lack of psychosocial stimulation, food insecurity, low maternal education, no enrollment in early childhood education, and living in a rural area, are associated with children's outcomes. The data indicate that more than half (57 percent) of parents with children under age 3 were distressed and that 61 percent of households reported cutting down on the size of or skipping meals since the start of the pandemic. The data reveal that over half of parents fail to engage in adequate psychosocial stimulation with their child and enrollment in early childhood education is very low (39 percent). The paper finds that child development outcomes decline rapidly as the number of risks increase. Specifically, for children under 3 years, lack of psychosocial stimulation at home and higher levels of parental distress were most significantly associated with lower child development levels. For a child aged 3-6 years, early childhood education enrollment and the amount of psychosocial stimulation the child received at home had the strongest association with school readiness scores.

Cet article analyse les risques pour le développement de l'enfant et la maturité scolaire chez les enfants de moins de 6 ans au Pakistan. S'appuyant sur une enquête téléphonique représentative à l'échelle nationale menée pendant une pandémie mondiale entre décembre 2021 et février 2022, nous présentons les premières estimations représentatives au niveau national du développement de l'enfant pour les enfants de moins de 3 ans d'âge et de la maturité scolaire pour les enfants de 3 à 6 ans à l'aide d'instruments validés au niveau international. L'article examine comment les facteurs de risque qui ont été exacerbés en raison de la pandémie COVID-19, tels que la détresse parentale, le manque de stimulation psychosociale, l'insécurité alimentaire, le faible niveau d'éducation maternelle, l'absence d'inscription à l'éducation préscolaire et la vie en zone rurale, sont associés au développement des enfants. Les données indiquent que plus de la moitié (57 %) des parents ayant des enfants de moins de 3 ans étaient en détresse et que 61 % des ménages ont déclaré avoir réduit la taille ou sauté des repas depuis le début de la pandémie. Les données révèlent que plus de la moitié des parents ne s'engagent pas dans une stimulation psychosociale adéquate avec leur enfant et que l'inscription à l'éducation préscolaire est très faible (39 %). L'article constate que les résultats du développement de l'enfant déclinent rapidement à mesure que le nombre de risques augmente. Plus précisément, pour les enfants de moins de 3 ans, le manque de stimulation psychosociale à la maison et des niveaux plus élevés de détresse parentale étaient le plus significativement associés à un plus faible niveaux de développement. Pour un enfant âgé de 3 à 6 ans, l'inscription à l'éducation préscolaire et la quantité de stimulation psychosociale que l'enfant recevait à la maison avaient la plus forte association avec les scores de maturité scolaire.

Este documento analiza los riesgos para el desarrollo infantil y la preparación escolar entre los niños menores de 6 años en Pakistán. Basándonos en una encuesta telefónica representativa a nivel nacional realizada en medio de una pandemia mundial, entre diciembre de 2021 y febrero de 2022, presentamos las primeras estimaciones representativas a nivel nacional del desarrollo infantil de niños menores de 3 años y la preparación escolar de niños de 3 a 6 años de edad, utilizando instrumentos validados internacionalmente. El artículo examina cómo se asocian los factores de riesgo que se exacerbaron debido a la pandemia de COVID-19, como la angustia de los padres, la falta de estimulación psicosocial, la inseguridad alimentaria, la baja educación materna, la no matriculación en educación de primaria infancia y vivir en una zona rural, con los resultados de los niños. Los datos indican que más de la mitad (57 por ciento) de los padres con niños menores de 3 años estaban angustiados y que el 61 por ciento de los hogares informaron que redujeron el tamaño de las comidas o se las saltaron desde el comienzo de la pandemia. Los datos revelan que más de la mitad de los padres no logran dar una estimulación psicosocial adecuada a sus hijos y que la inscripción en la educación de primera infancia es muy baja (39 por ciento). El documento encuentra que los resultados del desarrollo infantil disminuyen rápidamente a medida que aumenta el número de riesgos. Específicamente, para los niños menores de 3 años, la falta de estimulación psicosocial en el hogar y los niveles más altos de angustia de los padres se asociaron de manera más significativa con niveles más bajos de desarrollo infantil. Para un niño de 3 a 6 años, la matriculación en la educación de primera infancia y la cantidad de estimulación psicosocial que el niño recibió en el hogar tuvieron la asociación más fuerte con su puntuación de preparación escolar.

Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa. METHODS: This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants. High-resolution whole exome sequencing (WES) was performed on the Barbadian and Nigerian TNBC samples to identify their mutational profiles and comparisons were made to African American, European American and Asian American sequencing data obtained from The Cancer Genome Atlas (TCGA). Whole exome sequencing was conducted on tumors with an average of 382 × coverage and 4335 × coverage for pooled germline non-tumor samples. RESULTS: Variants detected at high frequency in our WAA cohorts were found in the following genes NBPF12, PLIN4, TP53 and BRCA1. In the TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32% in our cohort; 63% in TCGA-African American; 67% in TCGA-European American; 63% in TCGA-Asian). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-African American cohort. For copy number variants, high frequency alterations were observed in PIK3CA, TP53, FGFR2 and HIF1AN genes. CONCLUSION: This study provides novel insights into the underlying genomic alterations in WAA TNBC samples and shines light on the importance of inclusion of under-represented populations in cancer genomics and biomarker studies.

High triple-negative breast cancer prevalence and aggressive prognostic factors in Barbadian women with breast cancer.

BACKGROUND: Women of African ancestry (WAA) are disproportionately affected by triple-negative breast cancer (TNBC), which remains one of the most clinically challenging breast cancer (BCa) subtypes. This study investigated the prevalence of TNBC and epidemiological trends for BCa in Barbados, a Caribbean island with a high percentage of African ancestry. METHODS: Pathology reports for all BCa cases between 2007 and 2016 were collected from the sole hospital in Barbados and reviewed. The clinicopathological data collected included age, tumor grade, lymph node status, and hormone receptor status as determined by immunohistochemistry. BCa data for non-Hispanic white (NHW) and non-Hispanic black (NHB) American populations were accessed from the Surveillance, Epidemiology, and End Results database. RESULTS: There were 1997 BCa cases in Barbados between 2007 and 2016 for an estimated incidence rate of 135.1 per 100,000 women in Barbados (standardized to the US population, where the standardized incidence rates for NHBs and NHWs were 141.4 and 152.6 per 100,000, respectively). Age-specific incidence rates in Barbados for this period were consistently higher in younger age groups (15-59 years) in comparison with NHWs and NHBs. Between 2010 and 2016 in Barbados, a TNBC prevalence of 25% was observed, whereas TNBC prevalences of 21% and 10% were observed in NHBs and NHWs, respectively. CONCLUSIONS: The BCa incidence was higher in younger Barbadian women than NHWs and NHBs, and the TNBC prevalence was ~2.5 times higher than the prevalence in NHWs. This hints at a possible genetic predisposition and other socioeconomic factors that could explain the high TNBC prevalence and aggressive clinical course in WAA globally.

High-grade Non-small Cell Neuroendocrine Carcinoma of the Esophagus.

High-grade neuroendocrine carcinoma (NEC) of the esophagus is an extremely aggressive and rare disease, which is still not well understood. In this case report, we discuss a 73-year-old male patient that presented with the sole complaint of dysphagia to solid foods. During our evaluation of the patient, a six-centimeter esophageal mass was found on esophagogastroduodenoscopy (EGD). A diagnosis of poorly differentiated (high-grade) non-small cell neuroendocrine carcinoma was made after a histological analysis and immunostaining. We attempted to highlight the diagnosis, evaluation process, and treatment options related to this entity. Our review of the literature revealed that further research is needed, focusing on neuroendocrine carcinomas of the esophagus and how this entity differs from some of the more well-known neuroendocrine neoplasms in terms of management.

Hyperpigmentation with Capecitabine: Part of Hand-Foot Syndrome or a Separate Entity?

Capecitabine has several side effects, most common of which is Hand-Foot syndrome (HFS); however, less frequently reported is capecitabine-associated hyperpigmentation. The hyperpigmentation associated with this drug has been documented to involve the hands and feet and, less commonly, the mucous membranes of the mouth. To our knowledge, it has never been documented to involve the face. We report a case of a patient with capecitabine-induced Hand-Foot Syndrome (HFS), who also presented with hyperpigmentation of the hands, feet, oral mucosa, and face.

Kaiso differentially regulates components of the Notch signaling pathway in intestinal cells.

BACKGROUND: In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso Tg ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut. However, Kaiso's precise role in Notch signaling and whether the Kaiso Tg secretory cell fate phenotype was linked to Kaiso-induced inflammation had yet to be elucidated. METHODS: Intestines from 3-month old Non-transgenic and Kaiso Tg mice were "Swiss" rolled and analysed for the expression of Notch1, Dll-1, Jagged-1, and secretory cell markers by immunohistochemistry and immunofluorescence. To evaluate inflammation, morphological analyses and myeloperoxidase assays were performed on intestines from 3-month old Kaiso Tg and control mice. Notch1, Dll-1 and Jagged-1 expression were also assessed in stable Kaiso-depleted colon cancer cells and isolated intestinal epithelial cells using real time PCR and western blotting. To assess Kaiso binding to the DLL1, JAG1 and NOTCH1 promoter regions, chromatin immunoprecipitation was performed on three colon cancer cell lines. RESULTS: Here we demonstrate that Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation. Moreover, Kaiso regulates several components of the Notch signaling pathway in intestinal cells, namely, Dll-1, Jagged-1 and Notch1. Notably, we found that in Kaiso Tg mice intestines, Notch1 and Dll-1 expression are significantly reduced while Jagged-1 expression is increased. Chromatin immunoprecipitation experiments revealed that Kaiso associates with the DLL1 and JAG1 promoter regions in a methylation-dependent manner in colon carcinoma cell lines, suggesting that these Notch ligands are putative Kaiso target genes. CONCLUSION: Here, we provide evidence that Kaiso's effects on intestinal secretory cell fates precede the development of intestinal inflammation in Kaiso Tg mice. We also demonstrate that Kaiso inhibits the expression of Dll-1, which likely contributes to the secretory cell phenotype observed in our transgenic mice. In contrast, Kaiso promotes Jagged-1 expression, which may have implications in Notch-mediated colon cancer progression.

Patterns of HIV infection among native and refugee Afghans.

The current study was conducted to explore the origins of the HIV epidemics among the Afghan refugees in Pakistan and the native Afghans in Afghanistan. Phylogenetic analysis of HIV gag gene from 40 samples showed diverse HIV variants, originating from a number of countries. Intermixing of diverse HIV variants among Afghans may give rise to seeding of infections with rare HIV strains which may pose serious challenges for the treatment and control of infection.

Communicable disease among displaced Afghans: refuge without shelter.

More than 23 years of warfare in Afghanistan has caused over 6 million Afghans to seek asylum in approximately 70 different countries, with most Afghan refugees settling in the developing countries of Pakistan and Iran. In a developing host country, poor sanitation and nutrition, overcrowding and inaccessibility to health care facilities act synergistically to influence morbidity and mortality from infectious disease in the refugee population. In this Science and Society article we discuss the prevalence of transmissible infection, modes of transmission, associated risk factors, and the state of health and health care in the displaced Afghan population.