Benign prostatic hyperplasia (BPH) occurs progressively with aging in men and drives deteriorating symptoms collectively known as lower urinary tract symptoms (LUTS). Age‐associated changes in circulating steroid hormones, and prostate inflammation have been postulated in the etiology of BPH/LUTS. The link between hormones and inflammation in the development of BPH/LUTS is conflicting because they may occur independently or as sequential steps in disease pathogenesis. This study aimed to decipher the prostatic immune landscape in a mouse model of lower urinary tract dysfunction (LUTD). Steroid hormone imbalance was generated by the surgical implantation of testosterone (T) and estradiol (E2) pellets into male C57BL/6J mice and gene expression analysis was performed on ventral prostates (VPs). These experiments identified an increase in the expression of macrophage markers and Spp1/osteopontin (OPN). Localization studies of OPN pinpointed that OPN⁺ macrophages travel to the prostate lumen and transition into lipid‐accumulating foam cells. We also observed a significant increase in the number of tissue macrophages in the VP which was prevented in OPN‐knockout (OPN‐KO) mice. In contrast, mast cells, but not macrophages, were significantly elevated in the dorsal prostate of T + E2‐treated mice which was diminished in OPN‐KO mice. Steroid hormone implantation progressively increased urinary frequency, which was ameliorated in OPN‐KO mice. Our study underscores the role of age‐associated steroid hormone imbalances as a mechanism of expanding the prostatic macrophage population, their luminal translocation, and foam cell differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Fibrogenic and inflammatory processes in the prostate are linked to the development of lower urinary tract symptoms (LUTS) in men. Our previous studies identified that osteopontin (OPN), a pro-fibrotic cytokine, is abundant in the prostate of men with LUTS, and its secretion is stimulated by inflammatory cytokines potentially to drive fibrosis. This study investigates whether the lack of OPN ameliorates inflammation and fibrosis in the mouse prostate. We instilled uropathogenic E. coli (UTI89) or saline (control) transurethrally to C57BL/6J (WT) or Spp1^tm1Blh/J (OPN-KO) mice and collected the prostates one or 8 weeks later. We found that OPN mRNA and protein expression were significantly induced by E. coli-instillation in the dorsal prostate (DP) after one week in WT mice. Deficiency in OPN expression led to decreased inflammation and fibrosis and the prevention of urinary dysfunction after 8 weeks. RNAseq analysis identified that E. coli-instilled WT mice expressed increased levels of inflammatory and fibrotic marker RNAs compared to OPN-KO mice including Col3a1, Dpt, Lum and Mmp3 which were confirmed by RNAscope. Our results indicate that OPN is induced by inflammation and prolongs the inflammatory state; genetic blockade of OPN accelerates recovery after inflammation, including a resolution of prostate fibrosis.

Purpose The purpose of this study was to compare the effects of 3 meal replacement beverages on glycemic response among people with type 2 diabetes. Methods The study examined Glucerna® Weight Loss Shake, Slim-Fast® Shake, and Ensure® with Fiber Shake, using a prospective, 3-way, cross-over design. Eighteen subjects with type 2 diabetes drank the beverages in random order on different weeks. The volume of each beverage was adjusted to include 50 grams of carbohydrates. Glucose was measured 0 to 180 minutes postprandial. Analyses included 2-factor analysis of variance (ANOVA) for repeated measures on both factors, calculation of area under the curve (AUC), and 1-way repeated measures ANOVA of AUC. Results The postprandial glucose profiles of the shakes differed. Glucerna® had the best profile as indicated by the graph of mean postprandial glucose levels and its lower incremental AUC. Despite the superiority of Glucerna®, 2-hour postprandial blood glucose values exceeded the ADA’s recommended upper limit for 22% of the subjects. Conclusions Meal replacement beverages are a popular and potentially effective option for people trying to lose or maintain weight; however, it is unknown to what degrees they affect postprandial blood glucose in people with type 2 diabetes. Because postprandial glycemic excursion is linked to cardiovascular disease, identifying a meal replacement beverage with the lowest glycemic response may mitigate some of the risks in patients with diabetes. Of the meal replacements observed in this study, Glucerna® had the smallest effect on postprandial glucose. Glycemic response to meal replacements should be monitored given product and individual variability.

Background. Kidney transplant recipients (KTRs) are a vulnerable immunocompromised population at risk of severe COVID-19 disease and mortality after SARS-CoV-2 infection. We sought to characterize the post-infection sequelae in KTRs at our center. Methods. We studied all adult KTRs (with a functioning allograft) who had their first episode of SARS-CoV-2 infection between 04/2020 and 04/2022. Outcomes of interest included risk factors for hospitalization, all-cause mortality, COVID-19-related mortality, and allograft failure. Results. Of 979 KTRs with SARS-CoV-2 infection, 381 (39) were hospitalized. In the multivariate analysis, risk factors for hospitalization included advanced age/year (HR: 1.03, 95 CI: 1.021.04), male sex (HR: 1.29, 95 CI: 1.041.60), non-white race (HR: 1.48, 95 CI: 1.171.88), and diabetes as a cause of ESKD (HR: 1.77, 95 CI: 1.412.21). SARS-CoV-2 Vaccination was associated with decreased risk of hospitalization (HR: 0.73, 95 CI: 0.590.90), all-cause mortality (HR: 0.52, 95 CI: 0.370.74), and COVID-19-related mortality (HR: 0.47, 95 CI: 0.310.71) in the univariate and multivariate analyses. Risk factors for both all-cause and COVID-19-related mortality in the multivariate analyses included advanced age, hospitalization, and respiratory symptoms for hospital admission. Furthermore, additional risk factors for all-cause mortality in the multivariate analysis included being a non-white recipient and diabetes as a cause of ESKD, with being a recipient of a living donor as protective. Conclusions. Hospitalization due to COVID-19-associated symptoms is associated with increased mortality. Vaccination is a protective factor against hospitalization and mortality.

This report describes the clinical and histological characteristics and management of a keratinized lesion of the palpebral conjunctiva in a 59-year-old male. The lesion was identified as a rare acantholytic variant of squamous cell carcinoma that atypically arose from a non-sun exposed region of palpebral conjunctiva. Management was complete excision via Mohs surgery. A 59-year-old male presented with ocular irritation and chronic foreign body sensation in the right eye. Exam revealed a keratinized lesion in the right lower tarsal conjunctiva, and an initial shave biopsy was non-diagnostic. 12 months later, the patient presented with similar symptoms and a larger, more irregular lesion for which histopathology of a tarsal-involving excisional biopsy was consistent with acantholytic squamous cell carcinoma with involved margins. The patient subsequently underwent complete excision via Mohs surgery and a secondary reconstruction. Acantholytic variants of squamous cell carcinoma are rare and are described as arising from areas with routine sun exposure. This case reports such a lesion arising from non-sun exposed tarsal conjunctiva, as identified by histopathology of a full-thickness excisional biopsy. The lesion was successfully managed with complete excision via Mohs surgery and secondary reconstruction. Given that this histologic variant may be more aggressive and have higher rates of recurrence than other forms of squamous cell carcinoma, this case highlights the importance of complete excisional biopsy and accurate histopathology of concerning periocular lesions and offers a template for management of similar lesions. The unique presenting location should bring awareness to consideration of this type of malignancy developing on palpebral conjunctiva.