Colorectal cancer (CRC) is a complex disease as shown by consensus classification. The present study attempted to identify subtypes with known prognostic markers for better clinical management. A total of 72 CRC tumors were examined for the expression of mismatch repair (MMR) proteins, along with caudal-type homeobox protein 2 (CDX2) and BRCA1, by immunohistochemistry. Tumors were assigned based on the presence or loss of MMR proteins as proficient or deficient. Correlations were examined with CDX2 and BRCA1 along with clinico-pathological features. Expressional pattern of microRNAs (miRs/miRNAs), such as miR-183-96-182, known to be associated with defective DNA damage repair were evaluated by reverse transcription-quantitative PCR. A total of 22% of the CRC tumors were assigned as deficient in mismatch repair. 71% of the tumors expressed CDX2 while only 21% had nuclear expression of BRCA1. Loss of CDX2 protein was higher in the deficient subtype compared with the proficient subtype. A total of 14% of the tumors had dual loss of MMR and BRCA1 proteins and showed aggressive clinical features in addition to elevated expression of DNA damage repair microRNAs. The present study shows the presence of a small proportion of colorectal tumors with dual loss of key proteins involved in DNA damage repair which may be amenable to specific therapy. The implication of the present observations warrants investigation in a larger patient cohort with prognostic information.
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Conclusions:In 2017 Hurricanes Irma and Maria caused major damage to Puerto Rico and had a dramatic impact on dialysis patients. There were high rates of migration off island, missed dialysis treatments and increased deaths. The magnitude is much greater than reports of hurricanes affecting the continental 50 U.S. states. Because most facilities were functional in a few days (16 of 17; 1 was severely damaged), the increase in missed treatments (and reduced treatment time) were likely due to hurricane impact on families and communities; loss of electricity, road closures, safety concerns. Increased deaths were likely due to the same, as well as limited access to food, health care, and potable water. Lessons learned may inform preparedness for future major hurricanes globally.
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