Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (α) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&E-stained slides only (H&E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (α = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (α = 0.78, 95% CI = 0.73-0.83) than for H&E-PRGS (α = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (α = 0.61, 95% CI = 0.54-0.68) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (α = 0.66, 95% CI = 0.57-0.75) and moderate for H&E-PRGS (α = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters.

Maximal strength training-induced improvements in forearm work efficiency are associated with reduced blood flow.

Maximal strength training (MST) improves work efficiency. However, since blood flow is greatly dictated by muscle contractions in arms during exercise and vascular conductance is lower, it has been indicated that arms rely more upon adapting oxygen extraction than legs in response to the enhanced work efficiency. Thus, to investigate if metabolic and vascular responses are arm specific, we used Doppler-ultrasound and a catheter placed in the subclavian vein to measure blood flow and the arteriovenous oxygen difference during steady-state work in seven young men [24 ± 3 (SD) yr] following 6 wk of handgrip MST. As expected, MST improved maximal strength (49 ± 9 to 62 ± 10 kg) and the rate of force development (923 ± 224 to 1,086 ± 238 N/s), resulting in a reduced submaximal oxygen uptake (30 ± 9 to 24 ± 10 ml/min) and concomitantly increased work efficiency (9.3 ± 2.5 to 12.4 ± 3.9%) (all P < 0.05). In turn, the work efficiency improvement was associated with reduced blood flow (486 ± 102 to 395 ± 114 ml/min), mediated by a lower blood velocity (43 ± 8 to 32 ± 6 cm/s) (all P < 0.05). Conduit artery diameter and the arteriovenous oxygen difference remained unaltered. The maximal work test revealed an increased time to exhaustion (949 ± 239 to 1,102 ± 292 s) and maximal work rate (both P < 0.05) but no change in peak oxygen uptake. In conclusion, despite prior indications of metabolic and vascular limb-specific differences, these results reveal that improved work efficiency after small muscle mass strength training in the upper extremities is accompanied by a blood flow reduction and coheres with what has been documented for lower extremities. NEW & NOTEWORTHY Maximal strength training increases skeletal muscle work efficiency. Oxygen extraction has been indicated to be the adapting component with this increased work efficiency in arms. However, we document that decreased blood flow, achieved by blood velocity reduction, is the adapting mechanism responding to the improved aerobic metabolism in the forearm musculature.