Notes

[Whipple's illness as well as undoable pulmonary hypertension].
The "macrotrabecular-massive" (MTM) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype and is associated with specific molecular features. Since the immune microenvironment is heterogenous in HCC, it is important to evaluate the immune microenvironment of this novel variant. CMTM6, a key regulator of PD-L1, is an important immunocheckpoint inhibitor. Pelabresib in vivo This study aimed to evaluate the prognostic effect of CMTM6/PD-L1 coexpression and its relationship with inflammatory cells in HCC. We analyzed 619 HCC patients and tumors were classified into MTM and non-MTM HCC subtypes. The expression levels of CMTM6 and PD-L1 in tumor and inflammatory cells were evaluated by immunohistochemistry. The density of inflammatory cells in the cancer cell nest was calculated. Tumoral PD-L1 expression and inflammatory cell density were higher in the MTM type than in the non-MTM type. CMTM6-high expression was significantly associated with shorter OS and DFS than CMTM6-low expression in the whole HCC patient population and the MTM HCC patient population. Moreover, MTM HCC patients with CMTM6/PD-L1 coexpression experienced a higher risk of HCC progression and death. In addition, CMTM6/PD-L1 coexpression was shown to be related to a high density of inflammatory cells. Notably, a new immune classification, based on CMTM6/PD-L1 coexpression and inflammatory cells, successfully stratified OS and DFS in MTM HCC. CMTM6/PD-L1 coexpression has an adverse effect on the prognosis of HCC patients, especially MTM HCC patients. Our study provides evidence for the combination of immune status assessment with anti-CMTM6 and anti-PD-L1 therapy in MTM HCC patients.Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma that has remained a challenge for oncologic and reconstructive surgeons due to a high rate of local recurrence. The objective of this study is to investigate the oncologic and reconstructive benefits of employing a multidisciplinary two-step approach to the treatment of DFSP. A retrospective review was conducted using a prospectively collected database of all patients who underwent resection and reconstruction of large DFSPs by a multidisciplinary team, including a Mohs micrographic surgeon, surgical oncologist, dermatopathologist, and plastic and reconstructive surgeon, at one academic institution from 1998-2018. Each patient underwent Mohs micrographic surgery for peripheral margin clearance (Step 1) followed by wide local excision (WLE) of the deep margin by surgical oncology and immediate reconstruction by plastic surgery (Step 2). 57 patients met inclusion criteria. Average defect size after WLE (Step 2) 87.3 cm2 (range 8.5-1073.5 cm2). Mean follow-up time was 37 months (range 0-138 months). There were no cases of recurrence. A two-step multidisciplinary surgical treatment approach for DFSP minimizes risk of recurrence, decreases patient discomfort, and allows immediate reconstruction after deep margin clearance.
Atypical dopamine (DA) transport blockers such as modafinil and its analogs may be useful for treating motivational symptoms of depression and other disorders. Previous research has shown that the DA depleting agent tetrabenazine can reliably induce motivational deficits in rats, as evidenced by a shift towards a low-effort bias in effort-based choice tasks. This is consistent with human studies showing that people with major depression show a bias towards low-effort activities.

Recent studies demonstrated that the atypical DA transport (DAT) inhibitor (S)-CE-123 reversed tetrabenazine-induced motivational deficits, increased progressive ratio (PROG) lever pressing, and increased extracellular DA in the nucleus accumbens. In the present studies, a recently synthesized modafinil analog, (S, S)-CE-158, was assessed in a series of neurochemical and behavioral studies in rats.

(S, S)-CE-158 demonstrated the ability to reverse the effort-related effects of tetrabenazine and increase selection of high-effort ctions in humans.Despite the possible benefit from avoiding stone surgery with all its possible complications, oral chemolysis is rarely performed in patients with urinary stones suspected of uric acid content. Among the reasons for its limited use is the sparse and low-quality data on its efficacy and the lack of reliable factors predicting its outcome. We thus performed a retrospective single-center cohort study of 216 patients (median patient age 63 years) with 272 renal (48%) and/or ureteral (52%) stones treated with oral chemolysis from 01/2010 to 12/2019. Patients with low urine pH ( less then  6), low stone density upon non-contrast enhanced computed tomography (NCCT), radiolucent urinary stones on plain radiography, and/or a history of uric acid urolithiasis were included. Potassium citrate and/or sodium/magnesium bicarbonate were used for alkalization (target urine pH 6.5-7.2). Median stone size was 9 mm, median stone density 430 Hounsfield Units. Patients with ureteral stones  less then  6 mm were excluded since stones this small are very likely to pass spontaneously. The stone-free status of each patient was evaluated after 3 months using NCCT. Oral chemolysis was effective with a complete and partial response rate of stones at 3 months of 61% and 14%, respectively; 25% of stones could not be dissolved. Lower stone density (OR = 0.997 [CI 0.994-0.999]; p = 0.008) and smaller stone size (OR = 0.959 [CI 0.924-0.995]; p = 0.025) significantly increased the success rate of oral chemolysis in multivariate logistic regression analysis. More precise stone diagnostics to exclude non-uric-acid stones could further improve outcome.
Hypogonadism is a well-established consequence of opioid use. It has been reported in both men and women, although more widely studied in men.

PubMed was searched for articles in English until December 2019 for opioids and hypogonadism. Bibliography of retrieved articles was searched for relevant articles.

The prevalence of opioid-induced hypogonadism (OIH) varies between studies but was reported to be 69% in a recent systematic review. There is large heterogeneity in the studies, with different factors shown to have stronger association with hypogonadism such as specific types of opioids, higher doses, and longer durations of use. The consequences of OIH include sexual dysfunction, depression, decreased quality of life, and low bone density. There is paucity of randomized controlled trials assessing the efficacy of testosterone replacement therapy (TRT) for OIH in men, and even less studies on treating OIH in women. TRT studies in men reported varying outcomes with some studies favoring and others showing no clear benefit of TRT on different measures.
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