Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Background and Aims

Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies.

Methods

We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI).

Results

Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p = .0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p = .0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p < .0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p < .0001) as predictors of prolonged PPS versus no anticancer therapy.

Conclusions

ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.     

Four-factor prothrombin complex concentrate use for on-label versus off-label indications: a retrospective cohort study

Journal of Thrombosis and Thrombolysis - This study aimed to characterize the utilization of four-factor prothrombin complex concentrate (4F-PCC) at a tertiary academic medical center and evaluate...     

Treatments against Polymorphosal discrepancies in Glioblastoma Multiforme

Glioblastoma (GB) are aggressive tumors that obstruct normal brain function. While the skull cannot expand in response to cancer growth, the growing pressure in the brain is generally the first sign. It can produce more frequent headaches, unexplained nausea or vomiting, blurred peripheral vision, double vision, a loss of feeling or movement in an arm or leg, and difficulty speaking and concentrating; all depend on the tumor’s location. GB can also cause vascular thrombi, damaging endothelial cells and leading to red blood cell leakage. Latest studies have revealed the role of single nucleotide polymorphisms (SNPs) in developing and spreading cancers such as GB and breast cancer. Many discovered SNPs are associated with GB, particularly in great abundance in the promoter region, creating polygenetic vulnerability to glioma. This study aims to compile a list of some of the most frequent and significant SNPs implicated with GB formation and proliferation.

     

A stepped approach for prediction of obstructive sleep apnea in overtly asymptomatic obese subjects: a hospital based study

BACKGROUND AND PURPOSE: Prevalence of obstructive sleep apnea (OSA) is high in obese subjects, many of whom may not be overtly symptomatic. Polysomnography (PSG) is a costly and time-consuming investigation. Since it is not feasible to subject all obese individuals to PSG, it is useful to define predictors of OSA among these subjects. PATIENTS AND METHODS: One hundred and eighteen obese subjects [body mass index (BMI)> or =25 kg/m(2)] presenting to the hospital with non-sleep related complaints were included, of which 53 subjects with PSG evidence of OSA [apnea-hypopnea index (AHI)> or =15/h] were defined as cases and 65 subjects without any evidence of OSA (AHI<15/h) were defined as controls. Anthropometry, biochemical investigations, blood gas analysis, pulmonary function tests, and PSG were performed for all subjects. RESULTS: Waist hip ratio (WHR) (as percentage of a standard) [odds ratio (95% CI): 1.07 (1.00-1.14); P = 0.049] male gender [odds ratio (95% CI): 3.97 (0.99-15.81); P = 0.046] and neck circumference (NC) [odds ratio (95% CI): 1.23 (1.03-1.47); P = 0.023] were found to be independent predictors of OSA. Overnight oxygen desaturation data were evaluated in patients selected as having OSA on the basis of these clinical markers, and the best cut-off for level of desaturation (10%) was defined. The stepped approach had a specificity, sensitivity, positive and negative predictive value of 89.2, 88.5, 86.8 and 90.6%, respectively, for the diagnosis of OSA. CONCLUSIONS: Male gender, WHR and NC are independent predictors of OSA in overtly asymptomatic obese subjects. A stepped approach to diagnose OSA should be used, as it is accurate and cost-effective.     

'Dhat' syndrome--a useful clinical entity

48 consecutive male patients of potency disorders were examined and classified as 'Dhat' syndrome, impotence or premature ejaculation. The age range of these cases was found as 20-38 years (mean 23.5 +/- 3.3 years) while age of onset was 16-24 years (mean 20.6 +/- 4.5 years). Majority of cases were unmarried (54.2%) and educated 5th class or above (79.1%). 31 cases (64.6%) had Dhat syndrome with or without impotency and/or premature ejaculation while 7 cases (14.6%) had only premature ejaculation and 10 cases (20.8%) only impotence. The cases with 'Dhat' syndrome or with impotence scored maximally on neuroticism and depression scales. Neurotic depression was the commonest associated psychiatric illness (39.5%) followed by anxiety neurosis (20.8%) while 31.3% did not have any possible diagnosis. The common presenting symptoms of 'Dhat' syndrome include weakness (70.8%), fatigue (68.7%), palpitations (68.7%), sleeplessness (62.4%) etc. Among the four groups on the basis of type of treatment (antianxiety drug, antidepressant, placebo, psychotherapy), the best response was seen in those receiving antianxiety or antidepressant drugs while those receiving psychotherapy showed minimal response. 7 cases (14.6%) dropped out of treatment and the maximum dropout (40.6%) was seen in psychotherapy group.     

Clinical and epidemiological observations of cutaneous tuberculosis in Larkana,Pakistan

BACKGROUND: Cutaneous tuberculosis is widespread in Pakistan but has not been fully documented. This study was conducted to determine the clinical pattern, nature and existence of the disease in Larkana, Sindh province, Pakistan. METHODS: We are reporting 153 cases of patients with cutaneous tuberculosis who visited our department from 1996 to 1999. All cases were diagnosed at the clinic, and the biopsies were examined for histopathological evidence. The patients received three antituberculous treatments during a 9 month course. RESULTS: Clinically, 63 (41.2%) cases of lupus vulgaris, 54 (35.3%) of scrofuloderma, 29 (19.59%) of lupus verrucosa cutis, six (3.92%) of tuberculosis cutis orificialis and one (0.64%) case of disseminated cutaneous tuberculosis were observed in our department from 1996 to 1999. All patients were aged between 3 and 50 years and had experienced the present complaints for 1 to 12 years. Sixty-nine (45.1%) cases were children aged under 10 years, 50 cases (37.25%) were aged between 10 and 20 years, and 27 cases (17.65%) were aged over 20 years. There was no considerable ratio difference of the disease between male and female patients. Histopathologically, all the specimens showed chronic granulomatous changes; the majority was infiltrated with epitheloid cells, langhans giant cells, plasma cells and other inflammatory cells, such as lymphocytes, eosinophils and neutrophils in ulcerated lesions. Increased numbers of mast cells were seen in upper and lower dermis in two-thirds of the specimens. Caseating necrosis was visible in half of the specimens while Ziehl-Neelsen stain was negative in all the sections. CONCLUSIONS: The observed number of patients was moderately large, thus indicating a high incidence of cutaneous tuberculosis in Larkana. Lupus vulgaris, a form of cutaneous tuberculosis, was widespread in this area and prevalent in adults, while scrofuloderma was prevalent in children. Moreover, the existing rate of the disease was higher in children aged under 10 years and lower in adults. This indicates that children are more prone to this disease than adults.     

Sezary syndrome--without erythroderma

Sezary syndrome (SS), is described as the classical triad of pruritic erythroderma, lymphadenopathy, and presence of more than 10% of circulating Sezary cells in the peripheral blood. We report on unusual case of advanced cutaneous T - cell lymphoma with classical haematological and histopathological features of Sezary syndrome, but lacking the clinical features of erythroderma. A 66 year old man presented with asymptomatic multiple papules, plaques and nodules and with generalized lymphadenopathy. Peripheral smear showed more than 60% of Sezary cells. Skin and lymph node biopsy showed typical features of T-cell lymphoma and immunohistochemistry and CD marker studies showed the cells to be atypical T-lymphocytes. This unusual case is highlighted to denote that erythroderma need not be taken as a hard and fast criterion for diagnosing Sezary syndrome.     

Methicillin-resistant Staphylococcus aureus infection with intermediate sensitivity to vancomycin: a case report and literature review

Staphylococcus aureus is a major cause of bacteremia and endocarditis in adults. Vancomycin is the standard therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Although clinical failure associated with the development of reduced susceptibility to vancomycin during the course of treatment for MRSA bacteremia has been reported infrequently, such an occurrence is very serious. We report a case of 43-year-old woman with of MRSA bacteremia, who relapsed after initial, apparently successful vancomycin treatment and developed left-sided endocarditis and vertebral osteomyelitis. Two weeks into her second admission, the vancomycin minimal inhibitory concentration rose from 相似文献