Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium’s Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response.     

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

Italian Clinical Practice Guidelines on Cholangiocarcinoma – Part II: Treatment

Currently, the only curative treatment for cholangiocarcinoma (CCA) is surgical resection, though this treatment is possible in less than 40% of patients. However, recent improvements in preoperative management have led to a higher number of patients who are candidates for this procedure. For unresectable patients, progress is ongoing in terms of locoregional and chemoradiation treatments and target therapies, especially in the definition of patient selection criteria. This is the second part of the Italian CCA guidelines, dealing with CCA treatment, that have been formulated in accordance with Italian National Institute of Health indications and developed according to the GRADE method and related advancements.     

Risk Factors Associated With New-Onset Diabetes After Liver Transplant: A Case Control Study

BackgroundNew-onset diabetes after transplant is a severe complication that can present in liver transplant recipients, negatively impacting quality of life and graft survival. It also contributes to increased risk of infection, cardiovascular disease, and rejection, which are the main causes of death among liver transplant recipients. The aim of the present study was to assess the risk factors associated with new-onset diabetes after transplant.MethodThis was a case control study based on the data from 146 liver transplant patients at a reference hospital. The data from the charts were collected using a 2-part form: Part I (sociodemographic variables) and Part II (clinical variables).ResultsMultiple analysis showed that pre-existing systemic arterial hypertension (odds ratio [OR], 2.65; 95% CI, 1.12–6.28) and the use of sodium mycophenolate associated with tacrolimus (OR, 2.68; 95% CI, 1.02–7.06) increased the risk of new-onset diabetes after transplant. On comparing the anthropometric variables, lipid panel, and blood glucose levels of liver transplant patients with and without diabetes, higher glycemic levels were found in the group with diabetes (P < .001).ConclusionPre-existing systemic arterial hypertension and the associated use of sodium mycophenolate and tacrolimus increased the risk of new-onset diabetes after transplant.     

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

Dietary and herbal supplements use among patients hospitalized in internal medicine departments

ObjectivesTo assess consumption of dietary and herbal supplements (DHS) among patients in internal medicine departments and determine whether such use is documented in their medical files.Methods267 patients from three internal medicine departments of an academic medical center in Haifa, Israel were assessed prospectively with questionnaires about their DHS use in the month preceding hospitalization. DHS were categorized into vitamins & minerals, herbal supplements and others. Further data was then collected from patients' medical records on socio-demographic and medical characteristics, as well as documentation of DHS use.Results123 patients (50.6 %) used DHS on a daily basis. Most of them (53.7 %) were using more than one DHS. DHS use was more prevalent in older (OR = 1.02 [1.001–1.036], p = 0.034) and educated (OR = 0.482 [0.252-0.923], p = 0.028) patients. Vitamins & minerals were used mainly to enhance vitality and address laboratory abnormalities, whereas herbal supplements were used mainly for gastrointestinal problems (p < 0.001). DHS use was reported to the physicians by 42 % of the patients, mostly at the patients’ initiative [92 (82.1 %), p < 0.001)]. Vitamins and minerals were the most reported category of DHS (94 (57.3 %), p < 0.001). The use of DHS was reported to physicians for 112 DHS (41.8 %) but only 32 DHS (11.9 %) were documented in their medical files. The documentation of vitamins and minerals was significantly higher compared to herbal supplements documentation (29 (17.7 %) & 3 (2.9 %) respectively, P < 0.001).ConclusionsDHS are commonly used by patients hospitalized in the internal medicine departments. Many patients do not report such use to the physicians, and more strikingly, physicians do not document DHS use in patient medical files. This communication gap may have serious medico-legal ramifications due to DHS side effects and DHS interactions with other DHS and with conventional drugs.