Dosimetric impact on changes in target volumes during intensity-modulated radiotherapy for nasopharyngeal carcinoma

Background and purposeTo assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact.Patients and methodsTwenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated.ResultsWe observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01).ConclusionTumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients.     

Mixed-beam approach for high-risk prostate cancer: Carbon-ion boost followed by photon intensity-modulated radiotherapy. Dosimetric and geometric evaluations (AIRC IG-14300)

Background and purposeThe aim was to evaluate dosimetric uncertainties of a mixed beam approach for patients with high-risk prostate cancer (PCa). The treatment consists of a carbon ion radiotherapy (CIRT) boost followed by whole-pelvis intensity-modulated RT (IMRT).Materials and methodsPatients were treated with a CIRT boost of 16.6 Gy/4 fractions followed by whole-pelvis IMRT of 50 Gy/25 fractions, with consequent long term androgen deprivation therapy. Deformable computed tomography image registration (DIR) was performed and corresponding doses were used for plan sum. A comparative IMRT photon plan was obtained as whole-pelvis IMRT of 50 Gy/25 fractions followed by a boost of 28 Gy/14 fractions. DIR performances were evaluated through structure-related and image characteristics parameters.ResultsUntil now, five patients out of ten total enrolled ended the treatment. Dosimetric parameters were lower in CIRT + IMRT than IMRT-only plans for all organs at risk (OARs) except femoral heads.Regarding DIR evaluation, femoral heads were the less deformed OAR. Penile bulb, bladder and anal canal showed intermediate deformation. Rectum was the most deformed. DIR algorithms were patient (P)-dependent, as performances were the highest for P3 and P4, intermediate for P2 and P5, and the lowest for P1.ConclusionsCIRT allows better OARs sparing while increasing the efficacy due to the higher radio-biological effect of carbon ions. However, a mixed beam approach could introduce DIR problems in multi-centric treatments with different operative protocols. The development of this prospective trial will lead to more mature data concerning the clinical impact of implementing DIR procedures in dose accumulation applications for high-risk PCa treatments.     

The effect of radiation therapy on post-prostatectomy urinary function

AimWe sought to evaluate the effect of radiation therapy on post-prostatectomy urinary quality of life in prostate cancer patients.BackgroundIn some men with non-metastatic prostate cancer, radiation therapy is indicated following prostatectomy. The radiation toxicity and quality of life considerations are unique in the post-prostatectomy setting.Materials and methodsA total of 106 patients receiving post-prostatectomy radiation therapy completed the Expanded Prostate Cancer Index Composite questionnaire before radiation and at 2-year follow-up. The primary outcomes of this study were the urinary domain summary score and subscale scores. Planned analysis was performed based on time interval from prostatectomy to radiation therapy.ResultsAmong the 106 patients analyzed, the mean urinary domain summary score worsened at 2-year follow-up after radiation therapy, lowering from 77.23–72.51 (p = 0.0085). Similar worsening was observed in the subscales of function (p = 0.003), bother (p = 0.0397), and incontinence (p = 0.0003). Urinary incontinence showed the greatest observable change among subscales. While the summary score worsened (p = 0.0031) among patients receiving radiation therapy more than 1 year after prostatectomy, it did not show statistically significant change in those treated 1 year or less after prostatectomy.ConclusionOur results demonstrate that post-prostatectomy radiation therapy is associated with modest declines in reportable urinary quality of life. Patients receiving radiation therapy more than 1 year after prostatectomy showed greater worsening of urinary quality of life, which indicates that there may be no functional advantage to delaying radiation therapy beyond the initial postoperative period.     

Total skin electron beam therapy for primary cutaneous T-cell lymphomas: clinical characteristics and outcomes in a Mexican reference center

AimThe aim of this study was to assess treatment modalities, treatment response, toxicity profile, disease progression and outcomes in 14 patients with a confirmed diagnosis of primary cutaneous T-cell lymphoma (PCTCL) treated with total skin electron beam therapy (TSEBT).BackgroundPrimary cutaneous lymphomas (PCLs) are extranodal non-Hodgkin lymphomas originating in the skin without evidence of extracutaneous disease at diagnosis. Despite advances in systemic and local therapy options, the management of advanced stages remains mostly palliative.Materials and MethodsThis is a retrospective study of patients with PCTCL, diagnosed and treated in a reference center in Mexico City, analyzing treatment modalities, response to treatment, long-term outcome, and mortality.ResultsEight males (57%) and 6 (43%) females were identified. Most patients were stage IVA (n = 5, 36%) followed by stage IB and IIB (28.5% and 21.4%, respectively). Eleven patients received the low-dose RT scheme (12 Gy), 1 patient, the intermediate-dose RT scheme (24 Gy), and 2 patients, the conventional-dose RT scheme (36 Gy). Mean follow-up time was 4.6 years. At first follow-up examination, 6–8 weeks after radiotherapy, the overall response rate (ORR) for the cohort was 85%. The median PFS for the whole cohort was 6 months.ConclusionThis study reinforces the role of TSEBT when compared with other treatment modalities and novel agents. Low-dose TSEBT is now widely used because of the opportunity for retreatment.     

American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions

ObjectiveThe objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes.MethodsA literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review.ResultsMinimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer.ConclusionSurgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.     

Weight-Based Insulin During and After Intravenous Insulin Infusion Reduces Rates of Rebound Hyperglycemia When Transitioning to Subcutaneous Insulin in the Medical Intensive Care Unit

ObjectiveHyperglycemia often occurs after the transition from intravenous insulin infusion (IVII) to subcutaneous insulin. Weight-based basal insulin initiated earlier in the course of IVII in the medical intensive care unit (MICU), and a weight-based basal-bolus regimen after IVII, can potentially improve post-IVII glycemic control by 48 hours.MethodsThis prospective study included 69 patients in MICU who were on IVII for ≥24 hours. Exclusions were end-stage renal disease, type 1 diabetes mellitus, and the active use of vasopressors. The intervention group received weight-based basal insulin (0.2-0.25 units/kg) with IVII and weight-based bolus insulin after IVII. The control group received current care. The primary end points were glucose levels at specific time intervals up to 48 hours after IVII.ResultsThere were 25 patients in the intervention group and 44 in the control group. The mean age of the patients was 59 ± 15 years, 32 (47%) were men, and 52 (78%) had prior diabetes mellitus. The 2 groups were not different (acute kidney injury/chronic kidney disease, pre-existing diabetes mellitus, illness severity, or nothing by mouth status after IVII), except for the steroid use, which was higher in the control group than in the intervention group (34% vs 12%, respectively). Glucose levels were not lower until 36 to 48 hours after IVII (166.8 ± 39.1 mg/dL vs 220.0 ± 82.9 mg/dL, P < .001). When controlling for body mass index, nutritional status, hemoglobin A1C, and steroid use, glucose level was lower starting at 12 to 24 hours out (166.87 mg/dL vs 207.50 mg/dL, P = .015). The frequency of hypoglycemia was similar between the 2 groups (5.0% vs 7.1%). The study did not reach target enrollment.ConclusionThe addition of weight-based basal insulin during, and basal-bolus insulin immediately after, IVII in MICU results in better glycemic control at 24 hours after IVII with no increased hypoglycemia.     

l-carnitine: Nutrition,pathology, and health benefits

Carnitine is a medically needful nutrient that contributes in the production of energy and the metabolism of fatty acids. Bioavailability is higher in vegetarians than in people who eat meat. Deficits in carnitine transporters occur as a result of genetic mutations or in combination with other illnesses such like hepatic or renal disease. Carnitine deficit can arise in diseases such endocrine maladies, cardiomyopathy, diabetes, malnutrition, aging, sepsis, and cirrhosis due to abnormalities in carnitine regulation. The exogenously provided molecule is obviously useful in people with primary carnitine deficits, which can be life-threatening, and also some secondary deficiencies, including such organic acidurias: by eradicating hypotonia, muscle weakness, motor skills, and wasting are all improved l-carnitine (LC) have reported to improve myocardial functionality and metabolism in ischemic heart disease patients, as well as athletic performance in individuals with angina pectoris. Furthermore, although some intriguing data indicates that LC could be useful in a variety of conditions, including carnitine deficiency caused by long-term total parenteral supplementation or chronic hemodialysis, hyperlipidemias, and the prevention of anthracyclines and valproate-induced toxicity, such findings must be viewed with caution.     

KCNJ5 Mutation Contributes to Complete Clinical Success in Aldosterone-Producing Adenoma: A Study From a Single Center

ObjectiveThe KCNJ5 mutation is the most frequent mutation in aldosterone-producing adenoma (APA). We aimed to illustrate the relationship between KCNJ5 and prognosis after adrenalectomy as a guide for further treatment.MethodsOur study included 458 patients with APA. Tumor tissues were screened for somatic mutations in KCNJ5 hot-spot regions. We performed a retrospective analysis to identify correlations between KCNJ5 and clinical outcomes in 334 patients with adrenal venous sampling lateralization.ResultsSomatic KCNJ5 mutations were identified in 324 of 458 patients with APA (70.7%). Compared with the KCNJ5-wild type patients, patients with KCNJ5 mutations were younger, had a higher proportion of women, and had shorter durations of hypertension, lower body mass indexes (BMIs), and lower systolic blood pressure values (P < .05). During follow-up, among the 334 patients with APA with adrenal venous sampling lateralization, 320 (95.8%) presented complete biochemical success and 187 (56.0%) presented complete clinical success. One hundred eighty-seven patients with primary aldosteronism who achieved complete clinical success presented the following characteristics: age <40 years (78.7%), BMI <24 kg/m² (71.0%), hypertension duration <5 years (78.4%), females (66.9%), and KCNJ5 mutation (65.5%). A multivariate logistic regression analysis identified BMI, hypertension duration, and KCNJ5 mutation as independent predictors of complete clinical success.ConclusionThe prevalence of KCNJ5 mutations was 70.7%. KCNJ5 mutation is a protective factor of complete clinical success, while BMI and hypertension duration were risk factors of incomplete clinical success.     

Lipoprotein(a), family history of cardiovascular disease,and incidence of heart failure

Lipoprotein(a) (Lp(a)) is a largely genetically determined biomarker for cardiovascular disease (CVD), while its potential interplay with family history (FHx) of CVD, a measure of both genetic and environmental exposures, remains unclear. We examined the associations of Lp(a) in terms of circulating concentration or polygenetic risk score (PRS), and FHx of CVD with risk of incident heart failure (HF). Included were 299,158 adults from the UK Biobank without known HF and CVD at baseline. Hazards ratios (HRs) and 95% Cls were estimated by Cox regression models adjusted for traditional risk factors defined by the Atherosclerosis Risk in Communities study HF risk score. During the 11.8-year follow-up, 5,502 incidents of HF occurred. Higher levels of circulating Lp(a), Lp(a) PRS, and positive FHx of CVD were associated with higher risks of HF. Compared with individuals who had lower circulating Lp(a) and no FHx, HRs (95% CIs) of HF were 1.36 (1.25, 1.49), 1.31 (1.19, 1.43), and 1.42 (1.22, 1.67) for those with higher Lp(a) and a positive history of CVD for all family members, parents, and siblings, respectively; similar results were observed by using Lp(a) PRS. The risk estimates for HF associated with elevated Lp(a) and positive FHx were attenuated after excluding those with incident myocardial infarction (MI) during follow-up. Lp(a) and FHx of CVD were independent risk factors for incident HF, and the highest risk of HF was observed among individuals with both risk factors. The association may be partly mediated by myocardial infarction.     

Clinical,Hormonal, and Genetic Characteristics of 5α-Reductase Type 2 Deficiency in 103 Chinese Patients

Objective5α-Reductase type 2 (5α-RD2) deficiency causes variable degrees of undervirilization in patients. The correlation between its genotype and phenotype is unclear.MethodsWe retrospectively evaluated 103 patients with 46,XY disorders of sex development who were diagnosed with 5α-RD2 deficiency.ResultsThe prevalence of female sex assignment (P = .008) and the incidences of cryptorchidism (P = .0003) and bifid scrotum (P = .0002) in the non-p.R227Q variant group were higher, but there were no significant differences in the incidences of hypospadias and isolated microphallus. The external masculinization score in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P = .019) and compound heterozygous p.R227Q variant groups (P = .013). The level of anti-Mullerian hormone in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P < .001) and compound heterozygous p.R227Q variant groups (P = .006). The testosterone-to-dihydrotestosterone ratio of the homozygous p.R227Q variant group was higher than that of the non-p.R227Q variant (P = .018) and compound heterozygous p.R227Q variant groups (P = .029). Twenty-three reportedly pathogenic variants and 11 novel steroid 5α-reductase 2 (SRD5A2) variants were identified.ConclusionCompared with patients without p.R227Q, patients with p.R227Q exhibited higher external masculinization scores and anti-Mullerian hormone expression, a lower prevalence of female sex assignment, and lower incidences of cryptorchidism and bifid scrotum. We identified 23 reportedly pathogenic SRD5A2 variants and 11 novel SRD5A2 variants that led to 5α-RD2 deficiency. We established a genotype-phenotype correlation, and patients with p.R227Q showed a relatively mild phenotype.     

Cholesterol metabolism: from lipidomics to immunology

Oxysterols, the oxidized forms of cholesterol or of its precursors, are formed in the first steps of cholesterol metabolism. Oxysterols have interested chemists, biologists, and physicians for many decades, but their exact biological relevance in vivo, other than as intermediates in bile acid biosynthesis, has long been debated. However, in the first quarter of this century, a role for side-chain oxysterols and their C-7 oxidized metabolites has been convincingly established in the immune system. 25-Hydroxycholesterol has been shown to be synthesized by macrophages in response to the activation of Toll-like receptors and to offer protection against microbial pathogens, whereas 7α,25-dihydroxycholesterol has been shown to act as a chemoattractant to lymphocytes expressing the G protein-coupled receptor Epstein-Barr virus-induced gene 2 and to be important in coordinating the action of B cells, T cells, and dendritic cells in secondary lymphoid tissue. There is a growing body of evidence that not only these two oxysterols but also many of their isomers are of importance to the proper function of the immune system. Here, we review recent findings related to the roles of oxysterols in immunology.     

Subclinical Hyperthyroidism: A Review of the Clinical Literature

Subclinical hyperthyroidism (SCHyper) is a biochemical diagnosis characterized by a decreased serum thyroid-stimulating hormone (TSH) and normal serum thyroxine (T4) and triiodothyronine (T3) concentrations. Because SCHyper can be resolved, it is recommended to repeat serum TSH, T3, and T4 concentrations in 3 to 6 months before confirming a diagnosis of SCHyper to consider treatment. Proposed grading systems distinguish between mild (TSH, 0.1-0.4 mIU/L) and severe SCHyper (TSH, <0.1 mIU/L) and are used alongside patients’ age and the presence of risk factors and symptoms to guide treatment. Appropriate evaluation includes an investigation of the underlying cause and assessment of an individual’s risk factors to determine the necessity and type of treatment that may be recommended. SCHyper may be associated with increased risks of cardiovascular-related adverse outcomes, bone loss, and in some studies, cognitive decline. Treatment may include observation without therapy, initiation of antithyroid medications, or pursuit of radioiodine therapy or thyroid surgery. Considerations for treatment include the SCHyper etiology, anticipated long-term natural history of the condition, potential benefits of correcting the thyroid dysfunction, and risks and benefits of each treatment option. The purpose of this overview is to provide a guide for clinicians in evaluating and managing SCHyper in the routine clinical practice.     

Osilodrostat: A Review of Recent Clinical Studies and Practical Recommendations for its Use in the Treatment of Cushing Disease

ObjectiveCushing disease (CD) is characterized by chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. Surgery remains the first-line treatment option; however, medical therapy is essential if surgery is contraindicated or fails to achieve remission or when recurrence occurs after surgical remission. Osilodrostat (Isturisa), a novel steroidogenic inhibitor, is now approved for the treatment of CD in the United States and Cushing syndrome in Europe. Herein, we review pharmacology and data on the efficacy, safety, and clinical use of osilodrostat and provide guidance on its use in treating patients with CD.MethodsWe reviewed the literature and published clinical trial data of osilodrostat use in patients with Cushing syndrome. Detailed information related to the clinical assessment of osilodrostat use, potential drug-to-drug interactions, drug initiation, dose titration, and the monitoring of drug tolerability were discussed.ResultsClinical trial data demonstrated that osilodrostat, by virtue of inhibiting 11-β hydroxylase, potently and rapidly decreased the 24-hour urinary free cortisol levels and sustained these reductions, with improved glycemia, blood pressure, body weight, and quality of life as well as lessened depression. Osilodrostat may interact with certain drugs, resulting in QT prolongation, which requires careful assessment of concomitant medications and periodic monitoring using electrocardiogram, respectively. The common adverse effects include adrenal insufficiency, hypokalemia, edema, and hyperandrogenic symptoms, which can be minimized using a slower up-titration dosing regimen.ConclusionOsilodrostat is an effective, new treatment option for CD, with positive effects on cardiovascular and quality of life parameters as well as tolerable adverse effects. This article provides a review of the pharmacology of osilodrostat and offers practical recommendations on the use of osilodrostat to treat CD.     

Isopod crustacean fossils from the Cenomanian stratotype: five new species in suborders Cymothoida,Asellota and Valvifera

We report on a significant fossil collection of five isopod crustaceans that belong to five families from three suborders. These fossils were discovered in Le Mans (western part of Paris Basin, France) during the second half of the nineteenth century by the French paleontologist Edouard Guéranger. The historical quarry has been studied a few years before by the French paleontologist Alcide d’Orbigny and used as part of his Cenomanian stratotype (Leach, 1814). The collection consists of two species in the Cymothooidea Dana, 1852 (Cirolanidae Dana, 1852; Lantoceramiidae fam. nov.), two Valvifera G. O. Sars, 1883 (Chaetiliidae Dana, 1853; Idoteidae Samouelle, 1819) and one Asellota Latreille, 1802 (Stenetriidae Hansen, 1905), which were previously unknown from Upper Cretaceous strata as old as the Cenomanian age (roughly 93–99 ma). Although phylogenetic dating based on extant taxa has assigned Permian to Triassic age of origin for the Asellota, the Stenetriidae Hansen, 1905 specimen is the first fossil record for this family. Another asellotan, Fornicaris calligarisi Wilson and Selden, 2016, is known from the Triassic (Norian) dating from approximately 210–215 ma. The valviferans were unknown from Mesozoic strata, previously being found in the Oligocene of Romania and the Fur Formation, Upper Paleocene/Lowermost Eocene of Denmark (Polz, 2007). This diverse assemblage of fossils with taxa assignable to extant families and one new family provides evidence for the presence of a substantially modern isopod fauna as early as the Cenomanian.     

A Novel Spectral Annotation Strategy Streamlines Reporting of Mono-ADP-ribosylated Peptides Derived from Mouse Liver and Spleen in Response to IFN-γ

Mass-spectrometry-enabled ADP-ribosylation workflows are developing rapidly, providing researchers a variety of ADP-ribosylome enrichment strategies and mass spectrometric acquisition options. Despite the growth spurt in upstream technologies, systematic ADP-ribosyl (ADPr) peptide mass spectral annotation methods are lacking. HCD-dependent ADP-ribosylome studies are common, but the resulting MS2 spectra are complex, owing to a mixture of b/y-ions and the m/p-ion peaks representing one or more dissociation events of the ADPr moiety (m-ion) and peptide (p-ion). In particular, p-ions that dissociate further into one or more fragment ions can dominate HCD spectra but are not recognized by standard spectral annotation workflows. As a result, annotation strategies that are solely reliant upon the b/y-ions result in lower spectral scores that in turn reduce the number of reportable ADPr peptides. To improve the confidence of spectral assignments, we implemented an ADPr peptide annotation and scoring strategy. All MS2 spectra are scored for the ADPr m-ions, but once spectra are assigned as an ADPr peptide, they are further annotated and scored for the p-ions. We implemented this novel workflow to ADPr peptides enriched from the liver and spleen isolated from mice post 4 h exposure to systemic IFN-γ. HCD collision energy experiments were first performed on the Orbitrap Fusion Lumos and the Q Exactive, with notable ADPr peptide dissociation properties verified with CID (Lumos). The m-ion and p-ion series score distributions revealed that ADPr peptide dissociation properties vary markedly between instruments and within instrument collision energy settings, with consequences on ADPr peptide reporting and amino acid localization. Consequentially, we increased the number of reportable ADPr peptides by 25% (liver) and 17% (spleen) by validation and the inclusion of lower confidence ADPr peptide spectra. This systematic annotation strategy will streamline future reporting of ADPr peptides that have been sequenced using any HCD/CID-based method.     

Esophageal squamous cell carcinoma and adenocarcinoma in Malaysia – Pooled data from upper gastrointestinal centers in a multiethnic Asian population

BackgroundEsophageal cancer is the sixth leading cause of cancer death worldwide with considerable geographical histological variation There is a paucity of data in esophageal cancer in demographics, histology, and survival among the multi-ethnic Malaysian population. This paper is a review of esophageal cancer epidemiology and survival among esophageal cancer patients from data collected by the Malaysian Upper Gastrointestinal Surgical Society.MethodsThis is a multicenter retrospective observational study of esophageal cancer patients from six upper gastrointestinal surgical centers in Malaysia between 2005 and 2019. Patient characteristics, histological type and stage were compared and survival analyzed.ResultsThere were 820 patients with esophageal cancer included, where 442 (53.9 %) cases had squamous cell carcinoma (SCC) and 378 (46.1 %) had adenocarcinomas (AC). Malays were the predominant ethnicity with AC (66.7 %) while Indians were the ethnic majority (74.6 %) with SCC. Majority of patients (56.8 %) presented as stage IV disease. Overall, the 1-, 3-, and 5-years’ survival were 35.8 %, 13.8 % and 11.0 %, respectively. Surgical resection with curative intent yielded the best 5-year survival (29.4 %). Intervention in stage IV AC yielded superior survival when compared to SCC (median survival, 7.9 months vs 4.8 months; p, 0.018) Our series demonstrated an increase in AC to SCC over the last 15 years.ConclusionsThere was an ethnic preponderance seen between different histology in this region, not previously discussed. An increase in AC was observed over the last 15 years. Late diagnosis seen in most patients imparts poor prognosis as curative surgery affords the best outcome.     

Pancreatoblastoma in children: Clinical management and literature review

PurposeThe aim of this study is to analyze the clinical and pathological features of pancreatoblastoma (PB) and to obtain better management for patients with relapsed or metastatic disease.MethodsFour cases treated in our institution and 59 cases reported previously in the literature from the PubMed biomedical database (2000–2020) were reviewed and analyzed.ResultsFour cases with PB presented with abdominal pain and palpable abdominal masses, with the tumor size ranging from 5.2 to 18 cm in diameter. The invasion of the splenic vein and superior mesenteric artery, duodenum, and lymph nodes were risk factors for PB. Three cases were treated with combination therapy and showed favorable outcomes, while one case was treated with chemotherapy alone due to tumor progression and died of the disease. Squamous corpuscles were revealed in the tumor samples and considered a defining component for histological diagnosis.ConclusionsMultidisciplinary diagnosis plays an important role in clinical management. The risk factors should be considered in the therapeutic stratification of PB before surgery.     

American Association of Clinical Endocrinology Disease State Clinical Review: Evaluation and Management of Immune Checkpoint Inhibitor-Mediated Endocrinopathies: A Practical Case-Based Clinical Approach

ObjectiveThe aim of this case-based clinical review was to provide a practical approach for clinicians regarding the management of patients with immune checkpoint inhibitor (ICI)-mediated endocrinopathies.MethodsA literature search of PubMed, Embase, and Scopus was conducted using appropriate keywords. The discussions and strategies for the diagnosis and management of ICI-mediated endocrinopathies are based on evidence available from prospective, randomized clinical studies; cohort studies; cross-sectional studies; case-based studies; and an expert consensus.ResultsImmunotherapy with ICIs has transformed the treatment landscape of diverse types of cancers but frequently results in immune-mediated endocrinopathies that can cause acute and persistent morbidity and, rarely, death. The patterns of endocrinopathies differ between the inhibitors of the cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 or programmed cell death protein 1 ligand pathways but most often involve the thyroid and pituitary glands. The less common but important presentations include insulin-deficient diabetes mellitus, primary adrenal insufficiency, primary hypoparathyroidism, central diabetes insipidus, primary hypogonadism, and pancreatitis, with or without subsequent progression to diabetes mellitus or exocrine insufficiency.ConclusionIn recent years, with increasing numbers of patients with cancer being treated with ICIs, more clinicians in a variety of specialties have been called upon to diagnose and treat ICI-mediated endocrinopathies. Herein, we reviewed case scenarios of various clinical manifestations and emphasized the need for a high index of clinical suspicion by all clinicians caring for these patients, including endocrinologists, oncologists, primary care providers, and emergency department physicians. We also provided diagnostic and therapeutic approaches for ICI-induced endocrinopathies and proposed that patients on ICI therapy be evaluated and treated by a multidisciplinary team in collaboration with endocrinologists.     

Impact on S. aureus and E. coli Membranes of Treatment with Chlorhexidine and Alcohol Solutions: Insights from Molecular Simulations and Nuclear Magnetic Resonance

Membranes form the first line of defence of bacteria against potentially harmful molecules in the surrounding environment. Understanding the protective properties of these membranes represents an important step towards development of targeted anti-bacterial agents such as sanitizers. Use of propanol, isopropanol and chlorhexidine can significantly decrease the threat imposed by bacteria in the face of growing anti-bacterial resistance via mechanisms that include membrane disruption. Here we have employed molecular dynamics simulations and nuclear magnetic resonance to explore the impact of chlorhexidine and alcohol on the S. aureus cell membrane, as well as the E. coli inner and outer membranes. We identify how sanitizer components partition into these bacterial membranes, and show that chlorhexidine is instrumental in this process.