Diagnosis of alpha-1-antitrypsin deficiency in bleeding disorder-related neonatal death

Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disorder characterized by hepatitis in neonates, childhood and adulthood (protease inhibitor (PI)*ZZ) and emphysema with or without hepatitis (PI*ZZ)/(PI*SS,SZ or null) in adulthood. We report the case of a female neonate born at 40 weeks of gestation who presented with vitamin K deficiency-related intracranial bleeding and cholestasis of which she died at 28 days of age. At autopsy, the infant was found to have intracranial bleeding, hepatomegaly, and cholestasis with paucity of bile ducts in the liver. Small periodic acid-Schiff diastase positive intrahepatic granules and positive staining with antibodies against AAT protein suggested an AAT deficiency. AAT is a glycoprotein that has a protease inhibitor function. Its deficiency can be the result of various point mutations in Serpin 1 located on chromosome 14. The diagnosis AAT deficiency was confirmed by mutation analysis showing the PI*ZZ genotype in the neonate. In conclusion, AAT deficiency is a rare genetic disorder that can lead to a serious bleeding disorder in the neonatal period if not recognised on time. Pathological diagnosis together with verifying molecular analysis can be used to identify index patients

Intracranial bleeding due to vitamin K deficiency: advantages of using a pediatric intensive care registry

Item does not contain fulltextAIM: To determine the incidence of late intracranial vitamin K deficiency bleeding (VKDB) in The Netherlands using the Dutch Pediatric Intensive Care Evaluation (PICE) registry. METHODS: The PICE registry was used to identify all infants who were admitted to a Dutch pediatric intensive care unit (PICU) with intracranial bleeding between 1 January 2004 and 31 December 2007. Cases of confirmed late intracranial VKDB were used to calculate the incidence for each year. To estimate the completeness of ascertainment of the PICE registry, data from 2005 were compared with general surveillance data from that year. RESULTS: In the 4-year study period, 16/64 (25%) of the infants admitted with intracranial bleeding had late intracranial VKDB, resulting in an overall incidence of 2.1/100,000 live births (95% confidence interval 1.2-3.5). The single-year incidence varied markedly between 0.5 and 3.3 per 100,000 live births. All five ascertained cases in 2005 were identified using the PICE registry, while general surveillance identified only three. CONCLUSIONS: The PICE registry allows ongoing monitoring of the incidence of late intracranial VKDB and appears to be associated with a higher rate of completeness than general surveillance. We propose the use of pediatric intensive care registries to assess the efficacy of national vitamin K prophylactic regimens

Treatment and survival of Merkel cell carcinoma since 1993: A population-based cohort study in The Netherlands

Background: Merkel cell carcinoma (MCC) is a rare and potentially lethal skin cancer. MCC is known for its potential rapid growth and its propensity to metastasize. Objective: To describe the incidence, treatment, and survival of MCC in a population-based setting. Methods: All MCCs diagnosed in The Netherlands between 1993 and 2016 were selected from the Netherlands Cancer Registry. Patient and tumor characteristics, therapy, and vital status were obtained. Cox proportional hazards were computed, and relative survival analyses were performed. Results: Our cohort included 1977 patients with MCC. Incidence increased from 0.17 per 100,000 person-years in 1993 to 0.59 per 100,000 in 2016. The mean age at diagnosis was 75.5. Most MCCs (59.8%) were treated with surgery alone. Relative 5-year survival was low (63.0%) and did not improve. Mortality was higher among males (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.11-1.39), higher age (HR, 1.07; 95% CI, 1.06-1.07), and nodal (HR, 1.26; 95% CI, 1.08-1.48) and distant spread of disease (HR, 2.44; 95% CI, 1.99-2.99). Limitations: We lacked data on cause of death, comorbidity, and pathologic margins, which may have led to misinterpretation of the data. Conclusion: This study shows continuously increasing incidence rates of MCC in The Netherlands. Survival after a diagnosis of MCC remained low. Our results emphasize the need for implementation of new therapies

The role of phototherapy in the surgical treatment of vitiligo: a systematic review

Vitiligo is frequently treated with the combination of phototherapy and melanocyte transplantation. However, the additional benefit of phototherapy is unclear. Moreover, the optimal type and regimen of phototherapy are unknown. The objective of this systematic review was to identify whether phototherapy improves the outcome of melanocyte transplantation in vitiligo. We searched and screened for eligible studies in the databases of MEDLINE, EMBASE and CENTRAL. We included all clinical studies investigating melanocyte transplantation combined with phototherapy. After screening and selection of abstracts and full-texts, we found 39 eligible clinical studies with 1624 patients. The eligible studies investigated several phototherapy modalities, such as NBUVB (n = 9), PUVA (n = 19), UVA (n = 1), MEL (n = 4) and active sunlight exposure (n = 9). Four studies directly compared phototherapy versus no phototherapy and two studies confirmed the benefit of phototherapy for melanocyte transplantation. We found no significant differences in repigmentation in studies directly comparing phototherapy modalities. The overall quality of the studies was moderate to poor and high heterogeneity between studies was found. We found limited evidence that phototherapy improves the outcome of melanocyte transplantation in vitiligo. There is insufficient evidence to recommend a specific type or regimen of phototherapy. More studies should be performed investigating the additional benefit of different phototherapies and the preferred moment of phototherapy

Merkel Cell Carcinoma, the Impact of Clinical Excision Margins and Mohs Micrographic Surgery on Recurrence and Survival: A Systematic Review

BACKGROUND: When treating Merkel cell carcinoma (MCC), the relation between wide local excision (WLE) margin and recurrence or survival is unclear. Mohs micrographic surgery (MMS) is an alternative surgical option for MCC, but it is unknown whether the local recurrence rate differs between MMS and WLE. OBJECTIVE: To systematically assess the available literature to determine the recurrence and survival rates when treating MCC with MMS and different clinical excision margins. MATERIALS AND METHODS: The MEDLINE, EMBASE, and CENTRAL databases were searched. Two independent reviewers selected studies that defined clear excision margins and either recurrence or survival. When possible, individual cases were extracted from case series and included in the analyses. Other studies were reviewed narratively. RESULTS: Overall, 1108 studies were identified; of which, 19 case series (168 cases) and 12 cohort studies were eligible. None of the cohort studies showed significant differences in recurrence or survival for either excision margins or MMS. Equally, logistic and Cox regression analyses of the case series revealed no significant differences in recurrence or survival between different excision margins and MMS. CONCLUSION: Synthesis of the available data does not indicate differences in recurrence and/or survival rates for MCC between different clinical excision margins and MMS