Carbimazole embryopathy-bilateral choanal atresia and patent vitello-intestinal duct: a case report and review of literature

BACKGROUND: In utero exposure to carbimazole for maternal hyperthyroidism has been reported to cause choanal atresia. There are case reports of patent vitello‐intestinal duct and Meckel's diverticulum in similar association. CASE: We report another such instance of an infant who was exposed to carbimazole in utero, presenting with bilateral choanal atresia and patent vitello‐intestinal duct. CONCLUSIONS: As there seems to be no reports of a possible association between propylthiouracil and congenital malformations, it may be safer to use propylthiouracil instead of carbimazole. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Acitretin embryopathy: a case report

BACKGROUND: Acitretin is an aromatic retinoid analog of vitamin A. Drugs of this group are well-known teratogenic agents. Nevertheless, acitretin embryopathy has been described only in fetuses. CASE: An infant was exposed to 10 mg/day of acitretin from the beginning of pregnancy until the 10th gestational week. At term, the newborn showed the following abnormalities: microcephaly, epicanthal folds, low nasal bridge, high palate, cup-shaped ears, anteverted nostrils, atrial septal defect, and bilateral sensorineural deafness. At 18 months of age, the patient showed microcephaly and neurodevelopmental delay. CONCLUSIONS: Our patient shows a pattern of anomalies resembling that observed in isotretinoin- and etretinate-exposed children. After ingestion, acitretin is partially converted into etretinate, and etretinate is partially metabolized into acitretin. A similar phenotype would therefore be expected after prenatal exposure to either drug. Moreover, in the present case, teratogenic effects were observed even though the dose was lower than in the previously reported acitretin embryopathy cases. Therefore, we propose that different retinoids, acitretin included, produce only one malformation pattern with variable phenotypic expression.     

Schistosomal appendicitis: Case series and systematic literature review

BackgroundGlobally, schistosomiasis affects at least 240 million people each year with a high proportion of cases in sub-Saharan Africa. The infection presents a wide range of symptoms mainly at the gastrointestinal and urogenital level. Cases of schistosomiasis-related appendicitis are seldom reported. The aim of the present study is to identify the prevalence of schistosomiasis-related appendicitis in Beira, Mozambique and compare to global prevalence.MethodsWe retrospectively reviewed all cases of appendicitis recorded from January 2017 to March 2020 at a single pathology department located in Beira in order to assess the prevalence of schistosomiasis. Moreover, we performed a systematic review on the prevalence of schistosomiasis-related appendicitis in all countries.FindingsA total of 145 appendicitis cases in Beira showed a 13.1% prevalence of schistosomal-related appendicitis. The mean age of patients was 29.1 years, and 14 (73.7%) were male. The systematic review identified 20 studies with 34,790 inpatients with schistosomiasis-related appendicitis with a global prevalence of 1.31% (95% confidence interval (CI): 0.72 to 2.06); a high heterogeneity (I² = 96.0%) was observed. Studies carried out in Africa reported a significantly higher prevalence of schistosomiasis-related appendicitis (2.75%; 95% CI: 1.28 to 4.68) than those in Middle East (0.49%; 95% CI: 0.18 to 0.95) (p for interaction < 0.0001).ConclusionsSchistosomiasis infection should be considered as possible cause of appendicitis not only in endemic areas but also in developed countries. Considering that prevention is the best way to control the infection, more efforts should be put in place in order to increase the prevention coverage and avoid the cascading implications for health. This is even more so important in this Coronavirus Disease 2019 (COVID-19) era where the majority of attention and funds are used to fight the pandemic.     

Caspase‐8: a key role in the pathogenesis of diabetic embryopathy

Maternal diabetes causes neural tube defects in embryos, which are associated with increased apoptosis in the neuroepithelium. Many factors, including effector caspases, have been shown to be involved in the events. However, the key regulators have not been identified and the underlying mechanisms remain to be addressed. Caspase‐8, an initiator caspase, has been shown to be altered in diabetic embryopathy, suggesting a role as an upstream apoptotic regulator. Using mouse embryos as a model system, this study demonstrates that caspase‐8 is required for the production of hyperglycemia‐associated embryonic malformations. Caspase‐8 was shown to be expressed in the developing neural tube. Its activity, as evidenced by enhanced cleavage, was increased by hyperglycemia. These changes were associated with increased formation of the active cleavage of Bid. Inhibition of caspase‐8 activity in high glucose–challenged embryos reduced the rate of embryonic malformation and this was associated with decreased apoptosis in the neuroepithelium of the neural tube. Inhibition of caspase‐8 activity also reduced hyperglycemia‐induced Bid activation and caspase‐9 cleavage. These data suggest that caspase‐8 may control diabetic embryopathy‐associated apoptosis via regulation of the Bid‐stimulated mitochondrion/caspase‐9 pathway. Birth Defects Res (Part B)86:72‐77, 2009. ©2009 Wiley‐Liss, Inc.     

Cardiac malformations and alteration of TGFβ signaling system in diabetic embryopathy

BACKGROUND : Cardiovascular defects are the most common anomalies in diabetic embryopathy. The mechanisms underlying the manifestation of the defects remain to be addressed. METHODS : Female mice were administered streptozotocin to induce diabetes. Embryos from euglycemic (control) and hyperglycemic groups were examined for morphological and histological evaluation of malformations. Cell proliferation and programmed cell death (apoptosis) were assessed using mitotic markers (BrdU and Ki67) and TUNEL assay, respectively. Expression of eight four genes in the TGFβ signaling system was analyzed using real‐time RT‐PCR. RESULTS : Structural abnormalities were observed in the heart and neural tube in diabetic groups, with significantly higher malformation rates than in control groups. Moreover, malformation rates in the heart were higher than those in the neural tube. Cardiac abnormalities including dilated heart tube, smaller ventricles, conotruncal stenosis, and abnormal heart looping were seen during early morphogenesis prior to cardiac septation [embryonic day (E) 9.5–11.5]. Histological examinations showed hypoplastic myocardium and endocardial cushions. After cardiac septation (E15.5), ventricular septal defects were observed, which were manifested in the non‐muscular portion of the septum. Significant decreases in cell proliferation with no differences in apoptosis were observed in the myocardium and endocardial cushions in diabetic compared to control groups. Factors in the TGFβ signaling that regulate heart development were downregulated by maternal diabetes. CONCLUSIONS : Maternal diabetes causes malformations in the heart of the embryo. The heart is more susceptible to maternal diabetic insults than the neural tube. Malformations in the heart prior to septation are associated with decreased cell proliferation, but not increased apoptosis. The TGFβ signaling is involved in cardiac malformations in diabetic embryopathy. Birth Defects Res (Part B) 89:97–105, 2010. © 2010 Wiley‐Liss, Inc.     

Cold urticaria: case series and literature review

Cold urticaria is one of the five most common causes of chronic urticaria and is grouped as a physical urticaria. It can occur after exposure to cold, either through solid objects, air or liquids. Patients may have symptoms of urticaria, angioedema, respiratory distress and even anaphylaxis when the skin is exposed to a cold environment, such as handling refrigerated objects, swimming in cold water or entering an air-conditioned room. Five cases of cold urticaria are presented, followed by a brief literature review.     

Evaluation of olfactory and auditory system effects of the antihyperthyroid drug carbimazole in the Long-Evans rat

Carbimazole (2-carbethoxythio-1-methylimidazole) is a thiocarbamide drug used in the treatment of hyperthyroidism in humans. Side effects associated with carbimazole treatment are reported to include impaired taste, impaired olfaction, and hearing loss. The structurally similar antihyperthyroid drug methimazole (1-methyl-2-mercaptoimidazole), also reportedly associated with impaired taste and olfaction in humans, has recently been demonstrated by this laboratory to be an olfactory toxicant by both the oral and intraperitoneal routes of exposure in rodents. A systematic evaluation of sensory system effects of these compounds, either in rodents or humans, is not available in the literature. Male Long-Evans rats were used to evaluate the auditory and olfactory toxicity of carbimazole by two routes of exposure. Histopathological evaluation of nasal cavities from rats administered carbimazole via i.p. and oral routes revealed olfactory mucosal damage and early evidence of repair; a no-observed effect level (NOEL) of 100 mg/kg was observed for orally administered carbimazole. Further, these studies demonstrate evidence for the generation of the olfactory toxic metabolites of carbimazole by the olfactory mucosa itself, as incubation of carbimazole with an olfactory S9 preparation resulted in NADPH-dependent degradation of carbimazole. Evaluation of the auditory startle response in carbimazole-treated rats revealed no deficits, demonstrating that carbimazole does not cause a global loss of hearing in rats. © 1998 John Wiley & Sons, Inc. J Biochem Toxicol 12: 305–314, 1998     

Stewart-Treves syndrome: Case report and literature review

Lymphangiosarcoma, or Stewart-Treves Syndrome (STS), is a very rare skin angiosarcoma with poor prognosis, which usually affects the upper limbs of patients who underwent breast cancer surgery, including axillary dissection followed by radiotherapy (RT). Cutaneous lymphangiosarcomas, which account for approximately 5% of all angiosarcomas, usually originate in the limb with chronic lymphedema. Lymphatic blockade is involved in the onset of STS. RT contributes indirectly to an increased risk of developing STS by causing axillary-node sclerosis and resulting in a lymphatic blockade and lymphedema. Chronic lymphedema causes local immunodeficiency, which indirectly leads to oncogenesis. Currently, axillary nodes are no longer routinely irradiated after axillary dissection, which is associated with a reduction in the incidence of chronic lymphedema from 40% to 4%. The use of sentinel lymph node biopsy technique is also widespread and the associated risk of lymphedema is further reduced. Thus, the incidence of STS decreased significantly with improved surgical and radiation techniques. The overall prognosis of STS patients is very poor. Only early radical surgical removal, including amputation or disarticulation of the affected limb, or wide excision at an early stage offers the greatest chance of long-term survival. Only a few case reports and series with a small number of patients with lymphangiosarcoma can be found in the literature. We present a case report of the first diagnosed STS at our department in an effort to highlight the need of the consideration of developing lymphangiosarcoma in patients with chronic lymphedema.     

Fatigue sacral fractures: A case series and literature review

Objectives:Fatigue sacral fractures (FSFs) are rare and often misdiagnosed. This study presents a series of FSFs and a meticulous literature review.Methods:The present is an 11-year (2010-2021) retrospective observational study. The characteristics of all adult patients with FSF, including demographics, fracture type, treatment, history of fatigue fracture and imaging were evaluated.Results:Eight cases (6 females; 75%), suffering from 12 fractures (4 bilateral cases) with mean age=33.4 years were studied. Two patients (25%) had suffered another fatigue fracture in the past. Mean symptoms’ duration prior diagnosis was 8.5 weeks, while mean symptoms’ duration after diagnosis was 10.75. In most cases (7; 87.5%), MRI revealed the fracture. According to the Kaeding-Miller classification; five fractures (42%) were grade III, four (33%) IV and three (25%) II. All patients were treated conservatively, with rest and analgesics, while three received vitamin D and calcium. One patient, due to delayed union, was commenced on teriparatide.Conclusions:FSFs are often misdiagnosed; therefore, they should be included in the differential diagnosis for chronic low back-or-hip pain in athletes. History of other fatigue injuries seems to be a predisposing factor. It is of paramount importance to obtain advanced imaging for identifying a FSF.     

Podocyturia as an early diagnostic marker of preeclampsia: a literature review

Context: Preeclampsia (PE) is a pregnancy-related disease, and it is a leading cause of maternal and neonatal morbidity and mortality. It is characterized by the new onset of hypertension after 20?weeks of gestation together with signs of organ damage, most commonly the kidneys. The treatment of PE is symptomatic and final intervention requires delivery, regardless of the gestational age of the foetus. Furthermore, PE is a risk factor for developing cardiovascular disease and chronic kidney disease – even many years after the delivery.

Objective: Current research of PE has revealed that detection of podocytes in urine (podocyturia) could be a useful method for both confirmation of PE diagnosis and for the prediction of the severity of the disease.

Conclusion: The main aim of this review is to summarize the current state of available methods for podocyte detection and to discuss their relevance in clinical practice.     

Saksenaea vasiformis infections: Case report and literature review

Since the first human infection by Saksenaea vasiformis in 1976 another 26 cases have been reported. Here is a report of a new case which involved an Ecuadorian adolescent who suffered serious burns after a car accident. It developed as a localized cutaneous infection which was successfully treated with surgical debridement and amphotericin B. This is the second report of this infection from South America and the third involving a burn patient. The previously reported 27 cases are reviewed.     

Hyperinflammation after anti-SARS-CoV-2 mRNA/DNA vaccines successfully treated with anakinra: Case series and literature review

The current SARS-CoV-2 pandemic diffused worldwide has encouraged the rapid development of vaccines to counter the spread of the virus. At present in Italy, 75.01% of the population completed the vaccination course (AIFA.gov.it) and very few adverse events have been recorded by now. Side-effects related to a theoretical over-reaction of the immune system in response to vaccines administration have been described, and the possibility that an autoimmune or a hyperinflammatory condition may occur was recently observed. Herein, we report four cases of hyperinflammatory syndrome with features indicative of Adult-onset Still’s disease (AOSD) and macrophage activation syndrome (MAS), occurred after anti-SARS-CoV-2 vaccine injection and seen at our Unit between March and May 2021. Since interleukin (IL)-1 is one of the pivotal cytokines involved in AOSD pathogenesis, the inhibition of IL-1 is crucial in ameliorating the clinical symptoms of those patients. Moreover, it has been highlighted the central role of IL-1 as a hallmark of the hyperinflammatory status elicited by SARS-CoV-2 infection. In this case series, we successfully employed the IL-1 receptor antagonist anakinra to curb the cytokine release likely unleashed by the vaccine stimulation in potentially predisposed subjects. We also made a literature search to detect other patients with hyperinflammation temporally related to vaccines injection who benefited from IL-1 inhibition, while other AOSD/MAS-like described syndromes improved with other immunomodulatory strategies.     

Ring chromosome 6: Case report and review of literature

Summary A ring chromosome 6 has been identified by GTG-banding in a male with microcephaly, growth retardation, seizures, epicanthus, hypertelorism, micrognathia, and other congenital anomalies. Cytogenetic studies indicate the instability of the ring chromosome. The most common findings in subjects with ring 6 include: profound to moderate mental retardation, microcephaly, prenatal growth failure, retarded bone age, epicanthal folds, flat nasal bridge, short neck, ears low-set or malformed, microphthalmia, and micrognathia. Linkage studies, including HLA, are consistent with reported maps of chromosome 6.This study was supported in part by grant number 1-442 from the National Foundation — March of Dimes     

Prostate embryonal rhabdomyosarcoma in adults: Case report and review of literature

Introduction

Prostate embryonal rhabdomyosarcoma (ERMS) is a common tumour in infants and children, with a median occurrence age of 5 years, but it is rare in adults. It is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethral obstruction, and systemic spread, commonly to the lungs, liver and bone. Several therapeutic approaches have been employed in the effort to treat prostate ERMS, but all of them have failed to gain a significant survival benefit in adult patients.

Case report

We report on a case of a stage IV prostate ERMS, approached with combined-modality treatment, with the administration of 5 courses of doxorubicin, ifosfamide and 2-mercaptoethane sulfonate sodium (mesna), and, subsequent radiotherapy to the prostatic bed (60 Gy/30 fxs). The patient remained free of progression of disease for about 1 year to finally experience a systemic relapse with multiple lung metastases and pleural effusion. The patient died for metastatic disease 27 months following the initial diagnosis.

Conclusion

While it remains questionable which therapeutic approach for prostate ERMS in adults is the most appropriate, our report demonstrates that a chemo-radiation combined treatment can control the prostate disease, reducing the symptoms and improving the quality of life of these patients, for the most part destined to die for systemic progression of disease.