Indian child with novel variant in OFD1 gene

Orofaciodigital syndrome (OFD) can have variable phenotype and presents with oral anomalies, facial dysmorphism, and digital malformations like syndactyly, and polydactyly. Other presentations also include renal and cardiac defects, and central nervous system anomalies like hydrocephalus and cerebellar abnormalities. OFD1 is a X‐linked dominant form of the syndrome presenting in females with mutations in CXorf5 or OFD1 gene. We describe a young child with sparse hairs, milia over face and absence of corpus callosum. Next generation sequencing showed frameshift pathogenic variant in the exon 13 of the OFD1 gene, consistent with diagnosis of OFD1.     

Intracranial peripheral primitive neuroectodermal tumors of the cavernous sinus: a diagnostic peculiarity

Peripheral primitive neuroectodermal tumors (pPNETs) are aggressive, poorly differentiated neoplasms that occur in children and young adults. These tumors are associated with a peak incidence in the second decade and a slight male preponderance. Recently, Ewing sarcoma and pPNET tumors have been proven to carry identical translocations, the most common being t(11;22)(q24;q12). Intracranial Ewing sarcoma/pPNETs have rarely been described in the literature. We studied a case of intracranial pPNET arising in the right cavernous sinus of a 46-year-old man. On imaging, the tumor had both sellar and suprasellar components and was centered within the right parasellar region. Histologically, the tumor was composed of intermediate to large cells with round to oval hyperchromatic nuclei with distinct nucleoli. The cells contained a moderate amount of slightly basophilic cytoplasm. The tumor was markedly fibrotic and had collagen bands surrounding both individual and groups of cells. A large immunohistochemical panel was positive only for CD99 and vimentin. Fluorescence in situ hybridization did not show translocations associated with Ewing sarcoma/pPNET. However, a small percentage of these tumors can be negative for this translocation. In these cases, histology and immunohistochemical techniques in the absence of an alternative diagnosis are the only tools available to establish the diagnosis.     

Effectiveness and appropriateness of empiric metronidazole for Clostridium difficile-associated diarrhea

OBJECTIVE: Although Clostridium difficile is the most common infectious etiology of nosocomial diarrhea, noninfectious causes are far more common. Empiric initiation of therapy for all patients is of unknown value. The aim of this study was to determine benefits of empiric metronidazole for Clostridium difficile-associated diarrhea (CDAD). METHODS: We conducted a 4-month prospective surveillance of all patients in two community teaching hospitals receiving metronidazole for empiric treatment of presumptive CDAD. A database including antibiotic usage, fever, white blood cell count, feeding formula usage, comorbidity, and response to therapy was maintained. RESULTS: Seventy-one patients on the medical (50), surgical (18), obstetric (two), and trauma (one) service were identified. Sixty-two had nosocomial diarrhea; nine had diarrhea on admission. Seventy (97%) received antibiotics; one (3%) was on nelfinavir only. Eighteen (25%) were subsequently proven to have CDAD; two (3%) had laxative-induced diarrhea; two (3%) had diarrhea secondary to a medication (colchicine [one] and nelfinavir [one]); one (1%) had diarrhea caused by bowel preparation for colonoscopy. The remaining 49 (68%) did not have a clearly established diarrhea etiology. (Four did not undergo stool examination.) Statistical analysis (chi(2) test) demonstrated a significant decrease in symptoms for metronidazole-treated patients with CDAD versus those with a different diagnosis (p = 0.05). Not surprisingly, multivariate regression analysis identified a strong correlation of diagnosing CDAD with age >60 yr, antibiotics exposure, fever, elevated white blood cell count, and resolution of symptoms with specific metronidazole treatment. CDAD was definitively diagnosed in 25% of our hospitalized patients with diarrhea, consistent with published data. Although some cases might have been missed, most patients did not have CDAD and received no benefit (and were potentially harmed) by empiric metronidazole. There was no way a priori to distinguish CDAD from non-CDAD. CONCLUSIONS: In the absence of clear guidelines, empiric metronidazole should be reserved for strongly presumptive CDAD patients (older patients with comorbid conditions receiving broad-spectrum antibiotics associated with CDAD) who cannot hemodynamically or otherwise tolerate diarrhea. Used judiciously, empiric therapy may more rapidly resolve symptoms, and could conceivably prevent/abate severe complications and nosocomial spread.     

Transcatheter aortic valve replacement in patients with severe aortic stenosis and heart failure

Severe aortic stenosis (AS) and heart failure (HF) represent an important and high-risk group of patients who are often referred for transcatheter aortic valve replacement (TAVR) due to high risk for surgical intervention. Thus far, randomized controlled trials have shown comparable outcomes between TAVR and surgical aortic valve replacement in patients with severe AS and heart failure with reduced ejection fraction. In the current review, we will discuss (1) the pathophysiology of HF in patients with severe AS, (2) role of imaging modalities in management, (3) role of biomarkers of HF on prognosis, (4) impact of other valvular heart diseases, (5) evidence from the contemporary trials on the role of TAVR in patients with severe AS and HF, and (6) future directions and research.