Tuberous sclerosis complex: neonatal deaths in three of four children of consanguineous, non-expressing parents.

We describe here four sibs, born to consanguineous, healthy, asymptomatic parents. Three of these infants had a rapidly fatal course in the neonatal period; death was attributed to congestive heart failure with radiographic evidence of cardiomegaly in all of them. Necropsy was done in only one of them and showed the typical findings of tuberous sclerosis complex (TSC) in the central nervous system (CNS), kidneys, heart, and liver. The fourth sib, currently 2 years old, also has typical signs of TSC, namely hypomelanotic skin macules and calcified subependymal nodules. Both parents and a living maternal grandmother had appropriate examination, which included skin inspection under Wood's lamp, dental examination, fundoscopy, echocardiography, abdominal and renal ultrasound, and head CT and MRI scans, and no signs of TSC were found in either parent or in the only living grandmother. By history alone there is no other relative with signs or symptoms suggestive of TSC. Linkage analysis and loss of heterozygosity (LOH) investigations on a variety of lesions obtained from postmortem and tissue or blood specimens from all available family members studied failed to identify a microdeletion in the chromosomal regions where TSC genes are located. It is very unusual that in a single TSC family there were three consecutive neonatal deaths, and very likely that all had cardiac rhabdomyomas. Moreover, to the best of our knowledge, there are no previous reports of TSC families with more than one affected sib, unusually severe manifestations of the disease, and completely normal, consanguineous parents.     

Biochemical and genetic evidence for phospholipase C activity in Mycobacterium ulcerans

This study reports the existence of phospholipase C and D enzymatic activities in Mycobacterium ulcerans cultures as determined by use of thin-layer chromatography to detect diglycerides in hydrolysates of radiolabeled phosphatidylcholine. M. ulcerans DNA sequences homologous to the genes encoding phospholipase C in Mycobacterium tuberculosis and Pseudomonas aeruginosa were identified by sequence analysis and DNA-DNA hybridization. Whether or not the phospholipase C and D enzymes of M. ulcerans plays a role in the pathogenesis of the disease needs further investigation.     

Membranous laryngotracheobronchitis,a complication of measles

Membranous laryngotracheobronchitis is a very serious infection which affects the larynx, trachea and bronchi, requiring aggressive therapeutic measures. It has been recently rediscovered as a cause of disease in children. However, it is a very unusual complication of measles. Two infants with measles and membranous laryngotracheobronchitis are reported.     

Cyclophosphamide, vincristine, adriamycin, and prednisone (CHOP) with and without intermediate dose methotrexate for the treatment of non-Hodgkin's lymphomas of diffuse histology

Seventy three patients with disseminated diffuse non-Hodgkin's lymphomas were treated with combinations of cyclophosphamide, vincristine sulfate, prednisone, and doxorubicin with and without 2 weekly doses of oral methotrexate in "intermediate" doses, followed by calcium leucovorin rescue. The addition of methotrexate did not increase the complete remission rate, the remission duration, or the survival (P value = 1.0, 0.74, and 0.78, respectively) in patients who did not have previous chemotherapy treatment. In previously treated patients, the complete remission rate was somewhat higher and the remission duration and survival were longer among those patients treated with the methotrexate containing program; however these differences were not statistically significant (P values = 0.88, 0.81, and 0.46, respectively). There was substantial morbidity and mortality during treatment with both treatment arms, among patients aged more than 60 years.     

Effect of a rhodium complex on alterations of hepatic function in thioacetamide-induced hyperplastic noduligenesis in rats

An in vivo model of liver hyperplastic noduligenesis was inducedin rats by long-term administration of thioacetamide (TAM) (50mg/kg/day i.p.). Three doses of 50 mg/kg of an antitumoral Rh(III)complex were administered at 14, 9 and 5 days before the endof TAM treatment. Plasma and urine were obtained from eitherTAM or Rh(III) complex or TAM plus Rh(III) complex treated ratsto determine the interactions of both substances with the biochemicalparameters related to liver function. The rise in alkaline phosphatase(ALP), teucine aminopeptidase (LAP), -gtutamyl transferase (GGT)and the unchanged activities in the aspartate and alanine aminotransferases(AST, ALT) in plasma of TAM-treated rats indicated that thedisease induced by this substance can be considered as a chronicobstructive biliary disease with indices of cell proliferationand tumors. The increased concentration of bilirubin both inthe plasma and urine of TAM-treated rats suggested liver cholestasisand hepatobiliary obstruction. The very low values of creatinineclearance indicated that there was some degree of kidney failuredue to the effect of TAM. The increased concentration of ammoniaboth in plasma and urine were probably a consequence of thedecreased flux in the urea cycle in the liver. The Rh(III) complexalone did not produce significant changes in the plasma enzymeactivities. The only significant changes were found in the concentrationsof uric acid and ammonia in the urine. When the Rh(III) complexwas administered to TAM-treated rats, significant restorationof the following parameters were observed: plasma enzymaticactivities, blood bilirubin and ammonia, uric acid and creatininein the urine and the creatinine clearance. These results suggestthat the altered liver function induced by TAM can be restoredby Rh(III) complex. The mechanisms by which this complex actsto counteract the TAM-induced changes are not yet established.     

Novel 6-Month Treatment for Drug-Resistant Tuberculosis,United States

The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose.     

Management of cervicofacial lymphatic malformations requires a multidisciplinary approach

Background/PurposeCervicofacial lymphatic malformations (CFLM) are rare, potentially life-threatening vascular anomalies, yet reports on multidisciplinary treatment strategies are lacking. We evaluated outcomes for CFLMs following sclerotherapy, surgical resection, and/or medical management.MethodsWe identified children with a CFLM at a vascular anomalies center from 2004 to 2019. Exclusion criteria: retro-orbital malformations, untreated malformations, patients without follow-up. Primary clinical outcome was contour improvement, with significance defined as LM volume reduction of > 50% by cross-sectional imaging.ResultsSixty-three children met inclusion criteria: 35 with macrocystic CFLMs, six with microcystic CFLMs, and 22 with mixed-type malformations. Mean post-intervention follow-up was 27.5 months. Fifty-eight patients underwent sclerotherapy (median: two treatments). Doxycycline and/or bleomycin were used in 95% of patients. After sclerotherapy, 97% of macrocystic CFLMs improved significantly compared to 82% of mixed and 67% of microcystic lesions. Sixteen children underwent surgical resection with 75% significantly improving; two additional patients were successfully treated with sclerotherapy after debulking surgery. Six children received sirolimus for microcystic disease, of which 33% significantly improved.ConclusionSclerotherapy is very effective for macrocystic components of CFLMs, albeit less so for microcystic disease. Microcystic CFLMs frequently require surgical resection. Sirolimus is a helpful therapeutic adjunct, particularly for microcystic lesions, but more study is needed.Level of EvidenceLevel II, prognosis study     

Short-term multiorgan metabolic benefits of rapid weight loss after sleeve gastrectomy in severely obese patients

BackgroundSleeve gastrectomy (SG) has become the most prevalent bariatric-metabolic surgical approach in the United States. Its popularity among surgeons and patients is mainly due to a better safety profile and less overall morbidity, with broad benefits from a systemic and metabolic perspective.ObjectiveComprehensively describe the short-term multiorgan metabolic effects of rapid weight loss after SG.SettingAcademic hospital, United States.MethodsWe retrospectively reviewed the charts of patients that underwent SG at our institution between 2012 and 2016. We analyzed the required variables to calculate multiple risk scores, such as cardiovascular, hypertension, and diabetes risk scores. Furthermore, the renal and hepatic functions and the metabolic and hematologic profiles were assessed at 12 months of follow-up.ResultsA total of 1002 patients were included in the analysis. The percentage of excess body mass index loss was, on average, 65% at 12 months of follow-up. We observed a positive cardio-renal-hepatic improvement, demonstrated by a substantial reduction of the 10-year cardiovascular risk. We noticed an improvement of renal function, which was more significant in chronic kidney disease (stage ≥2), and a significant improvement on liver function tests (measured by decreased aspartate aminotransferase and alanine transaminase) at 12 months of follow-up. Our data also show a positive impact on decreasing the risk of developing hypertension and type 2 diabetes. There was a positive impact on the lipid profile, with the exception of low-density lipoprotein.ConclusionThere are significant short-term benefits on multiorgan metabolic parameters after rapid weight loss in severely obese patients undergoing sleeve gastrectomy.