Quality control guidelines for amphotericin B, Itraconazole, posaconazole, and voriconazole disk diffusion susceptibility tests with nonsupplemented Mueller-Hinton Agar (CLSI M51-A document) for nondermatophyte Filamentous Fungi.

Although Clinical and Laboratory Standards Institute (CLSI) disk diffusion assay standard conditions are available for susceptibility testing of filamentous fungi (molds) to antifungal agents, quality control (QC) disk diffusion zone diameter ranges have not been established. This multicenter study documented the reproducibility of tests for one isolate each of five molds (Paecilomyces variotii ATCC MYA-3630, Aspergillus fumigatus ATCC MYA-3626, A. flavus ATCC MYA-3631, A. terreus ATCC MYA-3633, and Fusarium verticillioides [moniliforme] ATCC MYA-3629) and Candida krusei ATCC 6258 by the CLSI disk diffusion method (M51-A document). The zone diameter ranges for selected QC isolates were as follows: P. variotii ATCC MYA-3630, amphotericin B (15 to 24 mm), itraconazole (20 to 31 mm), and posaconazole (33 to 43 mm); A. fumigatus ATCC MYA-3626, amphotericin B (18 to 25 mm), itraconazole (11 to 21 mm), posaconazole (28 to 35 mm), and voriconazole (25 to 33 mm); and C. krusei, amphotericin B (18 to 27 mm), itraconazole (18 to 26 mm), posaconazole (28 to 38 mm), and voriconazole (29 to 39 mm). Due to low testing reproducibility, zone diameter ranges were not proposed for the other three molds.

Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida Species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion.

Fluconazole in vitro susceptibility test results for 256,882 isolates of Candida spp. were collected from 142 sites in 41 countries from June 1997 to December 2007. Data were collected for 197,619 isolates tested with voriconazole from 2001 to 2007. A total of 31 different species of Candida were isolated. Increased rates of isolation of the common non-albicans species C. glabrata (10.2% to 11.7%), C. tropicalis (5.4% to 8.0%), and C. parapsilosis (4.8% to 5.6%) were noted when the time periods 1997 to 2000 and 2005 to 2007 were compared. Investigators tested clinical isolates of Candida spp. by the CLSI M44-A disk diffusion method. Overall, 90.2% of Candida isolates tested were susceptible (S) to fluconazole; however, 13 of 31 species identified exhibited decreased susceptibility (<75% S), similar to that seen with the resistant (R) species C. glabrata and C. krusei. Among 197,619 isolates of Candida spp. tested against voriconazole, 95.0% were S and 3% were R. About 30% of fluconazole-R isolates of C. albicans, C. glabrata, C. tropicalis, C. rugosa, C. lipolytica, C. pelliculosa, C. apicola, C. haemulonii, C. humicola, C. lambica, and C. ciferrii remained S to voriconazole. An increase in fluconazole resistance over time was seen with C. parapsilosis, C. guilliermondii, C. lusitaniae, C. sake, and C. pelliculosa. Among the emerging fluconazole-R species were C. guilliermondii (11.4% R), C. inconspicua (53.2% R), C. rugosa (41.8% R), and C. norvegensis (40.7% R). The rates of isolation of C. rugosa, C. inconspicua, and C. norvegensis increased by 5- to 10-fold over the 10.5-year study period. C. guilliermondii and C. rugosa were most prominent in Latin America, whereas C. inconspicua and C. norvegensis were most common in Eastern European countries. This survey identifies several less-common species of Candida with decreased susceptibility to azoles. These organisms may pose a future threat to optimal antifungal therapy and underscore the importance of prompt and accurate species identification and antifungal susceptibility testing.

Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing.

Fluconazole in vitro susceptibility test results determined by the CLSI M44-A disk diffusion method for 11,240 isolates of noncandidal yeasts were collected from 134 study sites in 40 countries from June 1997 through December 2007. Data were collected for 8,717 yeast isolates tested with voriconazole from 2001 through 2007. A total of 22 different species/organism groups were isolated, of which Cryptococcus neoformans was the most common (31.2% of all isolates). Overall, Cryptococcus (32.9%), Saccharomyces (11.7%), Trichosporon (10.6%), and Rhodotorula (4.1%) were the most commonly identified genera. The overall percentages of isolates in each category (susceptible, susceptible dose dependent, and resistant) were 78.0%, 9.5%, and 12.5% and 92.7%, 2.3%, and 5.0% for fluconazole and voriconazole, respectively. Less than 30% of fluconazole-resistant isolates of Cryptococcus spp., Cryptococcus albidus, Cryptococcus laurentii, Trichosporon beigelii/Trichosporon cutaneum, Rhodotorula spp., Rhodotorula rubra/Rhodotorula mucilaginosa, and Rhodotorula glutinis remained susceptible to voriconazole. Emerging resistance to fluconazole was documented among isolates of C. neoformans from the Asia-Pacific, Africa/Middle East, and Latin American regions but not among isolates from Europe or North America. This survey documents the continuing broad spectrum of activity of voriconazole against opportunistic yeast pathogens but identifies several of the less common species with decreased azole susceptibility. These organisms may pose a future threat to optimal antifungal therapy and emphasize the importance of prompt and accurate species identification.

Geographic and temporal trends in isolation and antifungal susceptibility of Candida parapsilosis: a global assessment from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005.

We examined data from the ARTEMIS DISK Antifungal Surveillance Program to describe geographic and temporal trends in the isolation of Candida parapsilosis from clinical specimens and the in vitro susceptibilities of 9,371 isolates to fluconazole and voriconazole. We also report the in vitro susceptibility of bloodstream infection (BSI) isolates of C. parapsilosis to the echinocandins, anidulafungin, caspofungin, and micafungin. C. parapsilosis represented 6.6% of the 141,383 isolates of Candida collected from 2001 to 2005 and was most common among isolates from North America (14.3%) and Latin America (9.9%). High levels of susceptibility to both fluconazole (90.8 to 95.8%) and voriconazole (95.3 to 98.1%) were observed in all geographic regions with the exception of the Africa and Middle East region (79.3 and 85.8% susceptible to fluconazole and voriconazole, respectively). C. parapsilosis was most often isolated from blood and skin and/or soft tissue specimens and from patients hospitalized in the medical, surgical, intensive care unit (ICU) and dermatology services. Notably, isolates from the surgical ICU were the least susceptible to fluconazole (86.3%). There was no evidence of increasing azole resistance over time among C. parapsilosis isolates tested from 2001 to 2005. Of BSI isolates tested against the three echinocandins, 92, 99, and 100% were inhibited by concentrations of < or = 2 microg/ml of anidulafungin (621 isolates tested), caspofungin (1,447 isolates tested), and micafungin (539 isolates tested), respectively. C. parapsilosis is a ubiquitous pathogen that remains susceptible to the azoles and echinocandins; however, both the frequency of isolation and the resistance of C. parapsilosis to fluconazole and voriconazole may vary by geographic region and clinical service.

Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005.

Candida krusei is well known as a fungal pathogen for patients with hematologic malignancies and for transplant recipients. Using the ARTEMIS Antifungal Surveillance Program database, we describe geographic and temporal trends in the isolation of C. krusei from clinical specimens and the in vitro susceptibilities of 3,448 isolates to voriconazole as determined by CLSI (formerly NCCLS) disk diffusion testing. In addition, we report the in vitro susceptibilities of bloodstream infection isolates of C. krusei to amphotericin B (304 isolates), flucytosine (254 isolates), anidulafungin (121 isolates), caspofungin (300 isolates), and micafungin (102 isolates) as determined by CLSI broth microdilution methods. Geographic differences in isolation were apparent; the highest frequency of isolation was seen for the Czech Republic (7.6%) and the lowest for Indonesia, South Korea, and Thailand (0 to 0.3%). Overall, 83% of isolates were susceptible to voriconazole, ranging from 74.8% in Latin America to 92.3% in North America. C. krusei was most commonly isolated from hematology-oncology services, where only 76.7% of isolates were susceptible to voriconazole. There was no evidence of increasing resistance of C. krusei to voriconazole from 2001 to 2005. Decreased susceptibilities to amphotericin B (MIC at which 90% of isolates were inhibited [MIC(90)], 4 microg/ml) and flucytosine (MIC(90), 16 microg/ml) were noted, whereas 100% of isolates were inhibited by < or =2 microg/ml of anidulafungin (MIC(90), 0.06 microg/ml), micafungin (MIC(90), 0.12 microg/ml) or caspofungin (MIC(90), 0.25 microg/ml). C. krusei is an uncommon but multidrug-resistant fungal pathogen. Among the systemically active antifungal agents, the echinocandins appear to be the most active against this important pathogen.

Multicenter evaluation of a new disk agar diffusion method for susceptibility testing of filamentous fungi with voriconazole, posaconazole, itraconazole, amphotericin B, and caspofungin.

The purpose of this study was to correlate inhibition zone diameters, in millimeters (agar diffusion disk method), with the broth dilution MICs or minimum effective concentrations (MECs) (CLSI M38-A method) of five antifungal agents to identify optimal testing guidelines for disk mold testing. The following disk diffusion testing parameters were evaluated for 555 isolates of the molds Absidia corymbifera, Aspergillus sp. (five species), Alternaria sp., Bipolaris spicifera, Fusarium sp. (three species), Mucor sp. (two species), Paecilomyces lilacinus, Rhizopus sp. (two species), and Scedosporium sp. (two species): (i) two media (supplemented Mueller-Hinton agar [2% dextrose and 0.5 microg/ml methylene blue] and plain Mueller-Hinton [MH] agar), (ii) three incubation times (16 to 24, 48, and 72 h), and (iii) seven disks (amphotericin B and itraconazole 10-microg disks, voriconazole 1- and 10-microg disks, two sources of caspofungin 5-microg disks [BBL and Oxoid], and posaconazole 5-microg disks). MH agar supported better growth of all of the species tested (24 to 48 h). The reproducibility of zone diameters and their correlation with either MICs or MECs (caspofungin) were superior on MH agar (91 to 100% versus 82 to 100%; R, 0.71 to 0.93 versus 0.53 to 0.96 for four of the five agents). Based on these results, the optimal testing conditions for mold disk diffusion testing were (i) plain MH agar; (ii) incubation times of 16 to 24 h (zygomycetes), 24 h (Aspergillus fumigatus, A. flavus, and A. niger), and 48 h (other species); and (iii) the posaconazole 5-microg disk, voriconazole 1-microg disk, itraconazole 10-microg disk (for all except zygomycetes), BBL caspofungin 5-microg disk, and amphotericin B 10-microg (zygomycetes only).

Results from the ARTEMIS DISK Global Antifungal Surveillance study, 1997 to 2005: an 8.5-year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing.

Fluconazole in vitro susceptibility test results for 205,329 yeasts were collected from 134 study sites in 40 countries from June 1997 through December 2005. Data were collected for 147,776 yeast isolates tested with voriconazole from 2001 through 2005. All investigators tested clinical yeast isolates by the CLSI M44-A disk diffusion method. Test plates were automatically read and results recorded with a BIOMIC image analysis system. Species, drug, zone diameter, susceptibility category, and quality control results were collected quarterly. Duplicate (same patient, same species, and same susceptible-resistant biotype profile during any 7-day period) and uncontrolled test results were not analyzed. Overall, 90.1% of all Candida isolates tested were susceptible (S) to fluconazole; however, 10 of the 22 species identified exhibited decreased susceptibility (<75% S) on the order of that seen with the resistant (R) species C. glabrata and C. krusei. Among 137,487 isolates of Candida spp. tested against voriconazole, 94.8% were S and 3.1% were R. Less than 30% of fluconazole-resistant isolates of C. albicans, C. glabrata, C. tropicalis, and C. rugosa remained S to voriconazole. The non-Candida yeasts (8,821 isolates) were generally less susceptible to fluconazole than Candida spp. but, aside from Rhodotorula spp., remained susceptible to voriconazole. This survey demonstrates the broad spectrum of these azoles against the most common opportunistic yeast pathogens but identifies several less common yeast species with decreased susceptibility to antifungal agents. These organisms may pose a future threat to optimal antifungal therapy and emphasize the importance of prompt and accurate species identification.

Candida guilliermondii, an opportunistic fungal pathogen with decreased susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program.

Although a rare cause of invasive candidiasis, Candida guilliermondii has been reported to exhibit decreased susceptibility to antifungal agents. Aside from case reports and small surveys, there is little information regarding the epidemiology and antifungal susceptibility profile of C. guilliermondii. We report geographic and temporal trends in the isolation and antifungal susceptibilities of 1,029 C. guilliermondii clinical isolates collected from 127 medical centers as part of the ARTEMIS DISK Antifungal Surveillance Program. In addition, we report the in vitro susceptibility of 132 bloodstream isolates of C. guilliermondii to caspofungin. C. guilliermondii represented 1.4% of the 75,761 isolates collected from 2001 to 2003 and was most common among isolates from Latin America (3.7% versus 0.6 to 1.1%). Decreased susceptibility to fluconazole was noted (75% susceptible; range, 68 to 77% across regions), and voriconazole was more active in vitro against C. guilliermondii than fluconazole (91% susceptible; range, 88 to 93% across regions). Fluconazole was least active against isolates from dermatology (58%) and surgical (69%) services and against isolates associated with skin and soft tissue infection (68%, compared to 85% susceptible for bloodstream isolates). There was no evidence of increasing azole resistance over time among C. guilliermondii isolates tested from 2001 to 2003. Of 132 bloodstream isolates of C. guilliermondii tested against caspofungin, most were inhibited by < or =2 microg/ml (96%; MIC50/MIC90, 0.5/1.0 microg/ml). C. guilliermondii, a species that exhibits reduced susceptibility to fluconazole, is the sixth most frequently isolated Candida species from this large survey and may be an emerging pathogen in Latin America.

Candida rugosa, an emerging fungal pathogen with resistance to azoles: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program.

Candida rugosa is a fungus that appears to be emerging as a cause of infection in some geographic regions. We utilized the extensive database of the ARTEMIS DISK Antifungal Surveillance Program to describe the geographic and temporal trends in the isolation of C. rugosa from clinical specimens and the in vitro susceptibilities of 452 isolates to fluconazole and voriconazole. C. rugosa accounted for 0.4% of 134,715 isolates of Candida, and the frequency of isolation increased from 0.03% to 0.4% over the 6.5-year study period (1997 to 2003). C. rugosa was most common in the Latin American region (2.7% versus 0.1 to 0.4%). Decreased susceptibility to fluconazole (40.5% susceptible) was observed in all geographic regions; however, isolates from Europe and North America were much more susceptible (97 to 100%) to voriconazole than those from other geographic regions (55.8 to 58.8%). C. rugosa was most often isolated from blood and urine in patients hospitalized at the Medical and Surgical inpatient services. Notably, bloodstream isolates were the least susceptible to both fluconazole and voriconazole. C. rugosa should be considered, along with the established pathogens Candida krusei and Candida glabrata, as a species of Candida with reduced susceptibility to the azole antifungal agents.

Results from the ARTEMIS DISK Global Antifungal Surveillance Study: a 6.5-year analysis of susceptibilities of Candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing.

Fluconazole in vitro susceptibility test results for 140,767 yeasts were collected from 127 participating investigators in 39 countries from June 1997 through December 2003. Data were collected on 79,343 yeast isolates tested with voriconazole from 2001 through 2003. All investigators tested clinical yeast isolates by the CLSI (formerly NCCLS) M44-A disk diffusion method. Test plates were automatically read and results were recorded with the BIOMIC Vision Image Analysis System. Species, drug, zone diameter, susceptibility category, and quality control results were collected quarterly via e-mail for analysis. Duplicate (the same patient, same species, and same susceptible-resistant biotype profile during any 7-day period) and uncontrolled test results were not analyzed. The 10 most common species of yeasts all showed less resistance to voriconazole than to fluconazole. Candida krusei showed the largest difference, with over 70% resistance to fluconazole and less than 8% to voriconazole. All species of yeasts tested were more susceptible to voriconazole than to fluconazole, assuming proposed interpretive breakpoints of > or =17 mm (susceptible) and < or =13 mm (resistant) for voriconazole. MICs reported in this study were determined from the zone diameter in millimeters from the continuous agar gradient around each disk, which was calibrated with MICs determined from the standard CLSI M27-A2 broth dilution method by balanced-weight regression analysis. The results from this investigation demonstrate the broad spectrum of the azoles for most of the opportunistic yeast pathogens but also highlight several areas where resistance may be progressing and/or where previously rare species may be "emerging."

Correlation between radiographic transition zone and level of aganglionosis in Hirschsprung's disease: Implications for surgical approach.

BACKGROUND/PURPOSE: The anticipated level of aganglionosis can influence the surgical approach to Hirschsprung's disease. The aim of this study was to determine the accuracy of the contrast enema in predicting this level. METHODS: Over a 6-year period (1995 through 2000), 88 patients with Hirschsprung's disease underwent surgical correction. Preoperative contrast enema findings were available for 75 of these patients and were compared with operative and pathology reports. Data were analyzed by chi(2). RESULTS: The contrast enema showed a transition zone suggestive of Hirschsprung's disease in 67 of 75 patients (89%). In 59 of 67 (88%), the pathologic and radiographic transition zones were concordant. Seven of the 8 patients with discordant studies had total colonic (n = 5) or long-segment (n = 2) disease. Contrast enema correctly predicted the level of aganglionosis in 55 of 62 (89%) patients with rectosigmoid disease but only 4 of 13 (31%) of those with long-segment or total colonic disease (P <.01). Of the patients with a radiographic transition zone in the rectosigmoid, 54 of 60 (90%) had a matching level of aganglionosis. CONCLUSIONS: In rectosigmoid Hirschsprung's disease, the location of the radiographic transition zone correlates accurately with the level of aganglionosis in 90% of cases. However, the small incidence of discordance between anticipated level of aganglionosis and operative findings should be recognized, particularly when planning a one-stage transanal pull-through.

Uroepithelium in a colonic diverticulum.

Giant colonic diverticula are rare entities and often present in adulthood as acute diverticulitis. The authors present a case of giant colonic pseudodiverticulum lined with uroepithelium causing bowel obstruction in a neonate. The presence of uroepithelium in a colonic pseudodiverticuium remains unexplained and to the authors' knowledge unreported. This heterotopic tissue may be a result of an embryonic rest or could be urachal in origin adhering initially to the colon and eventually detaching from the umbilicus. These lesions should be resected because of the risk of infection, perforation, or obstruction.

The nonoperative management of fistula-in-ano.

BACKGROUND/PURPOSE: Fistulotomy is the accepted treatment for infants with perianal fistula. Although recurrence rates range from 0% to 68%. Based on the experience of a senior colleague who noted that babies suffering from perianal fistula follow a self-limited course the authors decided to determine if this observation was accurate. METHODS: A conservative approach to perianal abscess and fistula was used prospectively in 18 male infants. Abscesses were to be drained only if the baby was very uncomfortable or febrile. Once a fistula developed the authors continued observation until the fistula healed. Data are expressed as mean +/- SD. Mean follow-up period was 37 months. RESULTS: Mean age at onset of symptoms was 4 +/- 3 months. Fistulas developed in 14 patients (77%). All fistulas healed without operation. Four patients had abscesses drained for discomfort (n = 3) or fever (n = 1). No patient required antibiotics. Mean duration of symptoms was 6 +/- 4 months. Four patients in whom fistulas did not form healed after incision (n = 3) or spontaneous drainage (n = 1). All patients currently are asymptomatic. CONCLUSIONS: In healthy neonates, perianal abscess and fistula are self-limited conditions rarely requiring surgical drainage and not requiring antibiotics. The conservative management of perianal abscess and fistula in healthy infants appears to be safe and effective.

A double-blind comparison of fluconazole and nystatin in the prevention of candidiasis in patients with leukaemia. Antifungal Prophylaxis Study Group.

In this multicentre, randomised, double-blind study, the safety and efficacy of oral fluconazole (200 micrograms/day) and nystatin suspension (6,000,000 IU/day) for the prevention of fungal infections were compared in patients with leukaemia undergoing remission induction chemotherapy. Antifungal prophylaxis was initiated at the time chemotherapy was started and continued throughout the hospital stay or the period of neutropenia to a maximum of 42 days. Prophylaxis was successful (no evidence of fungal infection or fever of unknown origin unresponsive to antibiotics) in 38 of 56 (68%) fluconazole-treated and 25 of 53 (47%) nystatin-treated patients (P = 0.03). 2 patients (4%) in the fluconazole group and 6 (11%) patients in the nystatin group developed systemic fungal infections (P = 0.15). The overall frequency of adverse events was similar among fluconazole-treated (29%) and nystatin-treated (32%); most events in both treatment groups involved the gastrointestinal tract. These results indicated fluconazole was more effective than nystatin in preventing Candida infections in patients with leukaemia; fluconazole was well tolerated.

Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: a retrospective study of 60 patients and literature review.

Congenital diaphragmatic defects (CDDs) may occur in malformation syndromes of varied causes. Syndromic cases of CDDs due to chromosomal defects, autosomal recessive, autosomal dominant, or X-linked inheritance have been described. In order to determine the frequency and nature of syndromes, malformations, and chromosome abnormalities associated with CDDs, we reviewed the records of all patients with CDDs evaluated over a 4-year period. During the 4-year interval, a total of 60 patients was evaluated. Of these, 29 had a therapeutic or spontaneous abortion, and 31 received postnatal care. On prenatal ultrasonography, 20 of 60 (33%) of patients with CDDs had additional anomalies. Additional anomalies, besides CDDs, were present in 15 of 31 (48%) of liveborn patients on newborn evaluation. In total, 16 patients with multiple anomalies were evaluated. Of these, 12 of 16 (75%) had additional abnormalities detected by prenatal ultrasonography. The 4 of 16 (25%) without additional anomalies on prenatal sonography had multiple anomalies found neonatally, lethal multiple pterygium syndrome being diagnosed in one case. Prenatal chromosome analysis was performed in 7 of 16 patients, and all had postnatal karyotypes. All initial karyotypes were normal. Tetrasomy 12p was documented on postnatal fibroblast analysis in one case who had percutaneous umbilical blood sampling (PUBS). Syndromes diagnosed postnatally in 7 of 16 patients (44%) include: Fryns syndrome (2), Simpson-Golabi-Behmel syndrome (2), tetrasomy 12p (1), Brachmann-de Lange syndrome (1), and lethal multiple pterygium syndrome (1). We were unable to make a specific diagnosis in 9 of 16 patients (56%) with multiple malformations. In patients with CDDs, a normal prenatal karyotype, especially if obtained by PUBS, and absence of other detected abnormalities by fetal ultrasonography, do not exclude the presence of other major anomalies, including chromosome abnormalities and severe multiple malformation syndromes.

Neurodevelopmental outcome after open fetal surgery.

PURPOSE: This study examined the neurological and age-appropriate developmental outcomes of 11 children who underwent open fetal surgery. RESULTS: Nine children have normal neurological outcomes, and nine have normal development. CONCLUSION: Intensive postnatal care, intracranial hemorrhage, and requirement for prolonged respiratory support were associated with a worse neurological and developmental prognosis.

Chorioamniotic membrane separation: a potentially lethal finding.

Sonographic detection of chorioamniotic membrane separation (CMS) has been considered a benign incidental finding. We now report 6 cases of CMS identified by prenatal ultrasound; 1 in an otherwise normal pregnancy and 5 following fetal surgery. Following membrane separation, amniotic bands formed and compromised the umbilical cord in 4 cases leading to 2 fetal deaths. In the first case, CMS was detected by ultrasound at 22 weeks' gestation in an otherwise uncomplicated pregnancy. Because CMS was considered benign and umbilical cord blood flow was ample, the mother was followed by intermittent sonographic examinations. Fetal demise occurred 2 weeks later, clearly due to umbilical cord strangulation by an amniotic band. Surprised by this unexpected outcome, we reviewed our experience with CMS after hysterotomy for fetal surgery. Out of more than 40 fetal surgical cases, we have 5 cases in which CMS was recognized after hysterotomy. Three of these fetuses had umbilical cord compromise by a band of amniotic membrane leading to 1 fetal death. This experience demonstrates that membrane separation may be associated with amniotic band formation which can lead to cord strangulation and fetal compromise. Following fetal surgery, serial ultrasound evaluation and close fetal monitoring are indicated. In otherwise unremarkable pregnancies, clinician awareness of the possibility of amniotic band formation following CMS should be heightened. In either situation, knowledge of this potential life-threatening complication may identify cases in which cord compromise requires emergent delivery or fetoscopic release of the strangulating amniotic band.

Fetal hydrops after in utero tracheal occlusion.

In utero tracheal occlusion accelerates fetal lung growth in experimental animals. Following tracheal occlusion, animals with an intact diaphragm can develop hydrops; presumably the enlarged lungs increase intrathoracic pressure, compress the fetal heart, and occlude venous return. In contrast, in animals with a diaphragmatic hernia, even excessive lung expansion has not led to hydrops because the lung can expand through the diaphragmatic defect into the abdomen. The authors had assumed that the diaphragmatic defect in human fetuses with congenital diaphragmatic hernia would provide a similar "release valve" if excessive lung growth occurred. A recent case proved this assumption wrong. At 26 weeks' gestation, an in utero fetal tracheal occlusion was performed on a human fetus with a diaphragmatic hernia. Over the next 9 days there was rapid lung expansion and overdistention, compression of the fetal heart, and hydrops. These findings mimic those seen in fetuses with congenital high airway obstruction syndrome and has implications for in utero treatment of congenital diaphragmatic hernia.

Familial diaphragmatic agenesis: an autosomal-recessive syndrome with a poor prognosis.

Diaphragmatic agenesis is a severe form of congenital diaphragmatic hernia for which an autosomal recessive form of inheritance has been proposed. The authors report six families with 13 pregnancies with diaphragmatic agenesis in which inheritance followed an autosomal recessive pattern, including the first reported case of bilateral diaphragmatic agenesis in twins. None of the thirteen affected fetuses survived. Familial diaphragmatic agenesis appears to be a distinct clinical entity with a worse prognosis than posterolateral diaphragmatic hernia.