The effect of Covid-19 mRNA vaccine on serum anti-Müllerian hormone levels.

STUDY QUESTION: Does the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have an association with ovarian reserve as expressed by circulating anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER: Ovarian reserve as assessed by serum AMH levels is not altered at 3 months following mRNA SARS-CoV-2 vaccination. WHAT IS KNOWN ALREADY: A possible impact of SARS-CoV-2 infection or vaccination through an interaction between the oocyte and the somatic cells could not be ruled out, however, data are limited. STUDY DESIGN, SIZE, DURATION: This is a prospective study conducted at a university affiliated tertiary medical center between February and March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study population included reproductive aged women (18-42 years) that were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart). Women with ovarian failure, under fertility treatments, during pregnancy, previous Covid-19 infection or vaccinated were excluded from the study. Blood samples were collected for AMH levels before the first mRNA vaccine administration. Additional blood samples after 3 months were collected for AMH and anti-Covid-19 antibody levels. Primary outcome was defined as the absolute and percentage change in AMH levels. MAIN RESULTS AND THE ROLE OF CHANCE: The study group consisted of 129 women who received two mRNA vaccinations. Mean AMH levels were 5.3 (±SD 4.29) µg/l and 5.3 (±SD 4.50) µg/l at baseline and after 3 months, respectively (P = 0.11). To account for possible age-specific changes of AMH, sub-analyses were performed for three age groups: <30, 30-35 and >35 years. AMH levels were significantly lower for women older than 35 years at all times (P = 0.001 for pre and post vaccination AMH levels versus younger women). However, no significant differences for the changes in AMH levels before and after vaccinations (Delta AMH) were observed for the three age groups (P = 0.46). Additionally, after controlling for age, no association was found between the degree of immunity response and AMH levels. LIMITATIONS, REASONS FOR CAUTION: Although it was prospectively designed, for ethical reasons we could not assign a priori a randomized unvaccinated control group. This study examined plasma AMH levels at 3 months after the first vaccination. It could be argued that possible deleterious ovarian and AMH changes caused by the SARS-CoV-2 mRNA vaccinations might take effect only at a later time. Only longer-term studies will be able to examine this issue. WIDER IMPLICATIONS OF THE FINDINGS: The results of the study provide reassurance for women hesitant to complete vaccination against Covid 19 due to concerns regarding its effect on future fertility. This information could be of significant value to physicians and patients alike. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by Sheba Medical Center institutional sources. All authors have nothing to disclose. TRIAL REGISTRATION NUMBER: The study protocol was approved by the 'Sheba Medical Center' Ethical Committee Review Board (ID 8121-21-SMC) on 8 February 2021 and was registered at the National Institutes of Health (NCT04748172).

Adnexal torsion recurrence-is the adnexal twist degree a risk factor? A retrospective cohort study.

OBJECTIVE: To evaluate whether the adnexal twist degree is related to torsion recurrence and whether there is a dose-dependent correlation. DESIGN: A retrospective cohort study. SETTING: Single tertiary medical centre. POPULATION: The study includes non-pregnant patients operated, for the first time, for adnexal torsion, between 2011 and 2018. METHODS: Information regarding the degree of adnexal twist was collected from surgical reports. Recurrence was identified using a computerised database and ascertained via telephone with a response rate of 87.2% (253/290). MAIN OUTCOME MEASURES: Adnexal torsion recurrence rate. RESULTS: A total of 182 women who had undergone laparoscopic detorsion met the inclusion criteria. Twenty-two had torsion recurrence (12.1%). Adnexal twist degree in the primary event was associated with a higher recurrence risk: 4.3% of women with twist degree ≤360 (n = 3/70), 14.5% of women with twist degree of 361-720 (n = 9/62) and 20% of women with twist degree >720 (n = 10/50) (P = 0.03). The median twist degree was 540 (interquartile range [IQR] 360-855) and 720 (IQR 675-1080) degrees in the control and study groups, respectively (P = 0.005). Additional possibly associated factors for recurrence were evaluated. Age emerged as a possible risk factor, with a median age of 19 years in the recurrence group (IQR 14-27 years) versus 28.5 (IQR 19-36 years) in the non-recurrence group (P < 0.01). Logistic regression analysis revealed that together with age, adnexal twist degree remained significantly associated with torsion recurrence (odds ratio [OR] 1.98, 95% CI 1.09-3.61; P = 0.02). CONCLUSION: Adnexal twist degree was found to be positively associated with the risk of torsion recurrence. TWEETABLE ABSTRACT: Adnexal twist degree was found to be positively associated with the risk of torsion recurrence.

Eustachian tube dysfunction leading to middle-ear pathology in patients on chronic mechanical ventilation.

OBJECTIVE: This study aimed to investigate the prevalence of and risk factors for Eustachian tube dysfunction leading to middle-ear pathology in patients on chronic mechanical ventilation via tracheostomy tube. METHODS: A total of 40 patients on chronic ventilation were included in a prospective cohort study. Middle-ear status was determined by tympanometry. Tympanograms were categorised as types A, B or C; types B and C were defined as middle-ear pathology. RESULTS: In all, 57 ears of 40 patients were examined. Disease was found in at least 1 ear in 26 out of 40 patients. Middle-ear pathology was found in 25 out of 34 patients who were tube fed (via nasogastric tube or percutaneous endoscopic gastrostomy) vs 1 patient out of the 6 fed orally (p = 0.014), and in 23 out of 31 with conscious or cognitive impairment vs 3 out of 9 cognitively intact patients (p = 0.044). CONCLUSION: Middle-ear pathology is common in patients on chronic mechanical ventilation via tracheostomy tube. The highest prevalence was in those with impaired consciousness or cognition, and oral feeding appeared protective.

16(th) IHIW : review of HLA typing by NGS.

Human leucocyte antigen (HLA) genes play an important role in the success of organ transplantation and are associated with autoimmune and infectious diseases. Current DNA-based genotyping methods, including Sanger sequence-based typing (SSBT), have identified a high degree of polymorphism. This level of polymorphism makes high-resolution HLA genotyping challenging, resulting in ambiguous typing results due to an inability to resolve phase and/or defining polymorphisms lying outside the region amplified. Next-generation sequencing (NGS) may resolve the issue through the combination of clonal amplification, which provides phase information, and the ability to sequence larger regions of genes, including introns, without the additional effort or cost associated with current methods. The NGS HLA sequencing project of the 16IHIW aimed to discuss the different approaches to (i) template preparation including short- and long-range PCR amplicons, exome capture and whole genome; (ii) sequencing platforms, including GS 454 FLX, Ion Torrent PGM, Illumina MiSeq/HiSeq and Pacific Biosciences SMRT; (iii) data analysis, specifically allele-calling software. The pilot studies presented at the workshop demonstrated that although individual sequencers have very different performance characteristics, all produced sequence data suitable for the resolution of HLA genotyping ambiguities. The developments presented at this workshop clearly highlight the potential benefits of NGS in the HLA laboratory.

Early sensory over-responsivity in toddlers with autism spectrum disorders as a predictor of family impairment and parenting stress.

BACKGROUND: Sensory over-responsivity (SOR) affects many individuals with autism spectrum disorders (ASD), often leading to stressful encounters during daily routines. METHODS: This study describes the associations between early SOR symptoms and the longitudinal course of restrictions in family life activities and parenting stress across three time-points in families raising a child with ASD (n = 174). Covariates were child diagnostic severity, emotional problems, and maternal affective symptoms. At time 1 mean chronological age was 28.5 months. Children were administered the Autism Diagnostic Observation Schedule (ADOS) and Mullen Scales of Early Learning (MSEL). Parents completed the Infant Toddler Sensory Profile (ITSP), Infant-Toddler Social Emotional Assessment (ITSEA), Beck Anxiety Index (BAI), and the Center for Epidemiologic Studies Depression Inventory (CES-D) at time 1; and the Parenting Stress Index (PSI) and Family Life Impairment Scale (FLIS) at the three annual time-points. RESULTS: Latent Growth Curve Models indicated that higher SOR scores on the ITSP at time 1 were associated with higher initial levels of family life impairment and parenting stress and with a smaller magnitude of change over time. These associations were independent of severity of ADOS social-communication symptoms, MSEL composite score, ITSEA externalizing and anxiety symptoms, and maternal affective symptoms as measured by the BAI and CES-D. On average FLIS and PSI did not change over time, however, there was significant individual variability. Concurrently, SOR at time 1 explained 39-45% of the variance in family stress and impairment variables. CONCLUSIONS: An evaluation of SOR should be integrated into the assessment of toddlers with ASD considering their role in family life impairment and stress.

Filling the gaps - the generation of full genomic sequences for 15 common and well-documented HLA class I alleles using next-generation sequencing technology.

Many common and well-documented (CWD) HLA alleles have only been partially characterized. The DNA sequence of these incomplete alleles, as published in the IMGT/HLA database, is most often limited to exons that code for the extracellular domains of the mature protein. Here we describe the application of next-generation sequencing technology to obtain full length genomic sequence from a single long-range PCR amplicon for 15 common and well-documented HLA Class I alleles. This technology is well suited to fill in the gaps of the current HLA allele sequence database which is largely incomplete. A more comprehensive catalog of HLA allele sequences would be beneficial in the evaluation of mismatches in transplantation, studies of population genetics, the evolution of HLAs, regulatory mechanisms and HLA expression, and issues related to the genomic organization of the MHC.

Sensory over-responsivity in elementary school: prevalence and social-emotional correlates.

Sensory over-responsivity (SOR) towards tactile and auditory input can impact children's participation in academic and social activities; however the prevalence of SOR behaviors and their relation to social-emotional problems and competence has not been rigorously studied. This study investigated SOR in a representative sample of elementary school-aged children (n = 925, 50% boys, ages 7-11 years) who were followed from infancy. Sixteen percent of parents reported that at least four tactile or auditory sensations bothered their children. Being bothered by certain sensations was common while others were relatively rare. Parents of children with versus without elevated SOR in school-age reported higher frequencies of early and co-occurring internalizing, externalizing, and dysregulation problems, and lower levels of concurrent adaptive social behaviors. Early identification of elevated SOR and assessment of concurrent social-emotional status are important to minimize their impact on social adaptive behaviors at school age.

Sensory clusters of toddlers with autism spectrum disorders: differences in affective symptoms.

BACKGROUND: Individuals with autism spectrum disorders (ASDs) show variability in their sensory behaviors. In this study we identified clusters of toddlers with ASDs who shared sensory profiles and examined differences in affective symptoms across these clusters. METHOD: Using cluster analysis 170 toddlers with ASDs were grouped based on parent rating of the Infant Toddler Sensory Profile (Dunn, 2002) under-responsivity, over-responsivity, and seeking scales. Affective symptoms were evaluated with the Infant Toddler Social Emotional Assessment (Carter & Briggs-Gowan, 2005). RESULTS: Three clusters were identified: (1) low frequency of sensory symptoms (n = 44); (2) high frequency of symptoms (n = 49); and (3) mixed (n = 77); high frequency of under-and over-responsivity and low frequency of seeking). Relative to the low frequency cluster, parents rated toddlers in the high frequency and mixed clusters (both characterized by high frequencies of sensory under- and over-responsivity) as higher on negative emotionality, depression, and anxiety symptoms. Sensory and affective differences among clusters remained after co-varying severity of ASD symptoms. CONCLUSIONS: Interdisciplinary assessments are recommended for toddlers with ASDs in order to identify the interplay of sensory and affective symptoms.

Intraoperative localization of thoracic spine level with preoperative percutaneous placement of intravertebral polymethylmethacrylate.

OBJECTIVE: To evaluate the safety and utility of preoperative vertebroplasty for intraoperative localization of thoracic spinal levels. SUMMARY OF BACKGROUND DATA: Intraoperative fluoroscopy or plain radiographs are traditionally used to localize thoracic spine levels during thoracic spine operations. Unfortunately, such localization can occasionally be difficult in the midthoracic levels due to lack of landmarks, scapular shadows, and the body habitus of the morbidly obese. There are multiple techniques described in the literature that allow for preoperative localization of thoracic spinal levels during approaches to the posterior thoracic spine. For efficient and accurate intraoperative localization of thoracic spinal levels during anterior thoracic spine procedures, we describe a method that uses preoperative percutaneous placement of polymethylmethacrylate (PMMA) into the vertebral body using standard vertebroplasty technique. METHODS: Four patients with morbid obesity and symptomatic thoracic disc herniations underwent preoperative vertebroplasty procedures using standard percutaneous techniques. The PMMA cement was used to expeditiously identify thoracic spinal levels of interest using intraoperative fluoroscopy. RESULTS: All 4 patients underwent successful vertebroplasty procedures without complications. The PMMA cement was easily identified intraoperatively and led to the correct identification of the thoracic spinal levels of interest. CONCLUSIONS: Preoperative placement of PMMA into thoracic vertebral bodies using standard vertebroplasty technique provides a safe, efficient, and reliable method of localizing thoracic spine levels intraoperatively. Such procedures can be performed in the outpatient setting and can be associated with extremely low morbidity when done by experienced practitioners. This procedure should be reserved for patients in whom a surgeon anticipates difficulty using standard radiographs or fluoroscopy to localize thoracic spinal levels intraoperatively.

Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia.

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26+/-2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma.

Regional differences in diffusion tensor imaging measurements: assessment of intrarater and interrater variability.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has become a valuable tool in both the research and clinical evaluation of subjects. We sought to quantify interobserver and intraobserver variability of diffusivity and diffusion anisotropy measurements with regard to specific regions of interest (ROIs). MATERIALS AND METHODS: The subject group consisted of 5 healthy control subjects and 7 study subjects (all males; 16-19 years old; mean age = 17.5 years), as part of a protocol for closed head injury. Two whole-brain DTI scans were acquired on a 3T scanner for each subject. Analysis was performed using a ROI approach. Two independent observers analyzed the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) indices in the corpus callosum, cortical spinal tract, internal capsules (ICs), basal ganglia, and centrum semiovale (CSO). Intraobserver and interobserver variability were calculated for the mean ADC, FA, and ordered eigenvalues of the diffusion tensor (lambda(1), lambda(2), and lambda(3)). RESULTS: The overall kappa statistic for intraobserver variability for both observers showed slight-to-substantial agreement (kappa = 0.02-0.69), however FA values in the CSO showed only slight agreement. Interobserver agreement was also slight to substantial for these DTI measurements with high variability in FA values in the IC and CSO. CONCLUSIONS: When one is comparing 2 DTI measurements, it is important to assess intraobserver and interobserver variability. We recommend caution in the analysis of DTI contrasts in the IC and CSO, because we have found the widest range of variability in measurements within these structures.

Comparison of conventional laparoscopic and hand-assisted oncologic segmental colonic resection.

BACKGROUND: Laparoscopically assisted colon resection has evolved to be a viable option for the treatment of colorectal cancer. This study evaluates the efficacy of hand-assisted laparoscopic surgery (HALS) as compared with totally laparoscopic surgery (LAP) for segmental oncologic colon resection with regard to lymph node harvest, operative times, intraoperative blood loss, pedicle length, incision length, and length of hospital stay in an attempt to help delineate the role of each in the treatment of colorectal cancer. METHODS: Patient charts were retrospectively reviewed to acquire data for this evaluation. Between June 2001 and July 2005, 40 patients underwent elective oncologic segmental colon resection (22 HALS and 18 LAP). The main outcome measures included lymph node harvest, operative times, intraoperative blood loss, pedicle length, incision length, and length of hospital stay. RESULTS: The two groups were comparable in terms of demographics. The tumor margins were clear in all the patients. The HALS resection resulted in a significantly higher lymph node yield than the LAP resection (HALS: 16 nodes; range, 5-35 nodes vs LAP: 8 nodes; range, 5-22 nodes; p < 0.05) and significantly shorter operative times (HALS: 120 min; range, 78-181 min vs LAP: 156 min; range, 74-300 min; p < 0.05). Both groups were comparable with regard to length of hospital stay, pedicle length, and intraoperative blood loss. However, the LAP group yielded a significantly smaller incision for specimen extraction (LAP: 7 cm; range, 6-8 cm vs HALS: 5.5 cm; range, 5-7 cm; p < 0.05). CONCLUSION: The findings suggest that hand-assisted laparoscopic oncologic segmental colonic resection is associated with shorter operative times, more lymph nodes harvested, and equivalent hospital stays, pedicle lengths, and intraoperative blood losses as compared with the totally laparoscopic approach. The totally laparoscopic technique was completed with a smaller incision. However, this less than 1 cm reduction in incision length has doubtful clinical significance.

Periaortic hematoma at diaphragmatic crura at helical CT: sign of blunt aortic injury in patients with mediastinal hematoma.

PURPOSE: To evaluate periaortic hematoma (PH) near the level of the diaphragm at abdominal computed tomography (CT) as an indirect sign of acute traumatic aortic injury after blunt trauma in patients with mediastinal hematoma. MATERIALS AND METHODS: From 1998 to 2001, 97 patients with CT evidence of mediastinal hematoma after blunt thoracic trauma were retrospectively identified at two level 1 trauma centers. The presence or absence of PH near the level of the diaphragmatic crura was retrospectively established by a blinded reviewer at each institution. Aortic injury status was determined by reviewing angiographic, surgical, and clinical records. Sensitivity, specificity, positive and negative productive values, and positive and negative likelihood ratios were calculated. RESULTS: Among the 97 patients with mediastinal hematoma, 14 had both PH near the level of the diaphragm and aortic injury; six had aortic injuries without PH, five had PH near the level of the diaphragm without aortic injury, and 72 had no evidence of PH near the diaphragm and no aortic injury. Sensitivity for PH near the level of the diaphragm as a sign of aortic injury was 70%; specificity, 94%; positive predictive value, 74%; and negative predictive value, 92%. The positive likelihood ratio for the presence of aortic injury was 10.8, and the negative likelihood ratio was 0.3. CONCLUSION: PH near the level of the diaphragmatic crura is an insensitive but relatively specific sign for aortic injury after blunt trauma. The presence of this sign at abdominal CT should prompt imaging of the thoracic aorta to evaluate potential thoracic aortic injury.

Municipal hotlines and automated weather stations as a tool for monitoring bad odour dispersion: the northern Negev case.

Bad odours are often dispersed from chemical industries, waste dumps, sewer plants, and other facilities. They are indicative of pollution emissions from these sites and cause discomfort, apprehension, and sometimes signal the presence of health hazards. Monitoring the pollution by direct means, such as chemical analysis of ambient air, is obviously the most reliable mechanism to acquire data regarding pollution. However, this is not always possible. In this paper we report on the value of local government hotlines that record information provided by the public regarding bad odours. These data can alert the authorities to the existence of pollution and should be regarded as potentially useful when collected in conjunction with information from automated weather stations. An analysis of data from the Be'er Sheva municipality and the Ramat Negev regional council hotlines is provided. Complaints recorded by these systems were correlated with weather data from local automatic weather stations to indicate the sources of the bad odours. Wind direction was found to be highly correlated with bad odour and pollution sources, revealing consistent patterns in terms of the time of day and weather conditions.

Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation.

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.

Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas.

We examined the effect of preoperative chemoradiotherapy on the ability to obtain pathologically negative resection margins in patients undergoing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Between 1987 and 2000, 100 patients underwent Whipple resection with curative intent for primary adenocarcinoma of the head of the pancreas. Pathologic assessment of six margins (proximal and distal superior mesenteric artery, proximal and distal superior mesenteric vein, pancreas, retroperitoneum, common bile duct, and hepatic artery) was undertaken by either frozen section (pancreas and common duct) or permanent section. A margin was considered positive if tumor was present less than 1 mm from the inked specimen. Margins noted to be positive on frozen section were resected whenever possible. Of the 100 patients treated, 47 (47%) underwent postoperative radiation and chemotherapy (group I) and 53 (53%) received preoperative chemoradiotherapy (group II) with either 5-fluorouracil (32 patients) or gemcitabine (21 patients). Patient demographics and operative parameters were similar in the two groups, with the exception of preoperative tumor size (CT scan), which was greater in group II (P < 0.001), and number of previous operations, which was greater in group II (P < 0.0001). Statistical analysis of the number of negative surgical margins clear of tumor was performed using Fisher's exact test. All patients (100%) had six margins assessed for microscopic involvement with tumor. In the preoperative therapy group, 5 (7.5%) of 53 patients had more than one positive margin, whereas 21 (44.7%) of 47 patients without preoperative therapy had more than one margin with disease extension (P < 0.001). Additionally, only 11 (25.6%) of the 47 patients without preoperative therapy had six negative margins vs. 27 (50.9%) of 53 in the group receiving preoperative therapy (P = 0.013). Survival analysis reveals a significant increase in survival in margin-negative patients (P = 0.02). Similarly, a strong trend toward improved disease-free and overall survival is seen in patients with a single positive margin vs. multiple margins. Overall, we find a negative impact on survival with an increasing number of positive margins (P = 0.025, hazard ratio 1.3). When stratified for individual margin status, survival was decreased in patients with positive superior mesenteric artery (P = 0.06) and vein (P = 0.04) margins. However, this has not yet resulted in a significant increase in disease-free or overall survival for patients receiving preoperative therapy (P = 0.07).

High prevalence of complement C7 deficiency among healthy blood donors of Moroccan Jewish ancestry.

The incidence of the specific component deficiencies in various ethnic groups is not known, although there appears to be an ethnic predilection for C6 and C8alpha-gamma deficiencies in blacks, whereas C7 and C8beta deficiencies are predominantly noted in Caucasians. Infectious diseases, particularly recurrent meningococcal infections, are observed more commonly with late component deficiencies. In the current study, we have simplified the PCR technique by using site-directed mutagenesis and designer primers in a cohort of Israeli Moroccan Jewish blood donors to ascertain allele frequency in this ethnic group, which, based on earlier studies, was considered to be at risk for C7 deficiency. The total mutant allele frequency in this ethnic cohort was 1.1% of a total of 365 healthy Israeli Moroccan Jews, including one homozygote. The identification of mutant alleles was efficient and inexpensive, and hence a large cohort was studied. The finding of complement deficiency identifies individuals at risk for Neisserial infections, which are known to be potentially life-threatening. Conversely, when a patient of Moroccan ancestry is diagnosed with a Neisserial infection, it is important to determine the complement status.