Sex chromosomes-linked single-gene disorders involved in human infertility

Human infertility is a healthcare problem that has a worldwide impact. Genetic causes of human infertility include chromosomal aneuploidies and rearrangements and single-gene defects. The sex chromosomes (X and Y) are critical players in human fertility since they contain several genes essential for sex determination and reproductive traits for both men and women. This paper provides a review of the most common sex chromosomes-linked single-gene disorders involved in human infertility and their corresponding phenotypes. In addition to the Y-linked SRY gene, which mutations may cause XY gonadal dysgenesis and sex reversal, the deletions of genes present in AZF regions of the Y chromosome (DAZ, RBMY, DBY and USP9Y genes) are implicated in varying degrees of spermatogenic dysfunction. Furthermore, a list of X-linked genes (KAL1, NR0B1, AR, TEX11, FMR1, PGRMC1, BMP15 and POF1 and 2 regions genes (XPNPEP2, POF1B, DACH2, CHM and DIAPH2)) were reported to have critical roles in pubertal and reproductive deficiencies in humans, affecting only men, only women or both sexes. Mutations in these genes may be transmitted to the offspring by a dominant or a recessive inheritance.     

Gingival squamous cell carcinoma: diagnostic delay or rapid invasion?

BACKGROUND: The similarity between gingival squamous cell carcinoma (GSCC) and more common periodontal lesions may lead to a delay in diagnosis or misdiagnosis. Neoplastic lesions of gingival tissues are frequently diagnosed at an advanced stage. METHODS: To assess the relative time from when patients first become aware of the problem to histopathologic diagnosis (total diagnostic time), 59 consecutive oral cancer cases were examined in this study. The following variables were considered: age, gender, smoking habits, tumor stage at diagnosis, and total diagnostic time. The median of the patients' total diagnostic time (1.5 months) was used as a cutoff point to distinguish between delayed and non-delayed cases. Analysis of the variables was undertaken using the Student t test and chi2 test, with a 95% confidence interval (CI). RESULTS: The total diagnostic time was <1.5 months for 75% of gingival carcinomas, 50% of tongue carcinomas, and 78% of floor-of-the-mouth carcinomas. It was >1.5 months for 25% of gingival carcinomas, 50% of tongue carcinomas, and 21% of floor-of-the-mouth carcinomas. No significant differences in time before diagnosis were found when gingival cancers were compared to other oral tumors (chi2=0.21; 95% CI=-0.40 to 0.26). However, by the time of diagnosis, gingival cancers had invaded adjacent structures more frequently than other oral cancers (chi2=13.51; 95% CI=0.18 to 0.85). CONCLUSIONS: The gingival location of oral squamous cell carcinoma (OSCC) was associated with advanced stages at the time of diagnosis, due to early invasion of contiguous bone tissue (T4-primary tumor). This would indicate that even earlier referral and diagnosis are necessary.     

The Brazilian Founder Mutation TP53 p.R337H is Uncommon in Portuguese Women Diagnosed with Breast Cancer

Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern Brazil, there has been controversy on its origin. Preliminary analysis of a small subset of Brazilian mutation carriers revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families, from Portugal and Germany. Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer (BC) in Southern Brazil are p.R337H carriers, we analyzed p.R337H in a Portuguese cohort of women diagnosed with this disease. Median age at diagnosis among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study including 815 BC‐affected women from Brazil, in which carrier frequencies of 12.1 and 5.1% in pre‐ and postmenopausal women were observed, respectively. These findings suggest that the Brazilian founder mutation p.R337H, the most frequent germline TP53 mutation reported to date, is not a common germline alteration in Portuguese women diagnosed with BC.     

Incisional negative pressure wound therapy does not reduce surgical site infections in abdominal midline incisions: a case control study

Abstract

Purpose: There is evidence from various surgical specialties that incisional negative pressure wound therapy (iNPWT) might reduce postoperative surgical site infections (SSIs). In visceral and general surgery, there is varying evidence of its efficacy in reducing surgical site infections.

Methods: A prospectively registered patient cohort of 43 patients with abdominal wall and visceral surgery received treatment with iNPWT and was compared to a matched retrospective cohort to analyze its effects on SSI occurrence and respective risk factors. Groups were matched by procedure, sex, body mass index and age. We used two different systems of iNPWT: (i) PREVENA^TM or (ii) self-made epicutaneous iNPWT from common VAC material.

Results: We could not find a total reduction in postoperative SSIs by application of iNPWT. But within the iNPWT cohort, patients with self-made iNPWT suffered more often from SSIs compared to the commercial iNPWT subgroup. No patient specific risk factors could be identified to advocate the use of iNPWT.

Conclusion: Our data do not support the use of an incisional negative pressure wound therapy on closed wounds in midline laparotomy incisions. Although, differences exist between the commmercial and self-made systems.     

Predictive factors associated with complete pathological response after neoadjuvant treatment for rectal cancer

PurposeA proportion of 10 to 30% of patients treated by chemoradiotherapy followed by total mesorectal excision surgery for a locally advanced rectal cancer can achieve a complete pathological response. We aimed to identify predictive factors associated with complete pathological response or no response and to assess the impact of each response on survival rates.Patients and methodsPatients treated with long course chemoradiotherapy for locally advanced and/or node positive rectal cancer from 2010 to 2016 were retrospectively reviewed. Statistical analysis was carried out to determine predictors of tumor regression and treatment outcomes.ResultsRecords were available on 70 patients. In the univariate analysis, clinical factors associated with complete tumor response were tumor mobility in digital rectal examination (P = 0.047), a limited parietal invasion (P = 0.001), clinically negative lymph node (P < 0.001) and a circumferential extent greater than 50% (P = 0.001). On the other hand, a T4 classification and an endoscopic tumor size greater than 6 cm were associated with no response to treatment (P = 0.049 and P = 0.017 respectively). On multivariate analysis, T2 clinical classification and N0 statement before treatment were independent predictive factors of pathologic complete response (P < 0.001 and P = 0.001) and a delayed surgery after 12 weeks was associated with no response to treatment (P = 0.001).ConclusionThe identification of predictive factors of histological response may help clinicians to predict the prognosis and to propose organ preservation for good responders.