Advanced molecular approaches in male infertility diagnosis†.

In the recent years a special attention has been given to a major health concern namely to male infertility, defined as the inability to conceive after 12 months of regular unprotected sexual intercourse, taken into account the statistics that highlight that sperm counts have dropped by 50-60% in recent decades. According to the WHO, infertility affects approximately 9% of couples globally, and the male factor is believed to be present in roughly 50% of cases, with exclusive responsibility in 30%. The aim of this article is to present an evidence-based approach for diagnosing male infertility that includes finding new solutions for diagnosis and critical outcomes, retrieving up-to-date studies and existing guidelines. The diverse factors that induce male infertility generated in a vast amount of data that needed to be analyzed by a clinician before a decision could be made for each individual. Modern medicine faces numerous obstacles as a result of the massive amount of data generated by the molecular biology discipline. To address complex clinical problems, vast data must be collected, analyzed, and used, which can be very challenging. The use of artificial intelligence (AI) methods to create a decision support system can help predict the diagnosis and guide treatment for infertile men, based on analysis of different data as environmental and lifestyle, clinical (sperm count, morphology, hormone testing, karyotype, etc.), and "omics" bigdata. Ultimately, the development of AI algorithms will assist clinicians in formulating diagnosis, making treatment decisions, and predicting outcomes for assisted reproduction techniques.

Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

Plasma CXCL10 correlates with HAND in HIV-infected women.

HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV-infected (HIV+) young adults, parenterally infected during early childhood. One hundred forty-four HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1ß, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared with neurocognitive outcomes, and the influence of sex and HIV disease biomarkers was assessed. In this cohort of young adults (median age of 24 years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479 cells/mm3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma, controlling for sex, higher levels of IL-6 and TNF-α were associated with NCI (p < 0.05). Plasma CXCL10 showed a significant interaction with sex (p = 0.02); higher values were associated with NCI in women only (p = 0.02). Individuals with undetectable viral load had significantly lower plasma CXCL10 (p < 0.001) and CCL2 (p = 0.02) levels, and CSF CXCL10 (p = 0.01), IL-6 (p = 0.04), and TNF-α (p = 0.04) levels. NCI in young men and women living with HIV was associated with higher IL-6 and TNF-α in plasma, but not in the CSF. CXCL10 was identified as a biomarker of NCI specifically in women with chronic HIV infection.

[Radiofrequency ablation for liver metastases--mini invasive therapeutic option for patients with unresecable tumors]. / Distructia prin radiofrecventa a metastazelor hepatice--optiune terapeutica miniinvazia optimala la pacientii non-rezecabili chirurgical.

UNLABELLED: Radiofrequency ablations (RFA), a new therapeutic option for liver metastases, proceeded by open surgery or laparoscopic approach, provide an acceptable control of local tumor process, involved lower risks than resection surgery. OBJECTIVES: We analyzed this procedure, for classic indication in hepatic metastatic tumors, based on four years experience, focused on perioperative complications, recurrence rate and long distant evolution. METHOD: Between December 2006 and December 2010, 61 patients with liver metastases underwent RFA; 46 cases had metastatic lesions from colo-rectal cancer, 9 cases from breast cancer, 4 cases from gastric cancer and 2 cases from ovarian cancer. RFA was performed in 55 patients via open surgery and laparoscopic approach in 6 patients. Postoperative course was followed with CT scan at 1 month, and then at 3 month interval, in correlation with tumor markers level. RESULTS: Perioperative complications occurred in 8 cases, consist of prolonged fever, severe hepatic cytolysis, without other complications such, biliary tract injury, hemorrhage, and peritonitis; no mortality caused by RFA procedure. 10 cases had local recurrence, at 6 and 25 month after post RFA procedure. CONCLUSIONS: Initial experience shows that RFA is a safe procedure for treatment of liver metastases, with low rate of morbidity and local recurrence, indicated for patients with unresecable lesions or high risks for surgical resection.

May inflammatory markers be used for monitoring the continuous positive airway pressure effect in patients with obstructive sleep apnea and arrhythmias?

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is defined by recurrent episodes of significant reduction or absence of the oro-nasal airflow during sleep, in the presence of thorax and abdominal movements and snoring. The pathophysiological consequences of intermittent hypoxia determined by OSAS are represented by systemic inflammation, the release of free oxygen radicals and activation of the sympathetic nervous system. Cardiac arrhythmias are a frequent comorbidity in patients with OSAS. HYPOTHESIS: We hypothesized that the continuous positive airway pressure (CPAP) therapy has an effect on inflammatory markers (erythrocyte sedimentation rate, fibrinogen, and red cell distribution width) in patients with OSAS and cardiac arrhythmias. EVALUATION OF THE HYPOTHESIS: We tested this hypothesis on 52 patients diagnosed with OSAS and cardiac arrhythmias, divided into two groups: group A (patients who received CPAP therapy and pharmacological therapy) and group B (only pharmacological therapy). The patients were evaluated at enrollment (T0), at 3 and 6 months. We did not find a statistically significant difference of erythrocyte sedimentation rate (ESR) and fibrinogen levels between the two groups. Regarding the red cell distribution width (RDW), the CPAP treatment seems to have improved the RDW values in patients who received this treatment. Also, in patients from group A, a significant decrease in the average heart rate was noticed after 3 months. CONSEQUENCES: Fibrinogen and ESR cannot be used for monitoring the CPAP therapy in patients with OSAS and arrhythmias. Instead, the beneficial effect of CPAP in patients with OSAS and cardiac arrhythmias can be monitored with the help of the RDW, which could also be used for evaluating the cardiovascular risk in patients with OSAS and arrhythmias.

Determination of the strong coupling constant α s ( m Z ) in next-to-next-to-leading order QCD using H1 jet cross section measurements: H1 Collaboration.

The strong coupling constant α s is determined from inclusive jet and dijet cross sections in neutral-current deep-inelastic ep scattering (DIS) measured at HERA by the H1 collaboration using next-to-next-to-leading order (NNLO) QCD predictions. The dependence of the NNLO predictions and of the resulting value of α s ( m Z ) at the Z-boson mass m Z are studied as a function of the choice of the renormalisation and factorisation scales. Using inclusive jet and dijet data together, the strong coupling constant is determined to be α s ( m Z ) = 0.1157 ( 20 ) exp ( 29 ) th . Complementary, α s ( m Z ) is determined together with parton distribution functions of the proton (PDFs) from jet and inclusive DIS data measured by the H1 experiment. The value α s ( m Z ) = 0.1142 ( 28 ) tot obtained is consistent with the determination from jet data alone. The impact of the jet data on the PDFs is studied. The running of the strong coupling is tested at different values of the renormalisation scale and the results are found to be in agreement with expectations.

[A rare complication of colostomy]. / Complicatie rara a unei colostomii.

A case of a 64 years old female patient who had had a Miles operation 6 years ago for rectal cancer and at the present hospital admission she came in with a severe infection around her left colostomy. Initially, she presented a quite localized peristomal infection but, subsequently, the infection has evolved to an extensive necrotizing fasciitis of the abdomen, a large dehiscence of colostomy and severe sepsis. Repeated surgery and transverse colostomy, to put at rest infected left colostomy, plus aggressive medical treatment resulted in a good recovery, with the wounds healing and redo of the left colostomy. Now she is on the waiting list to get rid of the transverse colostomy.

[Platypnea-orthodeoxia syndrome: A case of hypoxemia associated with a patent foramen ovale]. / Platypnée-orthodéoxie: un cas rare d'hypoxémie secondaire d'une réouverture post-traumatique du foramen ovale perméable.

Platypnea-orthodeoxia syndrome is a rare disease characterized by dyspnea and oxygen desaturation in the upright position with improvement in the supine position. We report a case of an 87-year-old woman with a recent history of traumatic hip, spine deformity and vertebral compression fracture, referred due to dyspnea oxygen desaturation. Thoracic tomodensitometry excluded the diagnosis of pulmonary embolism. Transthoracic echocardiography, with intravenous administration of agitated saline contrast solution, revealed the presence of atrial septal defect associated with a right to left shunting and mild enlargement of aortic root. Surgical closure of atrial septal defect resulted in resolution of the syndrome.

MANAGEMENT OF TRAUMATIC LIVER LESIONS.

AIM: To determine the correct therapeutic approach to the different grades of liver trauma. MATERIAL AND METHODS: The study is based on a retrospective analysis of treatment outcomes in 56 patients with abdominal trauma admitted over a 9-year period to in the IIIrd Surgical Clinic of the Iasi "Sf. Spiridon" Hospital. It is focused on operative or non-operative management of liver trauma, surgical technique used, morbidity and postoperative mortality. Data were collected from electronic medical records and observation sheets and processed and interpreted using Microsoft Excel statistical functions. RESULTS: In the interval May 26, 2005-April 19, 2013 56 cases of abdominal trauma were recorded, 31 (55.35%) residing in urban areas, and 25 (44.64%) in rural areas. The mean age was 39 years, range 18-83 years old. The male/female ratio was 2.5/1 and the group consisted of 40 (71.42%) male patients and 16 (28.57%) female patients. The causes of abdominal trauma were: car accident in 29 (51%) cases, fall from different heights in 6 (10%) patients, workplace-related accidents in 8 patients (14%) and direct hit injury in 12 patients (12%). In our cohort, 51 (91%) patients with abdominal trauma have been emergency admitted, 3 patients (5%) were transferred from different medical units, and 2 patients (4%) were referred by a specialist doctor. Two or more simultaneous lesions were diagnosed in 53 (96%) cases. Of the 45 patients with traumatic liver injuries diagnosed on admission, 32 (71%) required surgical intervention. In the remaining 13 (29%) patients, the therapeutic management was conservative. CONCLUSIONS: Hepatic traumas are often severe, and frequently associated with multiple injuries. The non-operative management is indicated in liver lesions grade I, II and III according to the American Association for the Surgery of Trauma (AAST), if abdominal cavity organs are not injured. Higher grade liver lesions (over IV) in which the hemorrhagic risk persists or reappears require surgical intervention as soon as possible, and according to the type of lesion, the right procedure should be chosen.

Pain-associated biomarkers in breast cancer.

Breast cancer represents a major public health problem, being the highest incidence neoplasia in females in Romania. The most important step in the treatment of this neoplasia is the surgical procedure; the biggest problem associated with this form of treatment in these patients is pain-related. Pain is a complex symptom with an impact on quality of life and psychology of cancer patient and can only be monitored verbally and subjectively. Consequently, the purpose of our work is to identify some biochemical parameters involved in the events cascade associated with inflammation and pain in breast cancer female patients, monitored in dynamics of anesthesia and surgical procedure. Measurements of lipid peroxides, ceruloplasmin and immune circulating complexes in mentioned dynamics have been performed. The recorded values are in concordance with the inflammatory processes and pain intensity, thus we can allege that these measurements can complete the pain-associated clinical picture in female breast cancer patients.

NONALCOHOLIC FATTY LIVER DISEASE AND ITS COMPLICATIONS--ASSESSING THE POPULATION AT RISK. A SMALL SERIES REPORT AND LITERATURE REVIEW.

UNLABELLED: The aim of the study was to highlight correlations between serum biochemical markers and different degrees of liver inflammation or fibrosis revealed by liver biopsy in morbidly obese patients. We also wanted to emphasize that the occurrence of hepatocellular carcinoma (HCC) is increasingly associated with obesity, metabolic syndrome and nonalcoholic fatty liver disease. MATERIAL AND METHODS: A clinical retrospective study was carried out on a series of 13 patients operated for morbid obesity in our surgical unit. Included in this study were only the obese patients referred for bariatric surgery without other risk factors for liver disease and in whom a liver biopsy was taken during metabolic surgery. RESULTS: The pathology report revealed different stages of nonalcoholic fatty liver disease in all 13 patients: pathological features of steatohepatitis (7 patients), hepatic steatosis (5 patients) and lesions specific for evolving cirrhosis (1 patient). Regardless of the pathological changes of the liver, except the patient with evolving cirrhosis, none of these patients showed changes in classical liver function blood tests. DISCUSSIONS: Hepatic alteration in obese patients, ranging from simple steatosis to steatohepatitis or even cirrhosis, is not always correlated with the values of classical biological liver function tests. Literature data suggest the involvement of adipokines in the development and progression of steatosis as the hepatic expression of metabolic and chronic inflammation syndrome occurring in obese patients. Furthermore, these proteins secreted by adipose tissue seem to be related to the HCC occurrence. However, none of these studies show the exact pathway followed by the hepatic cell from simple fatty liver to hepatocellular carcinoma. CONCLUSIONS: finding and selecting the population at risk for fatty liver disease progression and for HCC development among obese patients is mandatory.

Spectral and interferometrical study of the interaction of haemin with glutathione.

The interaction of haemin with reduced glutathione (GSH) was investigated in vitro and the association constant was determined by both spectrophotometric and interferometric methods. In order to elucidate the nature of this interaction, the reaction of haemin with a typical reductive agent (sodium dithionite) and a typical chelating agent for hem-iron (histidine) was also studied. Haemin-induced haemolysis in the presence and absence of GSH was monitored spectrophotometrically. The results outline the role of GSH at physiological concentration in preventing erythrocyte damage by haemin.

Combined modality treatment for locally advanced breast cancer.

PURPOSE: To assess the value of aggressive loco-regional surgery in desperate situations with locally advanced breast cancer. METHODS: In this study there were considered 31 patients with locally advanced breast cancer who underwent surgery in a 5-year period. 10 of them received 3 cycles of chemotherapy and radiotherapy before surgical intervention; the rest of the 21 patients had systemic or local contra-indications for neo-adjuvant therapy. We describe clinical aspects and technical difficulties. Surgical intervention focused on tumour removal and lymph node dissection. Skin defect was covered with flaps according to the Mortimer-Show technique. Postoperatively, the outcome was influenced in a favourable way by the use of Detralex, a micronized flavonoid; all but 2 patients received chemotherapy and locoregional radiotherapy. RESULTS: 25 patients survived free of disease; from 6 patients who suffered recurrence, 2 are still living and 4 have died. CONCLUSIONS: In some forms of locally advanced breast cancer, aggressive surgery offers improvement in the quality of life and increases survival.

Low p27(Kip1)expression is associated with poor prognostic factors in breast carcinomas.

PURPOSE: This study was designed to detect the presence of the p27(Kip1) protein expression in breast carcinomas and corresponding axillary lymph node metastases, as well as any potential correlation of p27(Kip1) with factors of tumor progression and prognosis (estrogen receptors-ER, progesterone receptors-PR, c-erbB-2, p53). PATIENTS AND METHODS: 44 primary breast cancers and positive axillary lymph nodes from 24 cases were examined by immunohistochemistry. RESULTS: 19 out of 44 (43.18%) tumor specimens expressed the p27 protein, whereas 25 (56.82%) specimens expressed it only at low levels or were negative. Absence of p27 correlated significantly (p < 0.05) with a negative status for ER and PR receptors. The presence of p27 protein in primary tumors was always associated with positive expression in the corresponding nodal metastases. CONCLUSION: Our results indicate a correlation between lack or low levels of p27 protein expression and the absence of hormone receptors. The p27 phenotype is preserved from the primary breast tumors to the corresponding axillary lymph node metastases.

Sequential phenotype changes in progressive lesions of breast carcinoma.

Malignant transformation is the result of genetic events, translated into sequential acquisitions of multiple abnormalities in the control of cellular growth and cell cycle regulation. We determined the expression of the estrogen receptor (ER), progesterone receptor (PR), c-erbB-2 and p53 gene products in a patient with mixed (ductal and lobular) invasive breast carcinoma bearing different coexisting lesions. The purpose of the study was to establish a possible correlation between the expression pattern for these molecules and the histological appearance of the breast tumor. Our results showed no positivity for ER. PR expression was restricted to normal epithelium, simple hyperplasia and in situ carcinoma. c-erbB-2 was detected in all lesions with the exception of normal epithelium and immunostaining for p53 was found positive only in in situ and invasive carcinoma. These findings support the hypothesis of tumorigenesis as a multistep process and as a sum of changes, each representing an advantageous acquisition for the malignant cells' behavior. The loss of hormone receptors' expression occurred as an early event in this case, while the p53 mutations were found only in more advanced neoplastic lesions.

[Surgical treatment of hepatocellular carcinoma--indications, limitations, realities]. / Tratamentul chirurgical al carcinomului hepato-celular--indicatii, limite, exigente actuale.

The present study analyzes the importance of the factors in improving the resectability, obtaining morbidity and mortality rates in accordance to the actual exigencies. In The III-rd Surgical Clinic, "Sf.Spiridon" Hospital, Iasi, during 1998-2003, 24 cases of CHC (19 men, 5 women with a median age of 58.5 years), usually developed on a cirrhotic liver, benefited by surgical approach. The tumoral mass (median size 7.8 cm) was situated in the left liver (15 cases--62.5%), right liver--13 cases and for 1 case with multiple localization (the segments VI-VII and III). For 12 cases (50%) various extensions of liver resections have been undergone: left lobectomies II-III--4 cases, left hepatectomy--1 case, segmentectomies VI--3 cases, segmentectomy III + bisegmentectomy VI-III--1 case, atypical hepatectomy--3 cases. Only 2 cases benefited by right portal vein ligation prior to resection. In 12 cases intraoperative exploration and US examination (4 cases) contraindicated the resection. One patient deceased on the entire lot (4.16%); post-resection mortality--8.33%. In conclusion, the early diagnostic of CHC developed on cirrhotic liver, the patients selection, the use of laparoscopy and intraoperative US, the available devices (CUSA dissector), selective ligation of portal branch prior to resection represents imperative elements in improving the resectability in safe conditions for the patient.

[Surgical initial attitude in epithelial ovarian advanced cancer]. / Conduita chirurgicala în cancerul ovarian epitelial avansat.

UNLABELLED: The purpose of this work is to show the value of aggressive excisional surgery in epithelial ovarian advanced cancer (COEA). MATERIAL AND METHOD: Between May 1993-May 1997, there were 103 obs. with ovarian diseases; 28 obs. (27.1%) with COEA and 75 obs. (72.9%) with benign diseases. All the patients had a subtotal hysterectomy with bilateral anexectomy and omentectomy. The operation was extended to other anatomic elements; in the case of 4 obs., we practiced a segmentary resection of left colon, 2 obs. had an anterior resection of the rectum and a partial resection of the pelvic peritoneum, 15 obs. suffered an excision of tumoral masses from the gastro colic omentum and the right parietocolic space and 7 obs. had a resection of pelvic peritoneum and of the right parietocolic space peritoneum. The optimal cytoreduction with a tumoral residuum less than 2 cm was realized for 23 obs. (82.14%) and for 5 obs., the tumoral residuum was greater than 2 cm (17.76%). The medium survival of the patients with a tumoral residuum inferior to 2 cm was 41 months, at 4 years 54% of the observations being alive, compared to only 14 months for the patients with tumoral residuum superior to 2 cm, at 4 years the survival being only of 15%. All the observations have beneficiated of chemotherapy. The disease reappeared for 23 obs. after a variable period of time. It's treatment consisted of: surgery followed by chemotherapy for 18 obs. and chemotherapy of second line alone for 5 obs. CONCLUSIONS: The ovarian epithelial cancers, famous for an intermediary answer to chemotherapy, lead to an aggressive surgical management with partial extra genital organ sacrifices, to offer a chance of life.

[Surgical treatment of locally advanced esophago-gastric cancer; preliminary results]. / Tratamentul chirurgical al cancerelor jonctiunii eso-gastrice local avansate; rezultate preliminare.

UNLABELLED: The aim of this paper is to sustain the palliative resection in neoplasm of the esophago-gastric junction, as a surgical approach that allows a better post-operative life comfort in comparison with simple gastrostomy. 62 observations with proximal neoplasm of the stomach (12.5%) were identified between January 1996-August 2001, representing 12.5% of the 496 patients with gastric neoplasm admitted in our unit in the same period. Out of these 62 cases, 55 (88.71%) underwent surgical procedures. Our attitude was aggressive in 25 cases. 40.32%, including the locally advanced lesions with palliative surgical indications (18 obs.). The other 30 patients underwent: 10 laparotomies, 5 gastrostomies and 15 jejunostomies. Local invasion to the neighboring organs imposed partial resection of the transverse colon--1 obs., of the transverse mesocolon--2 obs., and corporeo-caudal pancreatectomies--3 obs. The surgical approach was a left abdomino-thoracic incision, with total gastrectomy and distal esophagectomy, with N1 and N2 lymphadenectomy, splenectomy, and esojejunal intrathoracic anastomosis, with a Roux-en-Y loop, with or without jejunostomy (13 obs.). The immediate post-operative complications were 8 anastomotic leakage, one duodenal stump fistula, one occlusion due to a jejunostoma, and 13 extradigestive complications. There were 5 post-operative deaths. CONCLUSION: Neoplasm of the esophago-gastric junction is lately diagnosed, but whenever is possible, total gastrectomy with distal esophagectomy should be carried out.

[Synchronous colonic cancers]. / Cancerele sincrone ale colonului.

UNLABELLED: The aim of this study is to present the difficulty of an accurate preoperative diagnostic for synchronous colonic cancers and to sustain the necessity of total colectomy. A retrospective study was carried out on 16 patients hospitalized in the IIIrd Surgical Unit, St. Spiridon Hospital, U.M.Ph. "Gr.T.Popa" Iasi between 1990-1999. The surgical procedures were: extensive colectomy with ileo-sigmoid anastomosis, segmentary colectomy, total colectomy with ileo-rectal anastomosis. RESULTS: Perioperative mortality: zero; uneventfully recovery for all patients. A metachronous lesion 3 years after the first operation was detected in one patient; postoperatively, one patient developed occlussion 3 months after, requiring re-operation. CONCLUSIONS: 1. synchronous colonic cancers are closely related with a genetic instability of the colonic mucosa; 2. total colectomy is a safe manner to prevent metachronous lesions.

Split-thickness skin grafting in oncologic surgery of the limb--a case report.

Large excision of tumor soft tissues is often complicated by infections, seriously undermined blood supply and venous drainage, tendon exposure, functional impairment. We report the case of a 67 years old woman admitted for a sarcoma of the right forearm occurring 14 years after a modified radical mastectomy and adjuvant chemotherapy for carcinoma of the right breast. A wide excision of the lesion and split-thickness skin graft was performed with uneventful recovery and satisfactory healing of the graft tissue and functional aspect of the arm. In the last few decades, there has been a search for solutions in tissue repair without need for auto grafts, such as biological substitutes that could repair or improve the function of tissue. In case none of these products are available, auto graft is a good choice and it may be commonly used in the surgical treatment of postoperative soft tissues defects after oncologic surgery.