Individual red blood cell fetal hemoglobin quantification allows to determine protective thresholds in sickle cell disease

Polymerization of the sickle hemoglobin (HbS) is a key determinant of sickle cell disease (SCD), an inherited blood disorder. Fetal hemoglobin (HbF) is a major modulator of the disease severity by both decreasing HbS intracellular concentration and inhibiting its polymerization. However, heterocellular distribution of HbF is common in SCD. For HbS polymerization inhibition, the hypothesis of an “HbF per red blood cell (HbF/RBC) threshold” requires accurate measurement of HbF in individual RBC. To date, HbF detection methods are limited to a qualitative measurement of RBC populations containing HbF - the F cells, which are variable. We developed an accurate method for HbF quantification in individual RBC. A linear association between mean HbF content and mean RBC fluorescence by flow cytometry, using an anti-Human-HbF antibody, was obtained from non-SCD subjects presenting homogeneous HbF distribution. This correlation was then used to measure HbF/RBC. Hydroxyurea (HU) improves SCD clinical manifestations, mainly through its ability to induce HbF synthesis. The HbF distribution was analyzed in 14 SCD patients before and during HU treatment. A significant decrease in RBC population containing less than 2 pg of HbF/RBC was observed. Therefore, we tested associations for %RBC above different HbF/RBC thresholds and showed a decrease in the pathognomonic vaso-occlusive crisis incidence from the threshold of 4 pg. This quantity was also correlated with the level of sickle RBC after in vitro deoxygenation. This new method allows the comparison of HbF/RBC distributions and could be a useful tool to characterize baseline patients HbF distribution and therapeutic response to HbF inducers.     

Identifying causes for high readmission rates after stoma reversal

Background

Unplanned readmissions after colorectal surgery impact patient and financial outcomes. Our goal was to identify factors related to readmission in ostomy reversal patients.

Methods

Review of a prospective department database was performed from 2006 to 2012 to identify patients who underwent an ostomy reversal. Patients were stratified into nonreadmitted and readmitted within 30 days of ostomy reversal. The main outcome measures were predictors of readmission and characteristics of patients readmitted and not readmitted.

Results

A total of 351 ostomy reversals (86 % ileostomy and 14 % colostomy) were analyzed; 44 patients were readmitted (12.5 %). Readmitted and nonreadmitted patients were similar in age, body mass index, gender, comorbidities, indications for the index operation, and time to ostomy reversal. Readmitted patients had longer operative times (p = 0.002) and length of stay (p = 0.001), more intraoperative blood loss (p = 0.003), intraoperative complications (p = 0.005), ICU requirements (p < 0.0001), need for temporary nursing at discharge (p < 0.001), and higher total hospital costs than nonreadmitted patients (p = 0.0162). Longer operative time [odds ratio (OR) 1.006, 95 % confidence interval (CI) 1.001–1.012], intraoperative complications (OR 7.334, 95 % CI 1.23–43.761), ICU stay (OR 1.291, 95 % CI 1.18–1.893), delayed discharge (OR 1.085, 95 % CI 1.003–1.173), and discharge to skilled nursing facility (OR 6.936, 95 % CI 1.531–31.332) were independent predictors of readmission. Ostomy type had no independent effect on readmission.

Conclusions

Differences in perioperative and outcomes variables exist between readmitted and nonreadmitted patients after ostomy reversal. Longer operative times, intraoperative complications, intensive care unit care, longer length of stay, and skilled nursing at discharge were independently predictive of readmission. These findings can be used to identify high-risk patients prospectively, potentially improving clinical outcomes and healthcare utilization.     

Malpractice awareness among surgeons at a teaching hospital in Pakistan

Background

The duty of a doctor to take care presumes the person who offers medical advice and treatment to unequivocally possess the skills and knowledge to do so. However, a sense of responsibility cannot be guaranteed in the absence of accountability, which in turn requires a comprehensive medical law system to be in place. Such a system is almost non-existent in Pakistan. Keeping the above in mind, we designed this study to assess the knowledge, attitudes and practices of surgeons regarding malpractice at a tertiary care center in Pakistan.

Methods

This was an observational, cross-sectional, questionnaire-based study conducted during a three month period from 31st March, 2012 to 30th June, 2012 at Civil Hospital, Karachi. Surgeons who were available during the period of our study and had been working in the hospital for at least 6 months were included. Self-administered questionnaires were distributed after seeking informed, written consent. The specialties included were general surgery, cardiothoracic surgery, neurosurgery, ophthalmology, otolaryngology, plastic surgery, pediatric surgery, orthopedic surgery, oral and maxillofacial surgery and gynecology and obstetrics. The study questionnaire comprised of four sections. The first section was concerned with the demographics of the surgeons. The second section analyzed the knowledge of the respondents regarding professional negligence and malpractice. The third section assessed the attitudes surgeons with regard to malpractice. The last section dealt with the general and specific practices and experiences of surgeons regarding malpractice.

Results

Of the 319 surgeons interviewed, 68.7% were oblivious of the complete definition of malpractice. Leaving foreign objects inside the patient (79.6%) was the most commonly agreed upon form of malpractice, whereas failure to break news in entirety (43.9%) was most frequently disagreed. In the event of a medical error, majority (67.7%) were ready to disclose their error to the patient. The most common perceived reason for not disclosing the error was threat of a claim or assault (90.9%). Majority (68.3%) believed that malpractice had a negative effect on reputation. Only 13(4.1%) had received at least one legal claim for damages. Only about three-fourths (75.5%) had the habit of frequently obtaining informed consent from the patients. 83(26.0%) expressed reluctance in accepting a case that was deemed to be difficult. Financial gains and liabilities were responsible for biased approach in 8.5% and 12.2% of the respondents respectively.

Conclusion

There is a dire need of programs aimed at increasing awareness among practicing surgeons in our setup. Proactive measures are required for the formulation of an efficient system of litigation. Physician accountability will not only arouse a greater sense of responsibility in them, but will also augment the confidence placed by patients on the healthcare system.     

Non-structural protein NS4B: HCV replication web inducer

Hepatitis C virus (HCV) genome consists of a positive strand RNA encoding a polyprotein, having 3 structural and 6 non-structural components including non structural protein 4B (NS4B). NS4B is a 27 KDa protein, of 261 amino acids, released after polyprotein cleavage by NS3 serine protease and localized on endoplasmic reticulum (ER). NS4B has 2 alpha helices each in its N and C terminal domains and 4 transmembrane domains in its central region. N-terminal domain resides in the ER-lumen while C-terminal domain resides in the cytoplasm. Around its middle it has a nucleotide binding motif (NBM) which plays a role in ATP and GTP hydrolysis. It is involved in hyperphosphorylation of the NS5A protein and is also thought to be involved in production of various cytokines by the activation of NF-kB pathway. NS4B plays a major role in HCV replication by inducing membranous web and facilitating other HCV proteins necessary for replication. Here we discuss various functional aspects of this protein and their potential for targeted antiviral approaches.     

Accuracy of 64-slice multidetector computed tomography scan in detection of the point of transition of small bowel obstruction

Purpose  

To determine the accuracy of 64-slice multidetector computed tomography scans in detecting the point of transition of small bowel obstruction by using surgical findings as the gold standard.     

Sperm retrieval rate and reproductive outcome of infertile men with azoospermia factor c deletion

To evaluate the success rate in sperm retrieval (SR) through microdissection testicular sperm extraction (micro‐TESE) in infertile azoospermia factor c (AZFc)‐deleted men and determining their reproductive outcomes following ICSI, medical records of couples with AZFc‐deleted male partners were reviewed on patient's age, serum hormone levels, karyotype, testicular pathology and pregnancy outcomes. A comparison on age and serum hormone level was conducted between groups with positive and negative sperm retrieval in both azoospermic and oligozoospermic AZFc‐deleted men. Of 225 who had AZFc deletion, 195 cases followed clinical treatments. From 195 cases, 116 were azoospermic, 79 were oligozoospermic. Pathology profile was available in 103 of 195 subjects which the predominant trait was SCOS and was seen in 66.9% of cases (69 of 103). Success rate of sperm retrieval in azoospermic patients who underwent micro‐TESE was 36.3% (28/77). Forty‐three oligozoospermic and 17 azoospermic patients started ART cycle. Pregnancy rate in oligozoospermic group was 35.4% (17 cases), whilst there was no clinical pregnancy in azoospermic group. In conclusion, the pregnancy and delivery in oligozoospermic patients with AZFc deletion are comparable with other studies, but despite of sperm retrieval in azoospermic patients with AZFc deletion, the chance of pregnancy or delivery in these patients was very low.