Use of NOACS in high-risk patients with atrial fibrillation in Saudi Arabia: Perspectives on improving patient care.

BACKGROUND: Despite the widespread and increasing use of NOACs in Saudi Arabia, there is a lack of contemporary guidance specific to the region. In particular, guidance on NOAC use in high-risk patients who are more likely to experience bleeding with oral anticoagulant therapy is needed. There is an unmet need for a review of contemporary evidence coupled with expert insights on safe and effective NOAC use in high-risk patients with AF in Saudi Arabia. RESEARCH DESIGN AND METHODS: This article provides a detailed review of contemporary literature on NOAC use in high-risk patients with AF. Additionally, key gaps in the literature are identified and expert insights are shared to guide effective management of patients and the significance of local data is evaluated with respect to challenges in optimizing the use of NOACs. CONCLUSIONS: This article provides information that complements and expands on existing reviews and guidelines on NOAC use in patients with AF, with a focus on challenges specific to the Saudi Arabian context with the potential to make a positive contribution to the medical community in Saudi Arabia and in other nations.

Glucose-6-phosphate dehydrogenase inhibition attenuates acute lung injury through reduction in NADPH oxidase-derived reactive oxygen species.

Acute lung injury (ALI) is a heterogeneous disease with the hallmarks of alveolar capillary membrane injury, increased pulmonary oedema and pulmonary inflammation. The most common direct aetiological factor for ALI is usually parenchymal lung infection or haemorrhage. Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) are thought to play an important role in the pathophysiology of ALI. Glucose-6-phosphate dehydrogenase (G6PD) plays an important role both in production of ROS as well as their removal through the supply of NADPH. However, how G6PD modulation affects NOX2-mediated ROS in the airway epithelial cells (AECs) during acute lung injury has not been explored previously. Therefore, we investigated the effect of G6PD inhibitor, 6-aminonicotinamide on G6PD activity, NOX2 expression, ROS production and enzymatic anti-oxidants in AECs in a mouse model of ALI induced by lipopolysaccharide (LPS). ALI led to increased G6PD activity in the AECs with concomitant elevation of NOX2, ROS, SOD1 and nitrotyrosine. G6PD inhibitor led to reduction of LPS-induced airway inflammation, bronchoalveolar lavage fluid protein concentration as well as NOX2-derived ROS and subsequent oxidative stress. Conversely, ALI led to decreased glutathione reductase activity in AECs, which was normalized by G6PD inhibitor. These data show that activation of G6PD is associated with enhancement of oxidative inflammation in during ALI. Therefore, inhibition of G6PD might be a beneficial strategy during ALI to limit oxidative damage and ameliorate airway inflammation.

Acoustic puncture assist device: A novel technique to identify the epidural space.

BACKGROUND: Acoustic puncture assist device (APAD) is designed to detect and signal the loss of resistance during the epidural procedure. We aimed to evaluate this device in terms of successful identification of the epidural space and the incidence of accidental dural puncture. PATIENTS AND METHODS: Following Institutional Review Board approval and written informed consent obtained from all patients, 200 adult patients (107 males) American Society of Anesthesiologists I-III who underwent lower limb orthopedic surgery under lumbar epidural anesthesia using APAD were enrolled in the study. APAD system was connected to the epidural needle using normal saline prefilled extension tube. Numbers of successful epidural attempts and accidental dural tap were documented. RESULTS: The mean values of the depth of epidural space and the time to perform epidural puncture were 5.8 ± 1.0 cm and 3.3 ± 1.4 min, respectively. In 63% of patients, epidural puncture was successful from the first attempt and in 1% it was successful from the fourth attempt. Epidural anesthesia by APAD was successful in 198 cases (99 %). Dural tap occurred in 2 cases (1%). CONCLUSIONS: Using APAD, the success of identifying the epidural space was high and reliable.

Natural history and management of congenital hypothyroidism with in situ thyroid gland.

BACKGROUND/OBJECTIVE: Normally sited glands account for increasing congenital hypothyroidism (CH). Mechanisms often remain unknown. To report the incidence of CH with in situ thyroid gland (ISTG) and describe the natural history of the disease without known etiology. METHOD: Clinical, biochemical and imaging data at diagnosis were retrospectively analyzed in 285 children positively screened for CH in Ile-de-France between 2005 and 2008. If treatment was discontinued, management of hormonal substitution and follow-up of biochemical thyroid function was performed. RESULTS: 93 full-term CH neonates displayed ISTG (40.6%), including 50 with unexplained mechanism. Follow-up data were available in 32 of them. Therapy was withdrawn from 20 children at a median age of 23.5 months (6-66), among whom 18 remained still untreated over a median duration of 15.3 months (4.4-29.6). In 11 children, levothyroxine (L-T4) dosage was increased over time to maintain biochemical euthyroidism. No statistical differences in initial TSH or FT4 levels, iodine status or birth weight were found between children with transient and permanent hypothyroidism. CONCLUSION: Withdrawal of L-T4 substitution was feasible in 56.2% of full-term children with CH with ISTG but unexplained mechanism, emphasizing the need for systematic therapy withdrawal. However, further studies are warranted to standardize withdrawal protocol.

Salubrious effects of dexrazoxane against teniposide-induced DNA damage and programmed cell death in murine marrow cells.

The intention of the present study was to answer the question whether the catalytic topoisomerase-II inhibitor, dexrazoxane, can be used as a modulator of teniposide-induced DNA damage and programmed cell death (apoptosis) in the bone marrow cells in vivo. The alkaline single cell gel electrophoresis, scoring of chromosomal aberrations, micronuclei and mitotic activity were undertaken in the current study as markers of DNA damage. Apoptosis was analysed by the occurrence of a hypodiploid DNA peak and caspase-3 activity. Oxidative stress marker such as intracellular reactive oxygen species production, lipid peroxidation, reduced and oxidised glutathione were assessed in bone marrow as a possible mechanism underlying this amelioration. Dexrazoxane was neither genotoxic nor apoptogenic in mice at the tested dose. Moreover, for the first time, it has been shown that dexrazoxane affords significant protection against teniposide-induced DNA damage and apoptosis in the bone marrow cells in vivo and effectively suppresses the apoptotic signalling triggered by teniposide. Teniposide induced marked biochemical alterations characteristic of oxidative stress including accumulation of intracellular reactive oxygen species, enhanced lipid peroxidation, accumulation of oxidised glutathione and reduction in the reduced glutathione level. Prior administration of dexrazoxane ahead of teniposide challenge ameliorated these biochemical alterations. It is thus concluded that pretreatment with dexrazoxane attenuates teniposide-induced oxidative stress and subsequent DNA damage and apoptosis in bone marrow cells. Based on our data presented, strategies can be developed to decrease the teniposide-induced DNA damage in normal cells using dexrazoxane. Therefore, dexrazoxane can be a good candidate to decrease the deleterious effects of teniposide in the bone marrow cells of cancer patients treated with teniposide.

A new technique of flexor profundus repair in the distal part of zone I: inclusion of the palmar plate.

Flexor profundus lacerations in the distal part of zone I are usually treated by tendon reinsertion into bone. We present a modified technique in which three 'figure of eight' sutures include the palmar plate in the distal purchase. Inclusion of the palmar plate significantly strengthens the tensile strength of the repair and this was confirmed biomechanically in an experimental study. In a prospective clinical study, 15 patients with clean-cut complete lacerations of the profundus tendon in the distal part of zone I underwent the modified repair technique of three separate 'figure of eight' sutures with the palmar plate included in the suture distally and 7 mm suture purchase proximally, with postoperative immediate active motion that ensured full active extension of the interphalangeal joints. There were no ruptures or infections. At final follow-up 12-25 weeks after surgery, the mean range of motion at the distal, proximal, and combined interphalangeal joints was 66 degrees, 100 degrees and 166 degrees respectively. All patients achieved an excellent or good outcome.

Obstetric brachial plexus palsy in newborn babies of diabetic and non-diabetic mothers.

Compared to non-diabetic mothers, diabetic mothers are known to deliver larger babies who are at higher risk for shoulder dystocia and obstetric brachial plexus palsy. The intrapartum forces applied during delivery of larger babies are expected to be higher. Hence, the chances of these babies for good spontaneous recovery are expected to be lower; and this is a generally believed hypothesis. The objective of this retrospective study was to compare obstetric brachial plexus palsy in newborn babies of diabetic and non-diabetic mothers. There were a total of 655 cases of obstetric palsy: 253 cases with diabetic mothers and 402 with non-diabetic mothers. The former were more likely to develop total palsy while the latter were more likely to develop extended Erb's palsy. Newborn babies of diabetic mothers had significantly larger birth weights than those of non-diabetic mothers regardless of the type of palsy. The rate of good spontaneous recovery of the motor power of the limb in the two groups was not significantly different except in total palsy cases for shoulder external rotation and elbow flexion where the recovery was significantly better in the diabetic group. It was concluded that the generally believed hypothesis is not correct if one compares the outcome in the diabetic and non-diabetic groups for each type of palsy.

Obstetric brachial plexus palsy: a comparison of affected infants delivered vaginally by breech or cephalic presentation.

In this retrospective study we compared obstetric brachial plexus palsy (OBPP) in two non-operated groups of newborn babies delivered vaginally by breech or cephalic presentation. There were 35 cases of OBPP in the breech group and 663 cases in the cephalic group. The former group was more likely to develop upper Erb's palsy while the latter group was more likely to develop total palsy. The breech group also had a significantly lower mean birth weight, a significantly higher percentage of bilateral OBPP palsies and concurrent phrenic nerve palsy. Spontaneous recovery of shoulder abduction and elbow flexion in newborn babies with upper Erb's palsy was significantly worse in the breech compared with the cephalic group. It was concluded that OBPP following vaginal breech delivery has several unique demographic features and breech babies with upper Erb's palsy have a worse prognosis for spontaneous recovery than those in the cephalic group.

Narakas classification of obstetric brachial plexus palsy revisited.

Narakas classified babies with obstetric palsy into four groups: upper Erb's, extended Erb's, total palsy, and total palsy with a Horner. Over the last 15 years, it was noted at our obstetric palsy clinic that good spontaneous recovery in newborns with extended Erb's palsy (C5, C6, C7 injury) was more likely if they recovered active wrist extension against gravity before 2 months of age. A hypothesis was made that newborns with extended Erb's palsy (Narakas Group II) may be subclassified into two groups according to this 'early recovery of wrist extension.' In a retrospective study of 581 cases with strict inclusion criteria, the hypothesis was found to be true: patients with extended Erb's and 'early recovery of wrist extension' have significantly higher percentages of good spontaneous recovery of limb function than those with extended Erb's and 'no early recovery of wrist extension' (P<0.0001 by chi-squared test).

Boric acid enhances in vivo Ehrlich ascites carcinoma cell proliferation in Swiss albino mice.

The influence of boric acid, a boron carrier, on Ehrlich ascites carcinoma (EAC) cell-bearing mice was investigated in view of its importance in the boron neutron capture therapy and the influence of boron on proliferation and progression of cancer cells mediated by proteoglycans and collagen. The present study included the evaluation of boric acid for the effects on total count and viability of EAC cells in addition to their non-protein sulfhydryls (NP-SH) and malondialdehyde (MDA) contents as parameters for conjugative detoxication potency and possible oxidative damage. The EAC cell-bearing animals were also observed for the effect on survival, body weight changes, and histopathological evaluation of the tumors grown at the site of inoculation. The treatment with boric acid significantly increased the total number of peritoneal EAC cells and their viability. A significant increase in the body weight was observed that dose-dependently reached plateau levels by 20 days of treatment. Conversely, a reduction in the duration of survival of these animals was evident with the same protocol. Boric acid treatment resulted in a decrease in NP-SH contents with a concomitant increase in MDA levels in EAC cells as revealed by the results of the biochemical analysis. These data are supported by our results on histopathological investigations, which apparently showed fast growth, in addition to several mitotic figures and mixed inflammatory reaction, after treatment with boric acid. It seems likely that a particular combination of properties of boric acid, rather than a single characteristic alone, will provide useful information on the use of this boron carrier in neutron capture therapy.

Tract microflora in Saudi patients with cholelithiasis.

OBJECTIVES: To identify the microflora in the gallbladder of patients undergoing laparoscopic cholecystectomy for gallstones, and the antibiotic susceptibility pattern of the isolates, as well as the usefulness of Gram staining of bile at the time of operation. METHODS: Bile samples were obtained from 112 patients undergoing elective laparoscopic cholecystectomy for gallstones and inoculated directly into aerobic and anaerobic blood culture bottles in the operating theatre. Samples were also collected in sterile universal containers for Gram staining of a centrifuged deposit. Isolates were identified and their in-vitro susceptibilities determined by Kirby Bauer technique. RESULTS: Of 112 bile samples examined, 28 (25%) were culture positive, four of which contained more than one organism. The most common organisms isolated were Escherichia coli 9 (28.1%), Enterococcus faecalis 5 (15.6%) and Pseudomonas aeruginosa 3 (9.4%). In one sample we found Aeromonas hydrophilia and Enterobacter cloacae. No anaerobes were detected but Candida albicans was isolated in one case. In 19 bile samples (67.8%) organisms were identified on Gram stain. Positive bile cultures were found statistically significant (P < 0.05) in patients over the age of 50 (13/32), in patients who developed post-operative fever (6/12) and patients who developed leucocytosis (5/6). CONCLUSION: Age over 50 years was the only significant pre-operative factor associated with positive bile cultures (P < 0.05). In view of the microflora of the gallbladder and the susceptibility pattern of our isolates we would suggest that antibiotic prophylaxis recommended for laparoscopic cholecystectomy for gallstones needs to be reviewed and the role of bacteribilia in the surgical management of cholelithiasis requires further study.

Accidental injuries during muslim pilgrimage.

OBJECTIVE: The diseases that occur during Hajj are a unique medical problem. The aim of this study is to highlight the incidence, the type and the early surgical management of trauma during the Hajj period. METHODS: A prospective study was carried out during a 15 day-period conducted in two parts in the emergency room, and a follow-up of the admitted patients in the surgical department. RESULTS: The number of trauma cases who attended the emergency department was 713 patients, 248 patients were admitted in different surgical departments, together with the intensive-care unit. Sixty-five percent of the patients were discharged from emergency room as they had minor trauma. Sixty percent were involved in road traffic accidents, 15% had injuries in Holy Haram. Limb fracture accounts for 53% of total trauma admissions. Two patients died in the first 48 hours. CONCLUSION: Trauma during Hajj is a real surgical problem which deserves more attention. Orthopedic and Neurosurgical cases are the most common surgical cases during the Hajj period.

Accidental injuries during muslim pilgrimage.

OBJECTIVE: The diseases that occur during Hajj are a unique medical problem. The aim of this study is to highlight the incidence, the type and the early surgical management of trauma during the Hajj period. METHODS: A prospective study was carried out during a 15 day-period conducted in two parts in the emergency room, and a follow-up of the admitted patients in the surgical department. RESULTS: The number of trauma cases who attended the emergency department was 713 patients, 248 patients were admitted in different surgical departments, together with the intensive-care unit. Sixty-five percent of the patients were discharged from emergency room as they had minor trauma. Sixty percent were involved in road traffic accidents, 15% had injuries in Holy Haram. Limb fracture accounts for 53% of total trauma admissions. Two patients died in the first 48 hours. CONCLUSION: Trauma during Hajj is a real surgical problem which deserves more attention. Orthopedic and Neurosurgical cases are the most common surgical cases during the Hajj period.

Effect of ninhydrin on the biochemical and histopathological changes induced by ethanol in gastric mucosa of rats.

Studies on the effect of ninhydrin in the normal gastric mucosa and against the ethanol induced gastric injury were undertaken in rats in view of the presence of a carbonyl function as well as hydroxyl groups in its chemical structure. In spite of its potentials to generate hydroxyl radicals, it is deemed to possess antioxidant property by virtue of its electrophilic nature. Recent studies have shown gastro-protection to mediate through a reaction between the electrophilic compounds and sulfhydryl groups of the mucosa. Hence it was found worthwhile to evaluate the interaction between the oxidant and antioxidant functions in the structure of the same compound. The effects of ninhydrin pretreatment on gastric mucosal injuries caused by 80% ethanol, 25% NaCl and 0.2M NaOH were investigated in rats. The gastric tissue in ethanol-treated rats was analyzed for different histopathological lesions. In addition, the effects on ethanol-induced changes in the gastric levels of proteins, nucleic acids, non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also evaluated. Ninhydrin, as such, failed to induce any significant changes in normal gastric mucosa, while its pretreatment at oral doses of 5, 10 and 20 mg/kg was found to provide a dose-dependent protection against the ulcers induced by ethanol, NaOH and NaCl. The results of histopathological evaluation revealed a protective effect of ninhydrin on congestion, hemorrhage, edema, erosions and necrosis caused by ethanol. Furthermore, the pretreatment afforded a dose-dependent inhibition of the ethanol-induced depletion of proteins, nucleic acids, NP-SH and increase of MDA in the gastric tissue. The results obtained clearly demonstrate the anti-ulcerogenic activity of ninhydrin. The exact mechanism of action is not known. However, the carbonyl function in ninhydrin appears to achieve antioxidant balance and protect the gastric mucosa from the ethanol-induced gastric injury. Further studies are warranted to investigate the toxicity and detailed mechanism of action of this potent compound before any clinical trials, especially at the effective lower doses.

Inhibition of gastric mucosal damage by methylglyoxal pretreatment in rats.

The effect of methylglyoxal pretreatment on gastric mucosal injuries caused by 80% ethanol, 25% NaCl and 0.2 M NaOH, was investigated in rats. The effects caused by pylorous ligation accumulated gastric acid secretions and ethanol-induced changes in gastric mucus secretions, levels of proteins, nucleic acid, malondialdehyde (MDA) and non-protein sulfhydryl groups were also investigated. Methylglyoxal pretreatment at oral doses of 50, 100 and 200 mg/kg body weight was found to provide a dose-dependent protection against the ulcerogenic effects of different necrotizing agents used. With the same dose regimen methylglyoxal offered significant protection against ethanol-induced damage on the parameters evaluated for histopathology. Furthermore, the pretreatment afforded a dose-dependent inhibition of pylorous ligated accumulation of gastric acid secretions and ethanol-induced depletion of stomach wall mucus, proteins, nucleic acids, NP-SH contents and an increase in the MDA levels in gastric tissue. The protective effect of methylglyoxal against ethanol-induced damage to the gastric wall mucosa may be mediated through its effect on mucous production, proteins, nucleic acids, NP-SH groups and its free-radical scavenging property under the influence of polyamines stimulated by ornithine decarboxylase activity (ODC).

Studies on the cytotoxic, biochemical and anti-carcinogenic potentials of ninhydrin on Ehrlich ascites carcinoma cell-bearing Swiss albino mice.

Ninhydrin (2,2-dihydroxy-1,3-indane dione) was evaluated for its antitumor and cytotoxic properties in Ehrlich ascites carcinoma cell (EAC Cell)-bearing mice. The rationale behind this study has been mainly the literature reports of its characteristic interference with DNA synthesis and calcium homeostasis. Antitumor activity was evaluated from the total count and viability of EAC cells in addition to their nucleic acid, protein, non-protein sulfhydryls (NP-SH) and malondialdehyde (MDA) contents. The EAC cell-bearing animals were also observed for the effect on their survival and body weight variations. In addition, the tumors grown at the site of injection were evaluated for histopathological changes. Ninhydrin treatments (5, 10 and 20 mg/kg/day) abate the increase in body weight and advanced the duration of survival in EAC cell-bearing mice. The results on histopathological investigations show retardation in tumor growth, decreased frequency of mitotic figures and hair follicles and an increased necrosis in the tumor by ninhydrin treatment. Our results on cytotoxicity, which demonstrated compression in the number of EAC cells and their viability substantiate these data. The results of biochemical studies on EAC cells exhibit a reduction in the levels of DNA, RNA, proteins and NP-SH with a subsequent increase in the concentrations of MDA after ninhydrin treatment. Inhibition in tumor growth was dose dependently significant with the same dose regimen. The observed cytotoxic and antitumor activity of ninhydrin was comparable to cyclophosphamide. The possible mode of action of ninhydrin-induced cytotoxic and antitumor activity appear to be due to its interference with mitochondrial function resulting in inhibition of DNA synthesis, an effect that is being investigated further.

Predictors for morbidity and mortality following non-traumatic splenectomy at the University Hospital, Jeddah, Saudi Arabia.

OBJECTIVE: To determine the pre-operative predictors of morbidity and mortality of patients undergoing elective splenectomy for non-trauma indications. METHODS: Analysis of 123 patients who underwent splenectomy at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 1986-1996. Data collected included patients' demographic data, indication for splenectomy, laboratory data, details of operative procedure and postoperative events for morbidity and mortality. Statistical analysis was carried out using the Chi-square test. RESULTS: Of the patients, 69% were males and 31% females with ages ranging from 13-72 years (mean 39 years). Portal hypertension constituted 55% of the indications and benign hematological conditions 26%. The morbidity rate was 27.6% and the commonest complication was chest and wound infection in 6.6% and 5.7%, respectively. Age of >50 years, pre- and postoperative haematocrit of <33%, thoraco-abdominal approach and operative time of >120 min had P values of < 0.05, <0.002, <0.03 and <0.03, respectively for postsplenectomy mortality. CONCLUSIONS: According to this study, age of >50 years is a significant predictor for morbidity following splenectomy, whereas age >50 years, pre- and postoperative haematocrit of <33%, thoraco-abdominal approach and operative duration >120 min were significant predictors of postsplenectomy mortality.

Pattern of surgical and medical diseases among pilgrims attending Al-noor hospital makkah.

OBJECTIVE: Hajj usually presents a unique medical crisis especially for the Emergency Department. This study will identify the surgical and medical cases that presented at the Emergency Department during Hajj and percentage admitted. DESIGN: A prospective study of the pattern of surgical and medical cases that presented at the Emergency Department of the largest tertiary care hospital in Makkah city and holy lands during Hajj. METHODS: The study was conducted prospectively during the 1413 (1993) Hajj pilgrimage from 20.11.1413 to 20.12.1413. All Saudi and non-Saudi pilgrims presenting at the Emergency Department of Al-Noor Specialist Hospital were included. RESULTS: From the 7,676 patients who came to the Emergency Department, 1426 were admitted. The commonest cause for surgical admission was trauma, while the commonest cause for medical admission was pneumonia. CONCLUSION: More than 50% of cases could have been dealt with in the Outpatient Department or Primary Health Care Centers.

Minimal invasive surgery: a district hospital experience.

This was a prospective analysis of the first 162 patients who underwent biliary and nonbiliary minimally invasive (video laparoscopic) procedures in the Royal Commission Medical Centre (RCMC) over two periods separated by a one year interval (September 1993-September 1994)-(October 1995-February 1996). One hundred and fifty patients had video laparoscopic cholecystectomy (VLC). Thirty four males and 116 females with a mean age of 39.7 years (range 16-80). Forty two patients (28%) were admitted as emergency (37 acute cholecystitis, 5 acute pancreatitis). The indication for VLC was symptomatic gall stones. The VLC was accomplished successfully in 144 patients (96%). Six patients (2 electives and 4 emergency) required a conversion for various reasons, unfavourable anatomy being the commonest. Ten patients with preoperative evidence of a dilated common bile duct, with or without stones had an ERCP done in another hospital 200 km away. The median operative time was 100 minutes (range 30-270 minutes) There were three major complications (one CBD injury, one bleeding from gall bladder bed and one post operative acute pancreatitis) and 6 minor complications (urethral bleeding, atelectasis post-operative pyrexia, umbilical port cellulitis, prolonged ileus and acute anxiety state). The median hospital stay was 72 hours for successful VLC. Twenty five per cent of the patients did not require any narcotic analgesic. Twelve patients (7.4%) had one or another non-biliary video laparoscopic procedure. Our results suggest that VLC can be offered and performed safely in the majority of patients presenting with acute and/or chronic cholecystitis and that the results we achieved in a district hospital are comparable to other series. We conclude that VLC will continue to be demanded by patients and non-biliary video laparoscopic procedures which were slow to develop in our hospital will continue to need special training, interest and expertise before it can be adopted as a routine.