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According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5 years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most., (© 2018 The Association for the Publication of the Journal of Internal Medicine.)

Purpose: To evaluate the effectiveness and safety of hydrocortisone (HC) in cancer patients with septic shock., Methods: This was a retrospective study of adult cancer patients with septic shock who received low-dose HC therapy (200 mg/day). The effectiveness of HC was assessed by determining the proportion of patients with reversal of septic shock, time to reversal, and mortality. The safety was assessed by determining the incidences of hyperglycemia, hypernatremia, and secondary infections, using a case-control approach., Results: During the study period, 96 patients were enrolled. Reversal of septic shock was reported in 46 (47.9%) patients, median time to reversal was 1.9 days (range 0.2-7.6), ICU mortality was reported in 62 (65.26%) patients, and 28-day mortality in 64 (66.7%) patients. The incidence of secondary infections was higher in patients who received HC therapy, compared to patients who did not receive HC during septic shock: 44.8% vs 27.4%, P = 0.028., Conclusions: HC therapy was associated with resolution of septic shock in about half of the patients and a high incidence of secondary infections. Prospective studies are needed to fully assess the efficacy and safety of HC in cancer patients with septic shock., (© The Author(s) 2014.)

Objective: To evaluate the available evidence regarding the efficacy and safety of rifampicin, as adjunct to colistin, in the treatment of multidrug resistant Acinetobacter baumannii (MDR-AB)., Data Sources: We searched MEDLINE (1966 to January 2014) using the following search terms: A baumannii, drug resistance, treatment, colistin, and rifampicin and combinations. In addition, the bibliographies of relevant articles were searched for additional citations., Study Selection and Data Extraction: The search was limited to English-language references and adults. Studies in which colistin was not administered intravenously were excluded. In addition, we excluded meeting abstracts and single case reports., Data Synthesis: The search strategy identified 5 observational studies and 2 randomized controlled trials that evaluated the combination of intravenous colistin and rifampicin for the treatment of MDR-AB. All observational studies included a small sample size, and the microbiological clearance associated with the combination therapy ranged from 60% to 100%. The randomized controlled trials reported reduced time to microbiological clearance and higher microbiological eradication rate in the colistin/rifampicin group compared with colistin alone. However, there was no difference between both groups in the overall mortality, infection-related mortality, and the length of stay. Furthermore, rifampicin was associated with a higher incidence of hepatotoxicity., Conclusions: Studies evaluating the combination of rifampicin and colistin in the treatment of MDR-AB are limited. The currently available evidence does not support the addition of rifampicin to colistin because of the lack of improved clinical outcomes with the combination therapy and the risk of rifampicin-induced hepatotoxicity.

Background: Cancer patients are at high risk for developing sepsis. To our knowledge, there are no studies that evaluated the type of medications utilized and the associated cost in cancer patients with severe sepsis and septic shock., Objective: To describe the drug utilization pattern and drug cost in the treatment of cancer patients with severe sepsis and septic shock., Setting: 12-bed medical/surgical intensive care unit (ICU) of a comprehensive teaching cancer center., Methods: A retrospective cohort study of cancer patients with severe sepsis or septic shock who were treated in the ICU between January and December, 2010. The ICU sepsis database was used to identify patients. The patient demographics and characteristics were recorded. In addition, the number and type of prescribed medications, total cost for each medication, type of infection, and culture results were determined., Main Outcome Measure: The main outcomes were the type of medication classes utilized and the cost of the medications., Results: During the study period, 116 cases were identified. Upon presentation, the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 21.8 (SD ± 7.8), 30 (25.9 %) patients had neutropenia, and 94 (81 %) had positive cultures. The total cost of the medications prescribed for this cohort of patients was 291,030 Euro. The mean number of medications prescribed per patient and the mean total cost per patient were 11.7 (SD ± 4.7) and 2,509 Euro (SD ± 2,844), respectively. The most commonly prescribed medication classes were acid suppressive therapy, glycopeptides, penicillins/cephalosporins and vasopressors prescribed in 113 (97 %), 104 (89.7 %), 103 (88.9 %), and 102 (88 %) patients, respectively. The highest medication costs were associated with antifungals (mean 1,288 Euro/patient) and colony stimulating factors (mean 829 Euro/patient), prescribed in 55 (47.4 %) and 37 (31.9 %) patients, respectively. Medication costs were higher in non-survivors, compared to survivors (3,664 Euro vs. 1,430 Euro, p = 0.0001), and in patients with positive cultures, compared to patients with negative cultures (3,198 Euro vs. 1,865 Euro, p = 0.0004)., Conclusion: In cancer patients with severe sepsis and septic shock, multiple medications are prescribed which are associated with high cost.

Objective: To evaluate the efficacy and risks of complications of pulse dosing of topical 5-fluorouracil (5-FU) in the treatment of corneal intraepithelial neoplasia (CIN), and conjunctival squamous cell carcinoma (SCC)., Design: Prospective, noncomparative case series., Participants: Fifteen patients with histological evidence CIN or SCC of the conjunctiva and cornea were identified by tumor biopsy., Methods: All patients clinically evident of CIN, or SCC were evaluated, with maximum 30 months of follow-up were treated with pulsed dosing of 1% 5-FU. Treatment cycles were defined as four times per day for 4 days using the medication followed by 30 days without medication. The number of initial treatment was six cycles., Results: The mean age of the 15 patients was 50.8 years (range 25-78 years). Excision biopsy proved seven cases as CIN, and eight cases as locally invasive SCC. All patients remained disease free with a mean follow-up of 14.53 months (range 6-30 months). Additional chemotherapy was given after the initial treatment cycles, only for one case. 5-FU caused mild temporary local irritation, but no long-term intraocular or extra ocular complications., Conclusions: Adjuvant 1% topical 5-FU appears to be effective in the prevention of recurrence of conjunctival or corneal CIN and SCC after excision biopsy. Our results indicate that at least six cycles of topical 1% 5-FU is required to prevent local recurrence in the long term. It is well-tolerated and an effective method of treatment. No complications that would preclude use of our dose regimen were noted.

Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecular biomarkers that are produced by melanoma or non-melanoma cells. A number of these biomarkers demonstrate promising results as possible methods for early detection, predicting recurrence and monitoring therapy. Other biomarkers appear to be promising for identifying patients at risk for metastasis. We reviewed the most pertinent information in the field thus far and how this knowledge can impact, or not, the management of melanoma patients prognostically and therapeutically.

Background and Objective: Circulating tumor cells have been shown to correlate positively with metastatic disease state in patients with advanced cancer. We have demonstrated the ability to detect melanoma cells in a flow system by generating and detecting photoacoustic waves in melanoma cells. This method is similar to flow cytometry, although using photoacoustics rather than fluorescence. Previously, we used piezoelectric films as our acoustic sensors. However, such films have indicated false-positive signals due to unwanted direct interactions between photons from the high laser fluence in the flow system and the film itself. We have adapted an optical detection scheme that obviates the need for piezoelectric films., Study Design/materials and Methods: Our photoacoustic system comprised a tunable laser system with an output of 410-710 nm with a pulse duration of 5 nanoseconds. The light was delivered by optical fiber to a glass microcuvette that contained saline buffer suspensions of melanoma and white blood cells. We used a continuous HeNe laser to provide a probe beam that reflected off of a glass and water interface in close proximity to the microcuvette. The beam was detected by a high-speed photodiode. When a photoacoustic wave was generated in the microcuvette, the wave propagated and changed the reflectance of the beam due to index of refraction change in the water. This perturbation was used to detect the presence of melanoma cells., Results: We determined a detection threshold of about one individual melanoma cell with no pyroelectric noise indicated in the signals., Conclusions: The optical reflectance method provides sensitivity to detect small numbers of melanoma cells without created false-positive signals from pyroelectric interference, showing promise as a means to perform tests for circulating melanoma cells in blood samples.

Purpose: To study the point prevalence of pseudoexfoliation syndrome (PXS) among Yemeni patients in different governorates with age-related cataract scheduled for surgery., Settings: Eye camps organized by the Nibras Health Society to perform cataract surgeries during the years 2002-2006. All patients aged 40 years and above were included in the study., Materials and Methods: A total of 2535 eyes of 2535 patients from 13 governorates, scheduled for cataract surgery in eye camps, were included. All eyes underwent complete eye examination before the surgery and were evaluated for the signs of pseudoexfoliation material in the pupil, iris and lens capsule on dilated slit lamp examination., Results: The study found 495 of the 2535 eyes (19.53%) with PXS with males more commonly affected than females (55.2 and 44.8%, respectively). The mean age of patients with PXS was 66.2 years while it was 64.6 years in non-PXS patients. The prevalence of pseudoexfoliation syndrome increased with age (10.1% in the age group of 41-50 years that increased to 28.8% in the age group of more than 81 years old). The rate of PXS detection in camps in 13 governorates ranged from 13.33 to 24.22% with an overall rate of 19.53%. The lowest rate was noticed in Sana'a and the highest in Al-Dhale governorate., Conclusion: This pilot study confirms that PXS was common in patients undergoing cataract surgery in Yemen with an increased detection rate with age. This study also highlights the prevalence of an ocular disease that is associated with systemic and ocular complications; however, further studies based on population studies are needed.

Melanoma is the deadliest form of skin cancer and has the fastest growth rate of all cancer types. Proper staging of melanoma is required for clinical management. One method of staging melanoma is performed by taking a sentinel node biopsy, in which the first node in the lymphatic drainage path of the primary lesion is removed and tested for the presence of melanoma cells. Current standard of care typically involves taking fewer than ten histologic sections of the node out of the hundreds of possible sections available in the tissue. We have developed a photoacoustic method that probes the entire intact node. We acquired a lymph node from a healthy canine subject. We cultured a malignant human melanoma cell line HS 936. Approximately 1 x 10(6) cells were separated and injected into the lymph node. We also had a healthy lymph node in which no melanoma cells were implanted. We used a tunable laser system set at 532 nm to irradiate the lymph nodes. Three piezoelectric acoustic detectors were positioned near the lymph node to detect photoacoustic pulses generated within the lymph nodes. We also acquired lymph nodes from pigs and repeated the experiments with increased amplification and improved sensors. We detected photoacoustic responses from a lymph node with as few as 500 melanoma cells injected into the tissue, while normal lymph nodes showed no response. Photoacoustic generation can be used to detect melanoma micrometastasis in sentinel lymph nodes. This detection can be used to guide further histologic study of the node, increasing the accuracy of the sentinel lymph node biopsy.

Purpose: To compare the effect of oral acetazolamide and topical 2% dorzolamide in prevention of ocular hypertension after scleral tunnel cataract surgery., Setting: Ophthalmic department, Sana'a University, Yemen Sana'a from March 2007 to October 2007., Methods: This prospective double-blind, randomized study included 150 eyes undergoing scleral tunnel cataract surgery with hard posterior chamber intraocular implantation. Methylcellulose was used as the viscoelastic in all surgery cases. Patients were assigned to one of three groups: group 1: topical gentamicin eye drops (control; n = 52); group 2: systemic acetazolamide 250 mg (n = 45); and group 3: topical 2% dorzolamide (n = 53). Acetazolamide patients received one 250 mg tablet, one hour before surgery, then half a tablet every eight hours. A topical dorzolamide 2% or gentamicin was applied in one drop one hour before surgery then every eight hours, for three days postoperatively. Intraocular pressures (IOP) were measured by Goldman applanation tonometry one hour preoperatively and 16, 24, and 48 hours postoperatively., Results: At 16 hours, IOP between the three groups increased significantly with a statistically significant p-value of 0.008, but the mean IOP of acetazolamide patients was less than other groups. IOP nearly returned to the normal level 24 and 48 hours postoperatively, but this was not statistically significant (p = 0.452 and 0.138, respectively)., Conclusion: Acetazolamide offers better IOP control than topical dorzolamide 2% in preventing ocular hypertension after scleral tunnel cataract surgery.

To determine the incidence and management of urological complications after live-donor renal transplantations at our center, we studied the medical records of 122 patients who underwent live kidney transplantation with a stented Lich-Gregoire anastomosis for ureteric reimplantation. The overall incidence of urological complications was 7.3 %. The early complications included four cases of ureteric stenosis, two cases of urinary leaks (one vesical fistula and one ureterovesical fistula) and one case of lymphocele causing ureteric obstruction. On the other hand, the late complications (> 6 months after surgery) included two cases of vesicoureteral reflux. No graft was lost and there was no urinary complication-related mortality. There was no association with recipient age, related or non-related donor or cold ischemic time. The urinary complications were mostly caused by ureteral ischemia and extrinsic compression by lymphocele; the stent caused vesicular fistula in one patient and clot anuria caused ureteral obstruction in another. In conclusion, the Lich-Gregoire technique has low complication rate and technical ease to perform compared with Barry's extravesical technique.

Between October 1985 and the end of 1998, 259 renal transplantations were performed at Al-Mouassat University Hospital in Damascus, from living related donors (LRD). The age of the patients ranged from 14 to 57 years with a mean age of 31.1 years. There were 208 (80.3%) males and 51 (19.7%) females. The follow-up ranged from 1-159 months. The immunosupression therapy was azathioprine and prednisone in 71 patients, and cyclosporine, azathioprine and prednisone in 188 patients. The one, three and five year graft survival was 98.2%, 92.1% and 85.8% respectively. The one, three and five year patient survival was 99%, 97.2% and 90.1% respectively. The ten years overall patient survival was 70.2%. The incidence of complications encountered was acceptable and similar to that reported in the literature. Our study shows that the efficacy of the overall results in our center is comparable to that published in the western world.