Immunity waning after COVID vaccine booster vs. infection-better than expected.

BACKGROUND: Rapid decline in antibody-titres after BNT162b2 mRNA COVID-19 vaccine was reported; thus, a booster dose, and recently a second booster were approved. The study aims to discuss immunogenicity throughout the pandemic, especially after booster dose. METHODS: A prospective study conducted in EMMS-Nazareth hospital, Israel. Anti-SARS-CoV-2 IgG antibody titres were monitored every 5 weeks starting from the vaccine's second dose. To detect symptomatic and asymptomatic infections, nasopharyngeal swabs for COVID-19 PCR were obtained bi-weekly, and on suggestive symptoms. Third dose of the vaccine was suggested for all participants 5 months after the second one. A comparison was made between those who received three doses (booster-group), and those who were infected after having two doses (infection-group) or three doses (booster-infection) group. RESULTS: One-hundred participants were included; 66 finished 14 months of follow-up, out of whom 40 received a third dose, 10 received only two doses-all were infected (mean time for infection 5 ± 12.15 weeks before the designated booster), and 12 received three doses and were infected. The mean titres of these three groups 7 months after the designated booster dose (regardless of receiving it) were 1756 ± 2279; 3483 ± 3016 and 6925 ± 3720 BAU/mL, respectively. The booster group had high titres 7 months after the booster dose, comparable to two months after the second dose (p = .69); The booster-infected group had even higher titres. CONCLUSION: Immunogenicity decline rate after the booster dose is slower than the second dose. Timing of second booster in general population is still to be determined; neutralizing-antibody titres might be helpful.

COVID-19 vaccine - Long term immune decline and breakthrough infections.

BACKGROUND: Since the introduction of BNT162b2 mRNA COVID-19 vaccine by Pfizer in late 2020, efficacy and immunogenicity waning of COVID-19 vaccines was reported, and decision making regarding a booster remains a top priority worldwide, a decision that should be made based on breakthrough infection rate and antibody titer decline overtime. METHODS: We conducted a 5-month longitudinal prospective study involving vaccinated healthcare personnel, who were tested monthly for antibody titer, and sampled biweekly and on clinical indication for SARS-COV-2 polymerase chain reaction (PCR), to determine antibody decline and breakthrough infection. RESULTS: 100 participants were recruited to the study. Antibody titer reached the climate after one month of the second dose of the vaccine, and declined rapidly thereafter: the median antibody levels were 895; 22,266; 9,682; 2,554 and 1,401 AU/ml in the day of the second dose, and in one month interval thereafter, respectively. In other words, four months after vaccination, the mean antibody level was 6% of the peak levels. During the study period, 4 breakthrough infections were diagnosed, 2 of which were asymptomatic, and the remaining two were mild cases; sharp elevation of antibody titer was seen after infection. CONCLUSION: Antibody titer drops rapidly one month after the second dose of the vaccine. All infections within the study period were mild or asymptomatic, after which titer elevations were seen.

The impact of medical cannabis consumption on the oral flora and saliva.

OBJECTIVE: To evaluate the effect of medical cannabis consumption on oral flora and saliva. DESIGN: A clinical prospective study, at the rheumatology clinic of the Nazareth Hospital in Nazareth, recruiting consecutively patients approved for medical cannabis, evaluating their saliva flow, pH and microbial load of Streptococcus mutans and Lactobacillus, prior to and under medical cannabis treatment. METHODS: Patients recently licensed for medical cannabis treatment, were recruited just prior to starting medical cannabis consumption (week 0), 1 and 4 weeks later, patients provided 5-minute time saliva samples, which were measured for their volume and pH, and cultured on a special microbial kit, evaluating the growth of Streptococcus mutans and Lactobacillus. RESULTS: Out of 16 patients enrolled, 14 were female and had fibromyalgia. The mean age of the patients was 52.8±12.9 years. The mean saliva flow at week 0, week 1 and week 4 were 5.38±3.36 ml/5-minutes, 6 (p = 0.769) and 5.45 (p = 0.391), respectively, and for saliva pH were 6.28, 5.94 (p = 0.51) and 5.5 (p = 0.07) respectively also. The mean Streptococcus mutans growth score at weeks 0, 1 and 4 was1.8±0.75, 1.6±0.83 (p = 0.234), and 2.4±0.84 (p = 0.058), respectively. The mean Lactobacilli growth score at weeks 0, 1 and 4 was 2.59±0.88, 3.1±0.69 (p = 0.033) and 3.3±0.67 (p = 0.025), respectively. CONCLUSIONS: The results of this study show that medical cannabis consumption has no significant effect on saliva volume or pH, but it may be associated with changes in salivary levels of oral microbes such as Streptococcus mutans and Lactobacilli.

Predictors of in-hospital mortality among patients with clostridium difficile infection: a multicenter study.

BACKGROUND: Clostridium difficile infection (CDI)-associated mortality is a major global health concern. Several clinical and laboratory parameters have been linked to poor prognosis in patients with CDI. In the current study, we aimed to assess the rate of in-hospital mortality among Israeli CDI patients and to look for clinical and laboratory parameters associated to death. METHODS: We performed a multicenter retrospective study enrolling all patients above 18-years old who were hospitalized for CDI or with diagnosis made during hospitalization in two regional, teaching hospitals in the north of Israel (Galilee Medical Center, Nahariya and the Nazareth Hospital, Nazareth, Israel), from January 1, 2015 until January 1, 2020. All files of eligible patients were reviewed for demographic (age, gender), medical history and laboratory tests. RESULTS: Overall, we included in the study 180 patients, among them 56 died in hospital due to CDI (group A) while 124 survived (group B). The average age in groups A and B was 77.02±13 vs. 71.5±19.1, respectively. On univariate analysis, several clinical and laboratory parameters were associated with in-hospital mortality, including: advanced age, renal failure, antibiotics treatment while on treatment for CDI, need for mechanical ventilation, level of hemoglobin, white blood cells (WBC) and neutrophils count, neutrophil/lymphocyte ratio, serum level of albumin, creatinine and C reactive protein. On multivariate logistic regression analysis, only 4 parameters showed statistically significant association with in-hospital mortality, including age (odds ratio [OR]: 6.97, 95%confidence interval [CI]: 4.94-8.72, P=0.003), renal failure (OR: 3.72, 95% CI: 1.22-11.24, P=0.02), WBC count (OR: 1.09, 95% CI: 1.02-1.16, P=0.008), and lower albumin level (OR: 47.62, 95% CI: 10.31-200, P<0.0001). CONCLUSIONS: In this retrospective, multicenter study, age, serum albumin level, leucocytes count, and renal failure were the main predictors of in-hospital mortality in patients with CDI. Thus, antibiotic use should be weighed carefully in elderly comorbid patients, at increased risk of mortality from CDI .Prospective multicenter randomized studies investigating the effect of albumin infusion on in-hospital death of CDI patients are needed, thus enabling us to direct monitoring and treatment accordingly.

Impact of pretreatment with carnitine and tadalafil on contrast-induced nephropathy in CKD patients.

Objective: The present study assesses whether phosphodiesterase type 5 (PDE-5) inhibitor or carnitine exert nephroprotective effects against clinical contrast-induced nephropathy (CIN).Materials and Methods: The present study consisted of three groups of CKD patients. The first group was control group, who were treated with N-acetyl-L-cysteine 1 day before and on the day of radiocontrast administration. The second one was carnitine group, where the patients were infused with carnitine over 10 min 2 h prior to the radiocontrast administration and 24 h post CT. The third one was PDE-5 inhibitor group, where patients were given tadalafil 2 h prior to the administration of the radiocontrast and in the subsequent day. Urine and blood samples were collected before and at the following time sequence: 2, 6, 12, 24, 48, and 120 h after the contrast administration, for creatinine and NGAL determination.Results: Pretreated with N-acetyl-L-cysteine prior to administration of contrast media (CM) to CKD patients caused a significant increase in urinary but not of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr). In contrast, pretreatment with carnitine prevented the increase in urinary NGAL and reduced SCr below basal levels. Similarly, tadalafil administration diminished the elevation of CM-induced urinary NGAL.Conclusions: These results indicate that carnitine and PDE-5 inhibitors may comprise potential therapeutic maneuvers for CIN.

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia: A Rare Case Report from Nephrology.

BACKGROUND Tumor lysis syndrome is common in hematological malignancy, but less frequent in chronic and solid tumors. Almost always it is observed after chemotherapy or radiotherapy initiation, but rarely occurs spontaneously. CASE REPORT A 89-year-old female with stable chronic lymphocytic leukemia was admitted to the hospital because of worsening dyspnea and dry cough. Her vital signs were normal, except for sinus tachycardia. On physical examination, she appeared distressed, dyspneic, sweaty but afebrile, anxious, but alert and well oriented. Lung examination revealed reduced air entry with bibasilar crackles. No peripheral edema was seen, pulses were normal, and no signs of deep vein thrombosis were observed. Laboratory analysis revealed leukocytosis; but normal hematological and biochemical parameters. Intravenous (IV) furosemide and antibiotics (IV ceftriaxone and orally azithromycin) were started along with steroid therapy (methylprednisolone 62.5 mg, IV). The treatment with steroids lasted for 1 day only, and in the following day, the patient was switched to prednisone (20 mg/day orally) for only 1 additional day. White blood cell count increased on day 1, 2 and 3 after admission, along development of hyperuricemia, hyperphosphatemia, hyperkalemia, acute renal failure and elevated troponin levels. Hemodiafiltration/hemodialysis was initiated, and the patient was discharged after serum concentrations of these electrolytes and kidney function were restored. One month after discharge, the patient denied any malaise and was at stable condition. CONCLUSIONS Herein, we present a case of a patient with stable chronic lymphocytic leukemia, who developed spontaneous tumor lysis syndrome after short low dose of steroid therapy. This case highlights the importance of including spontaneous tumor lysis syndrome in the differential diagnosis of any acute renal failure in the constellation of any malignancy.

Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches.

Preeclampsia is a serious complication of pregnancy where it affects 5-8% of all pregnancies. It increases the morbidity and mortality of both the fetus and pregnant woman, especially in developing countries. It deleteriously affects several vital organs, including the kidneys, liver, brain, and lung. Although, the pathogenesis of preeclampsia has not yet been fully understood, growing evidence suggests that aberrations in the angiogenic factors levels and coagulopathy are responsible for the clinical manifestations of the disease. The common nominator of tissue damage of all these target organs is endothelial injury, which impedes their normal function. At the renal level, glomerular endothelial injury leads to the development of maternal proteinuria. Actually, peripheral vasoconstriction secondary to maternal systemic inflammation and endothelial cell activation is sufficient for the development of preeclampsia-induced hypertension. Similarly, preeclampsia can cause hepatic and neurologic dysfunction due to vascular damage and/or hypertension. Obviously, preeclampsia adversely affects various organs, however it is not yet clear whether pre-eclampsia per se adversely affects various organs or whether it exposes underlying genetic predispositions to cardiovascular disease that manifest in later life. The current review summarizes recent development in the pathogenesis of preeclampsia with special focus on novel diagnostic biomarkers and their relevance to potential therapeutic options for this disease state. Specifically, the review highlights the renal manifestations of the disease with emphasis on the involvement of angiogenic factors in vascular injury and on how restoration of the angiogenic balance affects renal and cardiovascular outcome of Preeclamptic women.

The Impact of Intra-articular Depot Betamethasone Injection on Insulin Resistance Among Diabetic Patients With Osteoarthritis of the Knee: A Case-Control Study.

OBJECTIVE: The aim of this study was to evaluate the impact of intra-articular corticosteroid injection (IACI) of depot betamethasone at the knee joint on insulin resistance (IR). METHODS: Patients with type 2 diabetes, non-insulin treated, with painful osteoarthritis of the knee were requested to participate in our study. After consent, demographic, clinical, and laboratory parameters were documented in addition to fasting blood glucose (FBG) and fasting blood insulin levels just prior to IACI of 1 mL of depot betamethasone. Fasting blood glucose and fasting blood insulin levels were repeated the next day following the IACI and 8 days later. Age- and sex-matched group of patients with type 2 diabetes from the same clinic were recruited as a control group (case-control study). Insulin resistance was calculated using Homeostasis Model Assessment-Insulin Resistance. Mann-Whitney U test, χ test, and Wilcoxon signed rank tests were used for statistical analysis. RESULTS: Eleven patients were recruited in the patients' group and 10 patients in the control group. Median FBG in the patients' group at baseline was 148 ± 51 mg/dL, and median IR was 5.12 ± 2.46. One day following the IACI, median FBG level was 247 ± 104 mg/dL (P = 0.004, compared with baseline), with median IR of 20.8 ± 7.01 (P = 0.0039). The median ratios of blood glucose and IR 1 day following the IACI compared with baseline were 1.7 and 4.1, respectively. Eight days following the IACI, mean FBG and IR levels were not significantly different from baseline. CONCLUSIONS: Intra-articular corticosteroid injection of betamethasone at the knee joint among patients with diabetes was associated with a significant increase in IR levels compared with baseline levels, 1 day following the injection. The mean percentage of increase in IR was higher than that for FBG levels.

The effect of local injection of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis among patients with greater trochanteric pain syndrome.

Greater trochanteric pain syndrome (GTPS) is a common clinical entity for which the most effective treatment is local corticosteroid injection (LCI). There are no studies on the effect of LCI among patients with GTPS on the hypothalamic-pituitary-adrenal axis. The present study recruited nonselected patients diagnosed with GTPS. After consenting, participants received low dose (1 µg) of adrenocorticotropin hormone (ACTH) stimulation test at 09:00. Immediately following the test, participants received a LCI of 80 mg of methylprednisolone acetate at the greater trochanteric region. The ACTH stimulation test was repeated 1, 2, 4, and 6 weeks following the LCI. Cortisol samples were obtained at just prior to (basal) and 30 min (post-stimulation) following every ACTH stimulation test. Serum cortisol levels of <500 µmol/l obtained 30 min following the ACTH stimulation test were considered evidence of secondary adrenal insufficiency. The study enrolled 22 patients, 21 of whom completed participation. There were 19 female participants (~90%), and mean age of all the participants was 55.2 ± 8.6 years. Four participants showed evidence of secondary adrenal insufficiency, which was observed only at weeks 1 and 2 following the LCI. Mean serum cortisol level among these four participants 30 min following the ACTH stimulation test was 354 µmol/l, with a range of 268-430 µmol/l. LCI of 80 mg of methylprednisolone acetate in the greater trochanteric area among patients with GTPS was associated with transient secondary adrenal insufficiency in ~20% of the patients, mainly 1 week following the injection.

The impact of intra-articular methylprednisolone acetate injection on fructosamine levels in diabetic patients with osteoarthritis of the knee, a case-control study.

Fructosamine is a glycated protein that reflects blood glucose control over the last 2-3 weeks. There are no studies that address the impact of intra-articular injection (IAI) of methylprednisolone acetate (MPA) on fructosamine levels among patients with type-2 diabetes and osteoarthritis of the knee (OAK). Non-selected patients attending the rheumatology or orthopedic clinic with type-2 diabetes and painful OAK, who failed non-steroidal anti-inflammatory drugs (NSAIDS) and physical therapy, were asked to participate in our study. After consent blood tests were drown for fructosamine, hemoglobin A1c (HbA1c) level, complete blood count, lipid profile, serum albumin, serum protein, c-reactive protein, and erythrocyte sedimentation rate. Demographic and different clinical parameters were also documented. Immediately after that, patients had IAI of 80 mg of MPA at the knee joint (group 1). Two to three weeks later, the same blood tests were repeated (except for HbA1c). Age- and sex-matched group of patients with type-2 diabetes and painful OAK attending the same clinics, but who were managed by NSAIDS were asked to participate as a control group (group 2) and had the same evaluation at enrollment and 2-3 weeks later, after consent. Eighteen patients from either group completed the study. Mean fructosamine level in group 1 patients was 263.7 ± 31.8 mg% prior to the IAI vs. 274.6 ± 39.3 mg% (p = 0.035), 2-3 weeks later, while mean fructosamine level in the control group (group 2) at enrollments was 274.2 ± 31.2 mg% vs. 269 ± 30.2 mg%, p = 0.509, 2-3 weeks later. There was no significant change in any other parameter tested at enrollment in either group, compared to those obtained 2-3 weeks afterwards. Body mass index was on the edge of significance as a predictor for a significant change in fructosamine level in group 1 patients. IAI of 80 mg of MPA in patients with type-2 diabetes and OAK had resulted in a significant, though mild increase in fructosamine levels 2-3 weeks later.

Effects of carnitine on oxidative stress response to intravenous iron administration to patients with CKD: impact of haptoglobin phenotype.

BACKGROUND: Anemia is a common disorder in CKD patients. It is largely attributed to decreased erythropoietin (EPO) production and iron deficiency. Therefore, besides EPO, therapy includes iron replenishment. However, the latter induces oxidative stress. Haptoglobin (Hp) protein is the main line of defense against the oxidative effects of Hemoglobin/Iron. There are 3 genotypes: 1-1, 2-1 and 2-2. Hp 2-2 protein is inferior to Hp 1-1 as antioxidant. So far, there is no evidence whether haptoglobin phenotype affects iron-induced oxidative stress in CKD patients. Therefore, the present study examines the influence of carnitine treatment on the intravenous iron administration (IVIR)-induced oxidative stress in CKD patients, and whether Hp phenotype affects this response. TRIAL REGISTRATION: Current Controlled Trials ISRCTN5700858. This study included 26 anemic (Hb = 10.23 ± 0.28) CKD patients (stages 3-4) that were given a weekly IVIR (Sodium ferric gluconate, [125 mg/100 ml] for 8 weeks, and during weeks 5-8 also received Carnitine (20 mg/kg, IV) prior to IVIR. Weekly blood samples were drawn before and after each IVIR for Hp phenotype, C-reactive protein (CRP), advanced oxidative protein products (AOPP), neutrophil gelatinase-associated lipocalin (NGAL), besides complete blood count and biochemical analyses. RESULTS: Eight percent of CKD patients were Hp1-1, 19 % Hp2-1, and 73 % Hp2-2. IVIR for 4 weeks did not increase hemoglobin levels, yet worsened the oxidative burden as was evident by elevated plasma levels of AOPP. The highest increase in AOPP was observed in Hp2-2 patients. Simultaneous administration of Carnitine with IVIR abolished the IVIR-induced oxidative stress as evident by preventing the elevations in AOPP and NGAL, preferentially in patients with Hp2-2 phenotype. CONCLUSIONS: This study demonstrates that Hp2-2 is a significant risk factor for IVIR-induced oxidative stress in CKD patients. Our finding, that co-administration of Carnitine with IVIR preferentially attenuates the adverse consequences of IVIR, suggests a role for Carnitine therapy in these patients.

The effect of intra-articular injection of Diprospan at the knee joint on the hypothalamic-pituitary-adrenal axis.

QUESTIONS UNDER STUDY: In this work we wanted to evaluate the effect of intra-articular injection (IAI) at the knee joint of 1 ml of Diprospan on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Consecutive patients attending the rheumatology or orthopaedic clinic with osteoarthritic knee pain not responding satisfactorily to medical and physical therapy were asked to participate in our study. After consent, patients had ultrasound-guided IAI of 1 ml of Diprospan, containing 2 mg of betamethasone sodium phosphate and 5 mg of betamethasone dipropionate. Demographic, clinical, laboratory and radiographic variables were documented. Just prior to the knee injection and 1, 2, 4 and 6 weeks later, patients had a 1-µg adrenocorticotropic hormone (ACTH) stimulation test. Secondary adrenal insufficiency (SAI) was defined as a poststimulation (30 minutes after ACTH injection) serum cortisol level of less than 18 µg/dl (~500 nmol/l) and lack of a rise of >6 µg/dl (~166 nmol/l) over the basal level in poststimulation serum cortisol. RESULTS: Twenty patients completed the study. There were 3 male and 17 female patients, with a mean age of 58.6±9.5 years. Six (30%) patients had evidence of SAI and in five of them it was seen at one time-point, mostly at week 2 after the IAI. In one patient, SAI was prolonged and observed from week 1 to week 4. CONCLUSIONS: IAI at the knee joint of 1 ml of Diprospan was associated with a transient high rate of SAI.

The impact of corticosteroid treatment on hemoglobin A1C levels among patients with type-2 diabetes with chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Corticosteroid-induced hyperglycemia is a known adverse effect. There are no studies on the impact of corticosteroid treatment on hemoglobin A1c (HbA1c) levels in type-2 diabetes patients with chronic obstructive pulmonary disease (COPD) exacerbation. METHODS: HbA1c levels were evaluated in type-2 diabetes patients with COPD exacerbation on admission to the hospital (group-1) and 3-months later. Demographic, clinical, laboratory variables and total steroid dose were documented. Age- and sex-matched group of type-2 diabetes patients with COPD who were admitted for other reasons (group-2), were asked to participate as a control group. Mann-Whitney and Chi square/Fischer's exact tests were used to compare between the parameters of the two groups. Wilcoxon's signed rank test was used to compare between HbA1c levels at baseline and 3 months later. Multi-variate linear regression analysis was used to find predictors for a change in HbA1c levels in group-1 patients. RESULTS: 23 and 21 patients in groups 1 and 2 respectively, completed the study. There were 39 male (∼89%) patients. Mean age of the patients was 66.2 ± 8.2 years. In both groups, anti-diabetic management was augmented. There was no significant change in the HbA1c levels in group-1 (p = 0.416), however there was a significant decrease in HbA1c levels in group-2 (p = 0.032). Total dose of steroids was a predictor for an increase in HbA1c levels in group-1 patients (p = 0.026). CONCLUSIONS: Type-2 diabetes patients who were treated with steroids for COPD exacerbation had no significant change in HbA1c levels. Total dose of steroids was a predictor for an increase in HbA1c levels.

Simultaneous bilateral knee injection of methylprednisolone acetate and the hypothalamic-pituitary adrenal axis: a single-blind case-control study.

OBJECTIVE: The objective of this study was to evaluate the effect of simultaneous bilateral intra-articular injection (IAI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal axis in patients with knee osteoarthritis. METHODS: Nonselected patients with symptomatic bilateral knee osteoarthritis had simultaneous IAI of 80 mg MPA at each knee (group 1). Just before the injection and on weeks 1, 2, 4, 6, and 8 after it, patients had 1 µg adrenocorticotropin hormone stimulation test. Age- and sex-matched patients had simultaneous IAI of 60 mg of hyaluronic acid in each knee (group 2) and the same protocol of adrenocorticotropin hormone stimulation tests. Demographic, clinical, and laboratory parameters were documented in all the patients. Secondary adrenal insufficiency (SAI) was defined as poststimulation serum cortisol levels of less than 18 µg/dL. RESULTS: Twenty patients were enrolled in each group. There were 15 women and 5 men in each group. Mean age of the patients in group 1 was 60.3 (SD, 7.6) years. Twelve patients (60%) from group 1 had evidence of SAI versus 3 patients in group 2 (P = 0.003). In all the patients who had SAI in group 1, it was observed in week 1 with decreasing frequency of SAI at the subsequent time points. Yet, 2 patients (10%) from group 1 had evidence of SAI 8 weeks after the IAI. Secondary adrenal insufficiency did not significantly correlate with any demographic, clinical, or laboratory parameter. CONCLUSIONS: Secondary adrenal insufficiency was very common following simultaneous bilateral IAI of 80 mg of MPA. Although it was transient, SAI could still be observed nearly 2 months after the IAI, in 10% of the patients.

Intra-articular methylprednisolone acetate injection at the knee joint and the hypothalamic-pituitary-adrenal axis: a randomized controlled study.

The objective of this study was to evaluate the effect of intra-articular corticosteroid injection (IACI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal (HPA) axis in patients with osteoarthritis of the knee. Patients with symptomatic osteoarthritis of the knee who failed to respond to nonsteroidal anti-inflammatory medications and physical therapy were randomized between group 1 and group 2. Group 1 patients had an IACI of 80 mg of MPA at the knee joint and group 2 patients had an intra-articular injection (IAI) of 6 ml (60 mg) of sodium hyaluronate (control group). Immediately prior to the IAI and on weeks 1, 2, 3, 4, and 8 following IAI, patients from both groups underwent a low-dose (1 µg) adrenocorticotropin hormone (ACTH) stimulation test. Demographic, clinical, laboratory, and radiologic variables were documented in all patients. Both criteria of <7 µg/dl increase in the serum cortisol level and absolute levels of <18 µg/dl 30 min following the ACTH stimulation test were used to define secondary adrenal insufficiency (SAI). Twenty patients were randomized in each group. In group 1, 25 % of patients had SAI vs. none in group 2 (p = 0.0471). The earliest SAI was observed at week 2, and latest SAI was observed at week 4. SAI was observed at one time point, two consecutive time points, or two separate time points in the same patient. There was no correlation between SAI and any of the demographic, clinical, or laboratory variables. An IACI of 80 mg MPA at the knee joint induced a transient SAI in 25 % of the patients, an effect that was observed between week 2 and week 4 following the IACI.

Anti-Candida albicans biofilm effect of novel heterocyclic compounds.

OBJECTIVES: The aims of this study were to develop new anti-biofilm drugs, examine their activity against Candida albicans biofilm and investigate their structure-activity relationship and mechanism of action. METHODS: A series of thiazolidinedione and succinimide derivatives were synthesized and their ability to inhibit C. albicans biofilm formation and destroy pre-formed biofilm was tested. The biofilms' structure, metabolic activity and viability were determined by XTT assay and propidium iodide and SYTO 9 live/dead stains combined with confocal microscopic analysis. The effect of the most active compounds on cell morphology, sterol distribution and cell wall morphology and composition was then determined by specific fluorescent stains and transmission electron microscopy. RESULTS: Most of the compounds were active at sub-MICs. Elongation of the aliphatic side chain resulted in reduced anti-biofilm activity and the sulphur atom contributed to biofilm killing, indicating a structure-activity relationship. The compounds differed in their effects on biofilm viability, yeast-to-hyphal form transition, hyphal morphology, cell wall morphology and composition, and sterol distribution. The most effective anti-biofilm compounds were the thiazolidinedione S8H and the succinimide NA8. CONCLUSIONS: We developed novel anti-biofilm agents that both inhibited and destroyed C. albicans biofilm. With some further development, these agents might be suitable for therapeutic purposes.

The effect of intra-articular injection of betamethasone acetate/betamethasone sodium phosphate at the knee joint on the hypothalamic-pituitary-adrenal axis: a case-controlled study.

BACKGROUND: Intra-articular corticosteroid injection (IACI) of betamethasone depot preparation is a popular procedure at the knee joint. Intra-articular corticosteroid injection in general could be associated with systemic effects including suppression of the hypothalamic-pituitary-adrenal axis. There are nearly no reports on the effect of IACI of betamethasone at the knee joint on the hypothalamic-pituitary-adrenal axis. METHOD: Consecutive patients attending the rheumatology or orthopedic clinic with osteoarthritic knee pain who were not responding satisfactorily to medical and physical therapy were allocated to group 1 after consent and given IACI of 6 mg of betamethasone acetate/betamethasone sodium phosphate. After completion of this part, consecutive age- and sex-matched patients were allocated to group 2 and given intra-articular injection of 60 mg of sodium hyaluronate. Demographic, clinical, laboratory, and radiographic variables were documented. Just before the knee injection and 1, 2, 3, 4, and 8 weeks later, patients had 1-µg adrenocorticotropin hormone (ACTH) stimulation test. Secondary adrenal insufficiency (SAI) was defined as levels of less than 18 µg/dL and lack of a rise of more than 6 µg/dL in serum cortisol level, 30 minutes after the ACTH stimulation test.Patients were blinded to the injected material, and all injections were ultrasound guided. RESULTS: Twenty patients were enrolled in each group and equally divided between the 2 sexes. The mean age of the patients was approximately 54 years in both groups. No significant difference in any variable was seen between the 2 groups. One patient only from group 1 (the betamethasone group) had SAI 3 weeks after the IACI compared to none in the control group (P > 0.9999). His serum cortisol level 30 minutes after the ACTH stimulation was 17 µg/dL, with a rise of 3 µg/dL from baseline. CONCLUSION: Intra-articular corticosteroid injection of 6 mg of betamethasone acetate/betamethasone sodium phosphate at the knee joint was not significantly associated with SAI at the time points tested.

The effect of epidural methylprednisolone acetate injection on the hypothalamic-pituitary-adrenal axis.

STUDY OBJECTIVE: To evaluate the effect of an epidural corticosteroid injection of 80 mg and 40 mg of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis and on back pain. DESIGN: Randomized, single-blinded prospective study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 42 patients with low back pain due to radiculopathy. INTERVENTIONS: Group 1 received an epidural corticosteroid injection of 80 mg of methylprednisolone acetate, and Group 2 received an epidural corticosteroid injection of 40 mg of methylprednisolone acetate. All study patients underwent a stimulation test of one µg of adrenocorticotropin hormone (ACTH), and their pain levels were graded just prior to and following the epidural corticosteroid injection on weeks one, 3, and 4. MEASUREMENTS: Serum cortisol of the ACTH stimulation tests and back pain levels were rated using a visual analog scale (VAS). Serum cortisol levels lower than 18 ng/mL 30 minutes following the ACTH stimulation test were considered to be secondary adrenal insufficiency. MAIN RESULTS: 21 patients were enrolled in each group. The rate of secondary adrenal insufficiency in Group 1 was ~86%, ~ 22%, and ~17% of patients versus ~53% (P = 0.024), 15% (P = 0.874), and ~12% (P = 0.715) of Group 2 patients at weeks one, 3, and 4, respectively. About 62%, 56%, and 39% of Group 1 patients had a favorable clinical response as opposed to ~47% (P = 0362), 35% (P = 0.21), and ~6% (P = 0.049) of Group 2 patients at weeks one, 3, and 4, respectively. CONCLUSIONS: Epidural corticosteroid injection of methylprednisolone acetate in both groups was associated with very high rates of secondary adrenal insufficiency, but significantly more so in Group 1 at week one. This suppression was transient, with recovery of the gland in most patients noted over the ensuing weeks. An epidural corticosteroid injection of 80 mg had higher rates of favorable clinical response than a 40 mg injection, but significantly more so at week 4 only. This favorable response waned over a few weeks in both groups.

Acute kidney injury following isotretinoin treatment.

PATIENT: Female, 17 FINAL DIAGNOSIS: Acute kidney injury Symptoms: Flank pain • nausea • vomiting MEDICATION: Isotretinoin Clinical Procedure: Acne treatment Specialty: Nephrology Objective: Unknown etiology. BACKGROUND: Isotretinoin is widely used for the treatment of acne that is unresponsive to topical therapy. Despite its efficacy, isotretinoin has various adverse effects, including cheilitis, increased risk of cutaneous Staphylococcus aureus infections, and liver function abnormalities. CASE REPORT: A 17-years-old female was admitted to the hospital with a 5-day history of bilateral flank pain, nausea and vomiting. On physical examination, acne was observed over her face treated with Isotretinoin. Both vital signs and physical examination were normal apart from tenderness over both flanks. Initial laboratory results revealed serum creatinine of 2 mg/dl, blood urea nitrogen 20 mg/dl. Complete blood count, full chemistry panel, complements and urinalysis were all normal. Twenty four hours urine collection showed creatinine clearance test of 33 ml/min and urine protein of 390 mg/day. Chest X-ray and ultra sound of kidneys were normal. Acute kidney injury was suspected and she was treated with intravenous fluids. Despite these measures her kidney function steadily worsened. Her serum creatinine on days 2 and 3 were 2.16 and 2.24 mg/dl, respectively. Wright's staining for eosinophils was positive. Fortunately her serum creatinine started to decrease and was 2 mg/dl and 1.4 mg/dl by day 4 and 5, respectively. A tentative diagnosis of acute interstitial nephritis due to Isotretinoin was made, with the recommendation to avoid this treatment in the future. Two weeks later her serum creatinine and urinary protein returned to normal values. CONCLUSIONS: Flank pain should raise suspicion of Isotretinoin-induced acute kidney injury, suggesting that a careful kidney function test besides testing for liver function is warranted in patients with these symptoms.

Major depressive disorders in chronic hemodialysis patients in Nazareth: identification and assessment.

OBJECTIVE: Depression illnesses are commonly observed in hemodialysis (HD) patients, which can influence the quality of life of end-stage renal disease patients. We evaluate the prevalence and predictive risk factors of depression in the Arab population undergoing HD in Nazareth, Israel. METHODS: We conducted a prospective study that included 71 patients in the HD unit with a mean age of 61.9 ± 14.13 years who had undergone HD and 26 healthy control subjects with a mean age of 59.3 ± 7.3. Beck's Depression Inventory and Hamilton Depression Scale assessments were administered. Blood analysis for hematological and biochemical parameters was obtained. Diagnosis was made using the Diagnostic and Statistical Manual of Mental Disorders scale to correlate psychological variables with clinical, hematological, and biochemical parameters. Statistical analysis was carried out using analysis of variance followed by Tukey post-hoc multiple comparison tests. RESULTS: The prevalence of depression was 43.7% in HD patients. Between HD patients and controls, cortisol values were 16.96 ± 0.5476 and 11.96 ± 1.116, respectively (P < 0.0001; 95% confidence intervals [CI]: 2.416-6.825). Between depressed HD patients versus control subjects, cortisol values were 16.48 ± 0.72 and 11.96 ± 1.116, respectively (P = 0.0013; 95% CI: 1.878-7.184). Hematological and biochemical parameters were compared between depressed HD and nondepressed patients, but differences between the two groups were found to be insignificant (P > 0.05). CONCLUSION: Our HD patients were severely depressed. Studies of glucocorticoid turnover activity such as cortisol, a potent chemical stress hormone, may be used as a model and marker for early diagnosis of depression among HD patients. The strong familial support system in Arabic traditions has failed to decrease depression among these patients.