Prevalence and factors associated with sputum smear non-conversion after two months of tuberculosis treatment among smear-positive pulmonary tuberculosis patients in Rwanda: a cross-sectional study.

BACKGROUND: Non-conversion of sputum smear prolongs the infectivity of pulmonary tuberculosis patients and has been associated with unfavorable tuberculosis (TB) treatment outcomes. Nevertheless, there is a limited evidence on predictors of sputum smear non-conversion among smear-positive PTB (SPPTB) patients in Rwanda. Therefore, this study aimed to determine the factors associated with sputum smear non-conversion after two months of treatment among SPPTB patients in Rwanda. METHODS: A cross-sectional study was conducted among SPPTB patients registered in the national electronic TB reporting system by all health facilities countrywide (Rwanda) from July 2019 to June 2021. Eligible patients who had completed the first two months of anti-TB treatment and with smear results at the end of the second month of treatment were included in the study. Bivariate and multivariate logistic regression analyses were done using STATA version 16 to determine the factors associated with sputum smear non-conversion. Adjusted odds ratio (OR), 95% confidence interval (CI), and p-value < 0.05 was considered statistically significant. RESULTS: This study included 7,211 patients. Of them, 632 (9%) patients had sputum smear non-conversion at the end of the second month of treatment. In multivariate logistic regression analysis, age groups of 20-39 years (AOR = 1.7, 95% CI: 1.0-2.8) and 40-59 years (AOR:2, 95% CI: 1.1-3.3), history of first-line TB treatment failure (AOR = 2, 95% CI: 1.1-3.6), follow-up by community health workers(CHWs) (AOR = 1.2, 95% CI: 1.0-1.5), BMI < 18.5 at TB treatment initiation (AOR = 1.5, 95% CI: 1.2-1.8), and living in Northern Province of Rwanda (AOR = 1.4, 95% CI: 1.0-2.0), were found to be significantly associated with sputum smear non-conversion after two months of treatment. CONCLUSION: Sputum smear non-conversion among SPPTB patients remains low in Rwanda compared to countries of similar health care setting. Identified risk factors for sputum smear non-conversion among SPPTB patients in Rwanda were age (20-39 years, 40-59 years), history of first-line TB treatment failure, follow up by CHWs, BMI < 18.5 at TB treatment initiation and residence (Northern province).

Nosocomial BK Polyomavirus Infection Causing Hemorrhagic Cystitis Among Patients With Hematological Malignancies After Hematopoietic Stem Cell Transplantation.

BK polyomavirus (BKPyV) is recognized as a pathogen that causes diseases such as hemorrhagic cystitis and nephritis after allogeneic hematopoietic stem cell transplantation (HSCT) or renal transplantation. BKPyV-associated disease is thought to occur through reactivation under immunosuppression. However, the possibility of its nosocomial transmission and the clinical significance of such transmission have not been elucidated. During a 6-month period, nine adult patients (median age: 47 years) who had hematological disorders and who were treated with HSCT (n = 7) or chemotherapy (n = 2) in a single hematology department developed hemorrhagic cystitis due to BKPyV infection. The polymerase chain reaction products of BKPyV DNA obtained from each patient were sequenced. Of the nine patients, six had subtype I, 2 had subtype IV, and 1 had subtype II or III. In the alignment of sequences, four and two of the six subtype I strains were completely homologous (100%). These results strongly suggest that BKPyV has the potential to cause nosocomial infection within a medical facility, especially among recipients of HSCT. Further studies are clearly warranted to elucidate the route(s) of BKPyV transmission in order to establish optimal infection control.

Life-Long Wheel Running Attenuates Age-Related Fiber Loss in the Plantaris Muscle of Mice: a Pilot Study.

The purpose of this study was to investigate whether long-term wheel running would attenuate age-related loss of muscle fiber. Male ICR mice were divided into young (Y, n=12, aged 3 months), old-sedentary (OS, n=5, aged 24 months), and old-exercise (OE, n=6, aged 24 months) groups. The OE group started spontaneous wheel running at 3 months and continued until 24 months of age. Soleus and plantaris muscles were fixed in 4% paraformaldehyde buffer. The fixed muscle was digested in a 50% NaOH solution to isolate single fiber and then fiber number was quantified. The masses of the soleus and plantaris muscles were significantly lower at 24 months than at 3 months of age, and this age-related difference was attenuated by wheel running (P<0.05). Soleus muscle fiber number did not differ among the groups. In the plantaris muscle, the fiber number in the OS group (1 288±92 fibers) was significantly lower than in the Y group (1 874±93 fibers), and this decrease was attenuated in the OE group (1 591±80 fibers) (P<0.05). These results suggest that age-related fiber loss occurs only in the fast-twitch fiber-rich muscle of mice, and that life-long wheel running exercise can prevent this fiber loss.

Post-transplant lymphoproliferative disorder of the adrenal gland after allogeneic hematopoietic stem cell transplantation: report of two cases and literature review.

Post-transplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced-stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV-associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.

Fucosylated TGF-ß receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells.

BACKGROUND: Transforming growth factor-ß (TGF-ß) is a major inducer of epithelial-mesenchymal transition (EMT) in different cell types. TGF-ß-mediated EMT is thought to contribute to tumour cell spread and metastasis. Sialyl Lewis antigens synthesised by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilised as tumour markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-ß is unclear. METHODS: Colorectal cancer cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion and migration assays. The expression and phosphorylation status of TGF-ß downstream molecules were analysed by western blot. Fucosylation of TGF-ß receptor (TßR) was examined by lectin blot analysis. RESULTS: Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TßR and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT. CONCLUSION: Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF-ß-mediated EMT.

Osteoprotegerin is secreted into the coronary circulation: a possible association with the renin-angiotensin system and cardiac hypertrophy.

The circulating osteoprotegerin (OPG) level reflects a series of cardiovascular diseases; however, the source(s) of circulating OPG remain(s) to be determined. This study explored whether OPG is released in the coronary circulation and whether it is associated with cardiac structure and function. Fifty-six patients (67±10 years old, male 57%, hypertension 73%, coronary artery disease 50%) were enrolled, and blood samples were collected simultaneously from the orifice of the left coronary artery (CA) and the coronary sinus (CS) after angiography. The concentration of OPG was higher in the CS than in the CA (7.7±4.1 vs. 6.7±3.6 pmol/l, p<0.001). The trans-cardiac OPG concentration was significantly (p=0.019) decreased in patients who have been prescribed either an angiotensin converting enzyme inhibitor or an angiotensin II type 1 receptor blocker (ACEI/ARB). In patients subgroup who did not take an ACEI/ARB (n=27), the trans-cardiac OPG level was positively correlated with age (r=0.396, p=0.041) and relative wall thickness of left ventricle (r=0.534, p=0.004). In multivariate linear regression analysis, relative wall thickness remained to be the independent variable for the trans-cardiac OPG level (p=0.004). Moreover, trans-cardiac OPG was significantly (p=0.021) increased in patients with relative wall thickness greater than 0.45 but it did not differ if the left ventricular mass index was increased (≥116 for males, or ≥ 104 for females, g/m(2)) or not (p=0.627). This study suggests that OPG is secreted into the coronary circulation and is associated with concentric remodeling/hypertrophy of LV, possibly in interactions with the renin-angiotensin system.

Nephrotoxicity of concomitant use of tacrolimus and teicoplanin in allogeneic hematopoietic stem cell transplant recipients.

Both tacrolimus and glycopeptide antibiotics are known to be nephrotoxic, and are often concomitantly given after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. The aim of this study is to evaluate the nephrotoxicity of concomitant use of tacrolimus and glycopeptide antibiotics in HSCT recipients. We retrospectively evaluated 67 patients who received intravenous tacrolimus and teicoplanin concomitantly for >4 days after allogeneic HSCT for hematologic diseases. Therapeutic drug monitoring (TDM) was performed in all patients for both tacrolimus and teicoplanin. The median age of the patients was 48 years (range: 16-62), and the median duration of the co-administration of tacrolimus and teicoplanin was 11 days (range: 4-40). The mean serum creatinine (sCr) level tended to be elevated after the co-administration (from 0.69 ± 0.26 to 0.75 ± 0.30 mg/dL; P = 0.08); however, a 2-fold or greater increase in sCr was observed only in 2 (3.0%) patients. Increased sCr was reversible, and no patient required hemodialysis. These results suggest that the incidence of clinically significant nephrotoxicity can be minimized if the TDM of each drug is properly applied.

The effect of prescription patterns on the performance of the pharmacy department of a Regional Referral Hospital, Uganda.

Background: Poor drug prescription patterns (PP) result in irrational medicine use, avoidable stock outs and drug expiries. Objective: This study primarily assessed the effects of PP on the performance of the pharmacy department (PD) of Mbarara Regional Referral Hospital (MRRH) Uganda. Methods: This was a mixed method cross-sectional study conducted in the outpatient department (OPD) of MRRH, questionnaires were administered to 86 prescribers and 300 patient prescriptions were reviewed. Ethical clearance was granted and informed consent of patients. Data were analysed, presented in the form of graphs, tables. Results: The overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officersThe overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officers. Conclusion: Prescription pattern affected the performance of the PD of MRRH, calling for its continued monitoring to ensure that guidelines are upheld, EML and UCG are availed and utilized.

Persistent parvovirus B19 infection resulting in red cell aplasia after allogeneic hematopoietic stem cell transplantation.

Persistent parvovirus B19 (PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patient's family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic.

Antagonistic effect of flumazenil after midazolam sedation on arterial-cardiac baroreflex.

BACKGROUND: Flumazenil is generally administered to antagonise the sedative effect of midazolam. However, although flumazenil completely antagonises the sedative effect of midazolam, a few effects remain unantagonised. Hence, it is unclear whether flumazenil restores the attenuation of the arterial-cardiac baroreflex (i.e. arterial-heart rate reflex) induced by midazolam. We investigated the antagonistic effect of flumazenil administered after midazolam on cardiac baroreflex, to reveal whether complete recovery from midazolam-induced sedation by flumazenil administration is accompanied by restoration of midazolam's attenuating effects on the cardiac baroreflex. METHOD: Twelve healthy male subjects received midazolam followed by flumazenil until complete recovery from midazolam sedation. Before and during midazolam sedation, and after flumazenil administration, cardiac baroreflex function was assessed by sequence analysis and transfer function analysis between spontaneous oscillations in systolic arterial pressure and R-R interval. RESULTS: During midazolam sedation, defined by an Observer's Assessment of Alertness/Sedation scale score of 3, BIS value decreased significantly. Simultaneously, the baroreflex indices of the two analyses decreased significantly compared with baseline, suggesting attenuated cardiac baroreflex function. With complete recovery from midazolam sedation by flumazenil, indicated by an Observer's Assessment of Alertness/Sedation scale score of 5, BIS values returned to the baseline level. Simultaneously, cardiac baroreflex indices also returned to baseline levels. CONCLUSION: The present results suggest that complete recovery from midazolam sedation by flumazenil is accompanied by restoration of the attenuated cardiac baroreflex function induced by midazolam.

Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.

Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft-versus-host disease requiring high-dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species.

The effects of age on maintenance of intense neuromuscular block with rocuronium.

BACKGROUND: Increasing age is associated with a longer duration of action of neuromuscular block. The aim of this study was to determine the influence of ageing on the recovery of the post-tetanic count (PTC) from rocuronium-induced neuromuscular block. METHODS: Twenty-two younger (20-60 years) and 22 older (> 70 years) patients were enrolled in this study. After induction of anaesthesia with fentanyl and propofol, all patients initially received 1 mg/kg rocuronium and neuromuscular block were evaluated by contractions of the adductor pollicis muscle to ulnar nerve train-of-four stimulation using an acceleromyograph. Subsequently, intense rocuronium-induced block was determined every 6 min using the PTC during 1.0-1.5% sevoflurane and remifentanil anaesthesia. When the first response to the PTC stimulus was detected, 0.2 mg/kg rocuronium was additionally administered, and again, spontaneous recovery of neuromuscular function was monitored until the first response to the PTC reappeared. RESULTS: Median values (range) of the times from the administration of 1 mg/kg and 0.2 mg/kg rocuronium until recovery of the first detectable PTC were significantly longer in the older [51.0 (27-100) min, P < 0.0001 and 30.0 (12-66) min, P = 0.0036, respectively] than the younger patients [31.5 (21-45) min and 18.0 (12-36) min, respectively]. CONCLUSION: The times from rocuronium injection to reappearance of the first response to PTC stimulation are approximately twofold longer and more variable in older than younger patients. Hence, the dosing interval of rocuronium should be adjusted using neuromuscular monitoring when maintaining intense neuromuscular block, especially in older patients.

Increase of coagulation potential in chronic spontaneous urticaria.

BACKGROUND: The pathogenesis of chronic spontaneous urticaria (CU) has recently been conceived to be associated with thrombin generation through the extrinsic coagulation pathway. However, little is known about the components of the intrinsic coagulation pathway potentially involved. METHODS: To investigate the whole process of coagulation, both classical coagulation assays and a global coagulation test, the intrinsic coagulation pathway-dependent activated partial thromboplastin time (APTT) clot waveform analysis, were performed using plasma of 36 patients with CU who had various severities. RESULTS: Classical coagulation assays revealed that levels of fibrinogen, D-dimer, and fibrin and fibrinogen degradation products (FDP), and positive rates of soluble fibrin monomer complex (SFMC) were significantly elevated in patients with CU, whereas the elevation of prothrombin fragment 1 + 2 was not statistically significant. On the other hand, all parameters of a global coagulation test, APTT clot waveform analysis, evidently showed a hypercoagulable pattern and were significantly correlated to disease severity of CU. CONCLUSIONS: CU is characterized by elevated blood coagulation potential with involvement of the intrinsic coagulation factors, which may contribute in vivo to the generation of fibrin even by small amounts of thrombin.

Bispectral index is related to the spread of spinal sensory block in patients with combined spinal and general anaesthesia.

BACKGROUND: A relationship between the depth of sedation as measured by the bispectral index (BIS) and spinal sensory block height in patients with light to no additional sedation has been described previously. The present study was designed to investigate the hypothesis that BIS values closely correlate with the spread of spinal sensory block in patients deeply sedated with an i.v. target-controlled infusion of propofol. METHODS: Subjects comprised 100 patients aged 20-64 yr and undergoing arthroscopic knee surgery. Patients were given spinal anaesthesia with bupivacaine 0.5% (3 ml). Propofol was administered to achieve a target effect-site concentration of 3.0 µg ml⁻¹. The relationship between the spinal sensory level at 15 min after spinal anaesthesia and BIS values during 1-5, 6-10, 11-15, and 16-20 min time intervals after the estimated effect-site concentration reached 3.0 µg ml⁻¹ was evaluated. RESULTS: The sensory level of spinal analgesia significantly and strongly correlated with BIS values during each time period after the estimated effect-site concentration remained at 3.0 µg ml⁻¹ (P<0.0001). The correlation coefficient values were 0.8 during 1-5 min, 0.844 during 6-10 min, 0.801 during 11-15 min, and 0.804 during 16-20 min time periods. CONCLUSIONS: We demonstrated that BIS values significantly correlate with the level of spinal sensory block under deep sedation with propofol. The depth of sedation induced by spinal anaesthesia depends on the spread of spinal sensory block.

Reversibility of rocuronium-induced profound neuromuscular block with sugammadex in younger and older patients.

BACKGROUND: This study compared the reversibility of rocuronium-induced profound neuromuscular block with sugammadex in younger and older patients. METHODS: Fifteen younger (20-50 yr) and 15 older (≥70 yr) patients were sequentially enrolled in this study. After induction of anaesthesia and laryngeal mask insertion, contraction of the adductor pollicis muscle in response to ulnar nerve stimulation was quantified using acceleromyography during 1.0-1.5% end-tidal sevoflurane and remifentanil anaesthesia. All patients initially received rocuronium 1 mg kg(-1), followed by 0.02 mg kg(-1) when a post-tetanic count (PTC) of 1 or 2 was observed. After completion of surgery, at reappearance of 1-2 PTC, the time required for a single bolus dose of 4 mg kg(-1) sugammadex to produce recovery to a train-of-four (TOF) ratio of 0.9 was recorded. RESULTS: There were no differences in the total dose of rocuronium administered between the younger [mean (sd): 93.4 (17.5) mg] and the older [97.5 (32.2) mg] groups. In all patients, adequate recovery of the TOF ratio to 0.9 was achieved after administration of sugammadex, although it was significantly slower in the older [3.6 (0.7) min, P<0.0001] than in the younger group [1.3 (0.3) min]. There were no clinical events attributable to recurarization. CONCLUSIONS: Sugammadex can adequately restore neuromuscular function in older patients, although a longer time is required to recover from profound rocuronium-induced neuromuscular block than in younger patients.

Altered immunoglobulin A and M levels associated with changes in BAFF and APRIL after administration of intravenous immunoglobulin to treat Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of unknown etiology. Immunoregulatory abnormalities have been thought to contribute to its pathogenesis. Although treatment with intravenous immunoglobulin (IVIG) effectively prevents significant cardiac morbidity, the mechanism by which IVIG produces an effect in KD has yet to be fully elucidated. OBJECTIVE: To investigate the effects of IVIG on the immune system of patients with KD. PATIENTS AND METHODS: Eleven patients with KD (mean [SD] age, 2.2 [1.5] years) were enrolled in this prospective study and treated with high-dose IVIG therapy (2 g/kg in 1 or 2 infusions) during the acute phase of the disease. We examined immunological changes, with special reference to Ig levels and 2 previously unassessed cytokines: B cell-activating factor belonging to the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL). RESULTS: Clinical symptoms disappeared quickly in all cases, with no coronary artery abnormalities. IgA and IgM levels responded more rapidly than previously reported and reached a peak between the 3rd and 10th day after the start of IVIG treatment. The mean (SD) BAFF level was high before IVIG treatment (3234 [1904] pg/mL) and decreased significantly (1085 [257] pg/mL) after IVIG treatment, whereas the mean (SD) APRIL level before IVIG treatment (18.0 [10.0] ng/mL) rose significantly (120.6 [41.2] ng/mL). A significant inverse correlation between BAFF and APRIL was observed in patients with KD. CONCLUSIONS: These results suggest that IVIG may affect the pathogenesis of KD through alteration of BAFF/APRIL.

Eight calves cloned from somatic cells of a single adult.

Eight calves were derived from differentiated cells of a single adult cow, five from cumulus cells and three from oviductal cells out of 10 embryos transferred to surrogate cows (80 percent success). All calves were visibly normal, but four died at or soon after birth from environmental causes, and postmortem analysis revealed no abnormality. These results show that bovine cumulus and oviductal epithelial cells of the adult have the genetic content to direct the development of newborn calves.

Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli.

Inorganic polyphosphate (polyP), a polymer of hundreds of phosphate (Pi) residues, accumulates in Escherichia coli in response to stresses, including amino acid starvation. Here we show that the adenosine 5'-triphosphate-dependent protease Lon formed a complex with polyP and degraded most of the ribosomal proteins, including S2, L9, and L13. Purified S2 also bound to polyP and formed a complex with Lon in the presence of polyP. Thus, polyP may promote ribosomal protein degradation by the Lon protease, thereby supplying the amino acids needed to respond to starvation.

Transmission of chromosomally integrated human herpesvirsus 6 (HHV-6) variant A from a parent to children leading to misdiagnosis of active HHV-6 infection.

Only a handful of cases of chromosomally integrated human herpesvirus 6 (CI-HHV-6) have been reported, suggesting that this phenomenon is rare. We here present a familial case of HHV-6 variant A (HHV-6A) transmission through a generation, which was identified in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). A 31-year-old man with myelodysplastic syndrome underwent allogeneic HSCT from a human leukocyte antigen-identical sibling, and was found to be continuously yielding high copy numbers of HHV-6A DNA in plasma evaluated by real-time polymerase chain reaction (PCR). Antiviral therapy with ganciclovir or foscarnet failed to decrease the copy numbers. HHV-6A DNA was detected in the patient's buccal mucosa and hair follicles, and was also detected in the plasma, whole blood, and buccal mucosa of the patient's father and 2 siblings, but not in his mother. The sequences of HHV-6A DNA isolated from all family members were identical. Since monitoring of HHV-6 by PCR has been widely introduced to the field of HSCT, transplant physicians should be aware of such an alternative form of HHV-6 transmission, particularly when HHV-6A is detected.