Operative Epidemiology of the First Five Years in a New African Neurosurgery Training Center: The Experience in Rural Kenya at Tenwek Hospital 2016 to 2021.

BACKGROUND: One strategy to increase the availability of neurosurgical services in underserved regions within Sub-Saharan African countries is to create new residency training programs outside of cosmopolitan cities where programs may already exist. In 2016 Tenwek Hospital in rural western Kenya began offering full-time neurosurgical services and in 2020 inaugurated a residency training program. This review highlights the operative epidemiology of the first 5 years of the hospital's neurosurgical department. METHODS: A retrospective review of all cases performed by a neurosurgeon at Tenwek Hospital between September 2016 and February 2022 was performed. Patient demographics, surgical indications, length of stay, and in-hospital mortality rates were collected. RESULTS: A total of 1756 cases were retrievable. Of these, 1006 (57.3%) were male and mean age was 30 years (range 1 day to 97 years). Mean length of stay was 11 ± 2 days and in-hospital mortality rate was 4.4% (77 patients). The most common pathologies in children comprised hydrocephalus and spina bifida (42.5% and 21.1%, respectively); in adults, cranial trauma (28.2%), oncology (25.2%), and degenerative spine (18.5%) were most common. Trauma was the leading cause of death. CONCLUSIONS: The neurosurgical caseload of a rural hospital in an underserved area can provide not only an adequate neurosurgical volume, but a robust and varied exposure that is necessary for training safe and competent surgeons who are willing to remain in their countries of origin.

Skull base angiomatous leiomyoma: a case report and review of literature.

Leiomyomas, benign neoplasms of mesenchymal origin, are common in gastrointestinal and genitourinary tracts. They are comprised of well-differentiated smooth muscle cells with few mitotic figures. Leiomyomas should not exhibit metastatic potential, though metastasis has been reported. Primary intracranial lesions remain rare. Only 4 cases have been reported in immunocompetent patients. Here we report an intracranial leiomyoma in an immunocompetent patient. A 60 year-old woman with unremarkable past medical history presented with a right sixth nerve palsy. On examination, there was a right sixth nerve palsy with numbness over the right V2 and V3 areas. CT scan showed a well-defined lesion within the right middle cranial fossa adjacent to the cavernous sinus with bony remodelling of the lateral wall of the sphenoid sinus and greater wing of the right sphenoid. MRI showed extra axial mass lesion arising from the right Meckel´s cave/cavernous sinus. The lesion was T2 hyperintense and T1 isointense. Homogenously enhancing centrally with little enhancement peripherally. CT CAP showed no primary lesions. Differential diagnosis at that stage was between meningioma, schwannoma or metastasis. The patient underwent craniotomy and debulking of tumour. Histological analysis confirmed leiomyoma. Post-operative MRI showed residual enhancement in the region of Meckel's cave. As residual tumour was significant, the patient underwent STRS. Further MRI at 1 year showed regression of the tumour. Majority of intracranial leiomyomas are discovered in immunocompromised patients incidentally. Histology reveals spindle shaped cells with blunt ends and few mitotic figures. The best treatment option to date for primary intracranial leiomyomas remains surgical gross total resection without adjuvant radiation therapy. Intracranial leiomyoma transitioning to leiomyosarcoma post radiotherapy has been reported before and therefore follow up with serial imaging is warranted.

Long-term safety of gamma knife radiosurgery (SRS) for acromegaly.

PURPOSE: Acromegaly has high morbidity and mortality when growth hormone secretion remains uncontrolled. Stereotactic radiosurgery (SRS) may be used when pituitary surgery is not suitable or unsuccessful, but there are few very long-term safety data available, especially for significant adverse events such as stroke. METHODS: 118 patients with acromegaly were treated with SRS between 1985 and 2015, at the National Centre for Stereotactic Radiosurgery, Sheffield, UK. Data were gathered from case notes, hospital databases, and patient questionnaires. Stroke incidence in comparison to the normal population was quantified using the standardised incidence ratio (SIR), and visual complications assessed. RESULTS: 88% (104/118) had complete morbidity follow up data for analysis. The mean follow-up was 134 months, and median SRS dose was 30 Gy. 81% of tumours had cavernous sinus invasion. There was no excess stroke rate relative to that seen in two age- and sex-matched large population studies (SIR = 1.36, 95% CI 0.27-3.96; SIR = 0.52, 95% CI 0.06-1.89). In 68/104 patients who had MRI-guided SRS with no further radiation treatment (SRS or fractionated radiotherapy) there was no loss of visual acuity and 3% developed ophthalmoplegia. There was a positive correlation between > 1 radiation treatment and both ophthalmoplegia and worsening visual acuity. CONCLUSION: Stroke rate is not increased by SRS for acromegaly. Accurate MRI-based treatment planning and single SRS treatment allow the lowest complication rates. More than one radiation treatment (SRS or fractionated radiotherapy) was associated with increased visual complications.

The Amino Acid Changes T55A, A273P and R277C in the Beta-Lactamase CTX-M-14 Render E. coli Resistant to the Antibiotic Nitrofurantoin, a First-Line Treatment of Urinary Tract Infections.

The antibiotic nitrofurantoin is a furan flanked by a nitro group and a hydantoin ring. It is used to treat lower urinary tract infections (UTIs) that have a lifetime incidence of 50-60% in adult women. UTIs are typically caused by uropathogenic Escherichia coli (UPEC), which are increasingly expressing extended-spectrum beta-lactamases (ESBL), rendering them multi-drug resistant. Nitrofurantoin is a first-line treatment for gram-negative ESBL-positive UTI patients, given that resistance to it is still rare (0% to 4.4%). Multiplex PCR of ß-lactamase genes of the blaCTX-M groups 1, 2, 9 and 8/25 from ESBL-positive UTI patients treated at three referral hospitals in North Wales (UK) revealed the presence of a novel CTX-M-14-like gene harbouring the missense mutations T55A, A273P and R277C. While R277 is close to the active site, T55 and A273 are both located in external loops. Recombinant expression of CTX-M-14 and the mutated CTX-M-14 in the periplasm of E. coli revealed a significant increase in the Minimum Inhibitory Concentration (MIC) for nitrofurantoin from ≥6 µg/mL (CTX-M-14) to ≥512 µg/mL (mutated CTX-M-14). Consistent with this finding, the mutated CTX-M protein hydrolysed nitrofurantoin in a cell-free assay. Detection of a novel nitrofurantoin resistance gene indicates an emerging clinical problem in the treatment of gram-negative ESBL-positive UTI patients.

Comparison of Navigated versus Fluoroscopic-Guided Pedicle Screw Placement Accuracy and Complication Rate.

OBJECTIVES: Accurate placement of the pedicle screw is requisite for any successful spinal instrumentation procedure. Screw insertion can be achieved using free-hand and fluoroscopic- or navigation-guided techniques. We sought to assess the variation in accuracy between fluoroscopic- and navigation-guided techniques, which are both used in Sheffield Teaching Hospitals National Health Service Trust, a tertiary spine referral center. METHODS: Using a retrospective study design, we assessed all the pedicle screws placed between 2013 and 2018. Radiographic and clinical assessment of all cases was performed. RESULTS: We studied 176 spinal instrumented cases, with a total of 831 screws implanted, out of which 296 (35.6%) were navigated and 535 (64.4%) were fluoroscopic guided. Pathology treated included spinal stenosis, spondylolisthesis, tumors, and trauma. Suboptimal screw position was identified in 2.03% (n = 6) of the navigation-guided series and 4.11% (n = 22) of the fluoroscopic-guided series with an overall screw misplacement rate of 3.4%. Evaluating surgeons' individual accuracy rates revealed that suboptimal screw placement registered a higher variation for the fluoroscopy-guided technique, and the misplacement rate was higher for surgeons with a lower volume of cases. CONCLUSIONS: Use of navigation during spinal instrumentation helps lower the rate of screw misplacement for spinal surgeons who are at the beginning of their learning curve or do not frequently perform this kind of procedure. Navigation-guided spinal instrumentation is more accurate compared with fluoroscopic-guided techniques and appears to have a lower complication rate.

ITTREAT (Integrated Community Test - Stage - TREAT) Hepatitis C service for people who use drugs: Real-world outcomes.

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) provide an unprecedented opportunity for a "find-and-treat strategy." We aimed to report real-world clinical, patient reported and health economic outcomes of community-based hepatitis C virus (HCV) screening/treatment in people who use drugs (PWUDs). METHODS: Project ITTREAT (2013-2021), established at a drug and alcohol treatment centre, offered a comprehensive service. Generic (SF-12v2 and EQ-5D-5L) and liver-specific (SFLDQoL) health-related quality of life (HRQoL) were assessed before and after HCV treatment. Costs/case detected and cured were calculated. Primary outcome measure was sustained virological response (SVR) (intention to treat). RESULTS: Till March 2018, 573 individuals recruited, 462 (81%) males, mean age 40.5 ± 10.0 years. Of the 125 treated, 115 (92%) had past/current history of injecting drug use, 88 (70%) were receiving opioid agonist treatment and 50 (40%) were homeless. Twenty-six per cent received interferon-based and 74% DAA-only regimens. SVR (ITT) was 87% (90% with DAAs). Service uptake/HCV treatment completion rates were >95%, HCV reinfection being 2.63/100 person years (95% CI 0.67-10.33). HRQoL improved significantly at end of treatment (EOT) in those with SVR: SFLDQoL (symptoms, memory, distress, loneliness, hopelessness, sleep and stigma) (P

Radiosurgery as primary management for acromegaly.

OBJECTIVE: Transsphenoidal surgery (TSS) remains the recommended primary treatment for acromegaly. Long-term outcome data are not available for patients treated with gamma knife radiosurgery (STRS) as a primary treatment. DESIGN: Retrospective cohort study. DATA COLLECTION: notes review, laboratory results, general physician notes, patient questionnaire and death certification. PATIENTS: Twenty acromegaly patients underwent primary STRS at the National Centre for Radiosurgery, Sheffield, UK, between 1985 and 2015. MEASUREMENTS: Biochemical control (GH/IGF1), hypopituitarism, morbidity and mortality were all recorded. RESULTS: At 20 years of follow-up, control was seen in all on acromegaly-specific medication (n = 12) and 75% of those off medication (3/4). Time for 50% to achieve control on medication was 3 years, and 7.4 years off medication. Median marginal radiation dose was 27.5 Gy, and median follow-up was 166.5 months. 53% of patients developed new hypopituitarism at a median follow-up of 146 months, and the development of first onset of hypopituitarism occurred as late as 20 years after treatment. With MRI planning, no other complications were noted. Three patients underwent subsequent TSS due to poor biochemical control. During follow-up, 7 patients died at a median age of 65 years. There were no STRS-related deaths. CONCLUSION: This is the longest follow-up of patients who have undergone primary STRS for acromegaly. It shows low morbidity, but significant latency to biochemical control and new-onset hypopituitarism. This mandates very long-term follow-up for these patients. STRS has shown good long-term efficacy providing initial control can be afforded by optimal medical management. While TSS remains best practice, STRS offers an alternative for those in whom surgery is not an option.

Renal Outcomes in Children with Operated Spina Bifida in Uganda.

BACKGROUND: To describe the extent of renal disease in Ugandan children surviving at least ten years after spina bifida repair and to investigate risk factors for renal deterioration in this cohort. PATIENTS AND METHODS: Children who had undergone spina bifida repair at CURE Children's Hospital of Uganda between 2000 and 2004 were invited to attend interview, physical examination, renal tract ultrasound, and a blood test (creatinine). Medical records were retrospectively reviewed. The following were considered evidence of renal damage: elevated creatinine, hypertension, and ultrasound findings of hydronephrosis, scarring, and discrepancy in renal size >1cm. Female sex, previous UTI, neurological level, mobility, detrusor leak point pressure, and adherence with clean intermittent catheterisation (CIC) were investigated for association with evidence of renal damage. RESULTS: 65 of 68 children aged 10-14 completed the assessment. The majority (83%) reported incontinence. 17 children (26%) were performing CIC. One child had elevated creatinine. 25 children (38%) were hypertensive. There was a high prevalence of ultrasound abnormalities: hydronephrosis in 10 children (15%), scarring in 42 (64%), and >1cm size discrepancy in 28 (43%). No children with lesions at S1 or below had hydronephrosis (p = 0.025), but this group had comparable prevalence of renal size discrepancy, scarring, and hypertension to those children with higher lesions. CONCLUSIONS: Incontinence, ultrasound abnormalities, and hypertension are highly prevalent in a cohort of Ugandan children with spina bifida, including those with low neurological lesions. These findings support the early and universal initiation of CIC with anticholinergic therapy in a low-income setting.

The Initiation Factors eIF2, eIF2A, eIF2D, eIF4A, and eIF4G Are Not Involved in Translation Driven by Hepatitis C Virus IRES in Human Cells.

Animal viruses have evolved a variety of strategies to ensure the efficient translation of their mRNAs. One such strategy is the use of internal ribosome entry site (IRES) elements, which circumvent the requirement for some eukaryotic initiation factors (eIFs). Much effort has been directed to unravel the precise mechanism of translation initiation by hepatitis C virus (HCV) mRNA. In the present study, we examined the involvement of several eIFs in HCV IRES-driven translation in human cells in a comparative analysis with mRNAs bearing the encephalomyocarditis virus or the Cricket paralysis virus IRES element. Consistent with previous findings, several inhibitors of eIF2 activity, including sodium arsenite, thapsigargin, tunicamycin, and salubrinal, had no inhibitory effect on the translation of an mRNA bearing the HCV IRES, and all induced the phosphorylation of eIF2α. In addition, hippuristanol and pateamine A, two known inhibitors of eIF4A, failed to block HCV IRES-directed translation. To test the release of nuclear proteins to the cytoplasm and to analyze the formation of stress granules, the location of the nuclear protein TIA1 was tested by immunocytochemistry. Both arsenite and pateamine A could efficiently induce the formation of stress granules containing TIA1 and eIF4G, whereas eIF3 and eIF2 failed to localize to these cytoplasmic bodies. The finding of eIF4A and eIF4G in stress granules suggests that they do not participate in mRNA translation. Human HAP1 cells depleted for eIF2A, eIF2D, or both factors, were able to synthesize luciferase from an mRNA bearing the HCV IRES even when eIF2α was phosphorylated. Overall, these results demonstrate that neither eIF2A nor eIF2D does not participate in the translation directed by HCV IRES. We conclude that eIF2, eIF4A, eIF2A, and eIF2D do not participate in the initiation of translation of HCV mRNA.

Developing a community HCV service: project ITTREAT (integrated community-based test - stage - TREAT) service for people who inject drugs.

Background and aims Majority of the individuals with hepatitis C virus (HCV) infection in England are people who inject drugs, a vulnerable and disenfranchised cohort with poor engagement with secondary care. Our aim is to describe our experiences in setting up a successful nurse led HCV service at a substance misuse service (SMS). METHODS: We justify the need for a community HCV service and review the different community based models. Our experiences in engaging with stakeholders, obtaining funding, service set up, challenges faced and key recommendations are discussed. Finally, a summary of interim clinical outcomes is presented. RESULTS: A successful community based "one-stop" nurse led HCV service was set up in Dec 2013 at a large SMS. It provides all aspects of care (blood borne virus screening, non-invasive assessment of hepatic fibrosis, Hepatology input, HCV treatment, peer mentor, social and psychiatrist support, and opiod substitution) at one site. Interim clinical data indicate high service uptake with HCV treatment outcomes comparable to secondary care. CONCLUSIONS: The advent of direct acting antivirals provides a unique opportunity for HCV elimination in England by 2030. Our "one-stop" integrated and multidisciplinary community HCV model suggests that HCV care can be successfully delivered outside of a hospital setting and warrants national adoption.

Hyperprolactinaemia in first episode psychosis - A longitudinal assessment.

Little is known about hyperprolactinaemia (HPL) in first episode psychosis (FEP) patients. We investigated longitudinal changes in serum prolactin in FEP, and the relationship between HPL, and antipsychotic medication and stress. Serum prolactin was recorded in FEP patients at recruitment and again, 3 and 12months later. HPL was defined as a serum prolactin level >410mIU/L (~19.3ng/ml) for males, and a serum prolactin level >510mIU/L (~24.1ng/ml) for females. From a total of 174 people with serum prolactin measurements at study recruitment, 43% (n=74) had HPL, whilst 27% (n=21/78) and 27% (n=26/95) had HPL at 3 and 12months respectively. We observed higher serum prolactin levels in females versus males (p<0.001), and in antipsychotic treated (n=68) versus antipsychotic naïve patients (p<0.0001). Prolactin levels were consistently raised in FEP patients taking risperidone, amisulpride and FGAs compared to other antipsychotics. No significant relationship was observed between perceived stress scores (ß=7.13, t=0.21, df=11, p=0.0.84 95% CI -72.91-87.16), or objective life stressors (ß=-21.74, t=-0.31, df=8, p=0.77 95% CI -218.57-175.09) and serum prolactin. Our study found elevated rates of HPL over the course of the first 12months of illness. We found no evidence to support the notion that stress is related to elevated serum prolactin at the onset of psychosis.

Quality of life among children with spina bifida in Uganda.

BACKGROUND: Children surviving after spina bifida repair often have significant disability, the consequences of which may be more profound in low-income countries. The aim of this cross-sectional study was to measure quality of life (QOL) reported by children with spina bifida in Uganda, and to define factors associated with QOL. METHODS: QOL was measured using both the Health Utilities Index (HUI3) Tool and a visual analogue scale (VAS) marked from 0 to 10. In keeping with the WHO definition of QOL, further analysis was conducted using subjective QOL scores (using the VAS). Multivariate regression was used to investigate the association between VAS scores and prespecified variables: age, sex, hydrocephalus, mobility, urinary continence, school attendance and family size. RESULTS: Sixty two of 68 surviving children aged 10-14 were able to complete all aspects of the assessment. There was poor correlation between the VAS and HUI3 Tool (Pearson correlation 0.488). On multivariate regression, the following variables were associated with a significant change in the 10-point VAS (change in score; 95% CI): male sex (-1.45; -2.436 to -0.465), urinary continence (1.681; 0.190 to 3.172), large family size (-1.775; -2.773 to -0.777) and hydrocephalus (-1.382; -2.374 to -0.465). CONCLUSIONS: Urinary continence and family size are potentially modifiable, the former by simple and inexpensive medical management. Enhanced investment in community-based rehabilitation and support is urgently needed. Delivery of family planning services is a national priority in Uganda, and should be discussed with families as part of holistic care.

Single Electrode Deep Brain Stimulation with Dual Targeting at Dual Frequency for the Treatment of Chronic Pain: A Case Series and Review of the Literature.

Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar parafascicular complex (CMPf) modulates medial pain pathways and CMPf DBS may address the affective aspects of pain perception. Stimulation of multiple deep brain targets may offer a strategy to optimize management of patients with complex pain symptomatology. However, previous attempts to stimulate multiple targets requires multiple trajectories and considerable expense. Using a single electrode to stimulate multiple targets would help overcome these challenges. A pre-requisite of such a technique is the ability to use different stimulation parameters at different contacts simultaneously on the same electrode. We describe a novel technique in 3 patients with chronic pain syndromes for whom conventional medical and/or neuromodulation therapy had failed using a single electrode technique to stimulate PVG/PAG and CMPf at dual frequencies.

Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans.

Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [11C]DPN and [15O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [11C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [11C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit.

Using Intraoperative Ultrasonography for Spinal Cord Tumor Surgery.

BACKGROUND: Our aim was to evaluate the usefulness of modern intraoperative ultrasonography (iUS) in the resection of a wide variety of spinal intradural pathologic entities. METHODS: We evaluated patients with spinal cord disease treated between January 2006 and September 2015. Intraoperative standard B-mode images were acquired using a 3.5-MHz to 12-MHz ultrasonographic probes (linear and curvilinear) on various ultrasound machines. The benefits and disadvantages of iUS were assessed for each case. RESULTS: A total number of 158 intradural spinal lesions were operated on using iUS. Of these, 107 lesions (68%) were intradural extramedullary and 51 (32%) were intramedullary. All lesions were clearly visible using the ultrasound probe. The high-frequency linear probes (10-12 MHz) provided a better image quality compared with lower-frequency probes. Color and power-angiography modes were helpful in assessing the vascularization of the tumors and location of the major vessels in the vascular lesions. DISCUSSION: We document how iUS was used to facilitate safe and efficient spinal tumor resection at each stage of the operation. iUS was beneficial in confirmation of tumor location and extension, planning myelotomy, and estimation of degree of resection of the intramedullary tumors. It was particularly helpful in guiding the approach in redo surgeries for recurrent spinal cord tumors. CONCLUSIONS: iUS has a fast learning curve and offers additional intraoperative information that can help improve surgical accuracy and therefore may reduce procedure-related morbidity.

Ten-year survival of Ugandan infants after myelomeningocele closure.

OBJECTIVE Myelomeningocele (MM) is a neural tube defect complicated by neurological deficits below the level of the spinal lesion and, in many cases, hydrocephalus. Long-term survival of infants treated for MM in a low- and middle-income country has never been reported. This retrospective cohort study reports 10-year outcomes and factors affecting survival for infants undergoing MM repair at CURE Children's Hospital of Uganda. METHODS Patients were traced by telephone or home visit. Survival was estimated using the Kaplan-Meier method. Multivariate survival was analyzed using the Cox proportional hazards model, investigating the following variables: sex, age at surgery, weight-for-age at surgery, motor level, and presence and management of hydrocephalus. RESULTS A total of 145 children underwent MM repair between 2000 and 2004; complete data were available for 133 patients. The probability of 10-year survival was 55%, with 78% of deaths occurring in the first 5 years. Most of the deaths were not directly related to MM; infection and neglect were most commonly described. Lesions at motor level L-2 or above were associated with increased mortality (HR 3.176, 95% CI 1.557-6.476). Compared with repair within 48 hours of birth, surgery at 15-29 days was associated with increased mortality (HR 9.091, 95% CI 1.169-70.698). CONCLUSIONS Infants in low- and middle-income countries with MM can have long-term survival with basic surgical intervention. Motor level and age at surgery were significant factors influencing outcome. Education of local health care workers and families to ensure both urgent referral for initial treatment and subsequent access to basic medical care are essential to survival.