Severe Sepsis Associated With Multiorgan Failure and Precipitating Nonhepatic Hyperammonemia Crisis in Late-Onset Ornithine Transcarbamylase Deficiency: A Case Report and Literature Review.

Sepsis is characterized by a dysregulated immune response to an infection. It is a major public health problem owing to its high mortality and morbidity. Sepsis is a medical emergency and requires aggressive and timely management. It can cause multiorgan failure, unmask an existing but undiagnosed disease such as ornithine transcarbamylase deficiency (OTCD), or make a known well-controlled disease worse. We present the case of a 52-year-old male who was brought to the emergency department unresponsive. He was diagnosed with severe sepsis which was associated with multiorgan failure and hyperammonemia crisis. Hyperammonemia was due to a newly diagnosed, late-onset OTCD which was unmasked by severe sepsis. This case will enable physicians to be aware and consider OTCD in a patient presenting with severe sepsis, altered mentation, and seizures, with no obvious cause of hyperammonemia.

Syncope Secondary to Concomitant Ingestion of Tizanidine and Alcohol in a Patient With Alcohol Use Disorder.

Syncope is the transient loss of consciousness due to cerebral hypoperfusion. A significant number of individuals experience a syncopal attack at one stage of their lives. The common causes of syncope include vasovagal syncope, orthostatic hypotension, and cardiac causes. Drugs are also associated with causing syncope. The drugs involved are mostly those that depress the central nervous system, and concomitant use of more than one of such drugs increases the risk of syncope even further. Tizanidine and alcohol individually can cause hypotension and combining both drugs is not advised due to heightened central nervous system depression and profound hypotension. We present a case of a 53-year-old female with alcohol use disorder who presented with a first-time syncopal attack due to postural hypotension after ingesting both tizanidine and alcohol concurrently. Co-administration of tizanidine and alcohol is not advised, however, cases of syncope have been rarely reported with concomitant use. This case will enlighten physicians to counsel patients about the need to abstain from alcohol consumption when taking tizanidine.

Bilateral Empyema With Beta Hemolytic Group C Streptococcus and Streptococcus constellatus Co-infection Resulting From an Esophageal Perforation and Associated With Septic Shock, Diffuse ST Elevation, and New-Onset Atrial Fibrillation.

Empyema is the collection of pus in the pleural cavity and most times, it occurs unilaterally. It is often associated with underlying pneumonia, but other causes have been identified as well. When it occurs after an esophageal perforation, which in itself is also rare, morbidity and mortality are even higher. Esophageal perforation can cause life-threatening complications due to its close proximity to the vital organs of the mediastinum, necessitating its timely diagnosis and aggressive management. Bacteria forming part of the normal esophageal and oral flora are the most common causative pathogens for empyema from an esophageal perforation. Streptococcus constellatus and group C Streptococci, though both rare and often not taken seriously, have been identified as individual causes of empyema. We present a case of a 58-year-old male who presented with a worsening cough, chest pain, and shortness of breath after choking on a fish bone. He was diagnosed with bilateral loculated empyema resulting from esophageal perforation with the pleural fluid culture isolating both group C streptococcus and Streptococcus constellatus. He also developed respiratory failure, mediastinitis, and septic shock. This case will enable physicians to take empyema caused by these bacteria seriously and also to include esophageal perforation as a differential diagnosis when a patient presents with bilateral empyema associated with chest pain and electrocardiographic changes.

An Atypical Presentation of Burkitt Lymphoma Presenting As Large Intra-abdominal Masses Compressing Multiple Organs With Peri-Pericardial Involvement in an HIV Patient: A Case Report and Literature Review.

Many types of malignancies have been associated with immunodeficiency states, especially patients who are HIV positive. Burkitt lymphoma (BL) is one of those malignancies associated with HIV and it presents in three varieties. The endemic form is primarily seen in children, and it is associated with the Epstein-Barr virus (EBV). In this form, patients with Burkitt's present with a large jaw mass. The second variety is seen in older adults. These patients usually present with abdominal and pelvic masses. This subtype is more prominent in the United States. The third variety of BL is seen in patients who are HIV positive. In this case report, we present an atypical presentation of BL secondary to undiagnosed HIV/AIDS with a very large tumor burden causing compressive symptoms. This case will further guide healthcare professionals in diagnosing BL, which presents uniquely in high-risk populations. This report will also serve as a review of the diagnosis and treatment options of BL.

Development of novel pyrimidine nucleoside analogs as potential anticancer agents: Synthesis, characterization, and In-vitro evaluation against pancreatic cancer.

The present study proposed modification of 5-FU by conjugation with an acyl chloride and a 5-membered heterocyclic ring to improve its in-vitro cytotoxicity and metabolic stability. XYZ-I-71 and XYZ-I-73 were synthesized by introducing a tetrahydrofuran ring on 5-fluorocytosine (a precursor of 5-FU) and conjugation with octanoyl chloride and lauroyl chloride, respectively. The structure of the synthesized compounds was validated using NMR and micro-elemental analysis. The antiproliferative activity of the analogs was determined against MiaPaCa-2, PANC-1, and BxPC-3 pancreatic cancer cells. The analog's stability in human liver microsomes was quantified by HPLC. We found that the XYZ-I-73 (IC50 3.6 ± 0.4 µM) analog was most effective against MiaPaCa-2 cells compared to XYZ-I-71(IC50 12.3 ± 1.7 µM), GemHCl (IC50 24.2 ± 1.3 µM), Irinotecan (IC50 10.1 ± 1.5 µM) and 5-FU (IC50 13.2 ± 1.1 µM). The antiproliferative effects of this analog in Miapaca-2 cells is evident based on it having a 7-fold,3-fold, and 4-fold increased cytotoxic effect over Gem-HCl, Irinotecan, and 5-FU, respectively. On the other hand, XYZ-I-71 exhibited a 2-fold increased cytotoxic effect over Gem-HCl but a comparable cytotoxic effect to 5-FU and Irinotecan in MiaPaCa-2 cells. A similar trend of higher XYZ-I-73 inhibition was observed in PANC-1 and BxPC-3 cultures. For 48-h MiaPaCa-2 cell migration studies, XYZ-I-73 (5 µM) significantly reduced migration (# of migrated cells, 168 ± 2.9), followed by XYZ-I-71(315±2.1), Gem-HCl (762±3.1) and 5-FU (710 ± 3.2). PARP absorbance studies demonstrated significant inhibition of PARP expression of XYZ-I-73 treated cells compared to 5-FU, GemHCl, and XYZ-I-71. Further, BAX and p53 expressions were significantly increased in cells treated with XYZ-I-73 compared to 5-FU, GemHCl, and XYZ-I-71. In-vitro, metabolic stability studies showed that 80 ± 5.9% of XYZ-I-71 and XYZ-I-73 remained intact after 2 h exposure in liver microsomal solution compared to 5-FU. The XYZ-I-73 analog demonstrated a remarkable cytotoxic effect and improved in-vitro metabolic stability over the selected standard drugs and may have potential anticancer activity against pancreatic cancer.

An Atypical Case of Polycystic Ovarian Syndrome and Possible Newly Diagnosed Systemic Lupus Erythematosus Complicated With a Cerebrovascular Accident in a Young Female: A Case Report.

Polycystic ovary syndrome (PCOS) is the leading cause of endocrine disorders among females of reproductive age and is linked with autoimmune disorders. PCOS has been associated with autoantibodies such as antinuclear antibody (ANA), anti-thyroid, and anti-Smith (anti-SM). Young patients with PCOS and systemic lupus erythematosus (SLE) have up to a 10-fold increase in stroke. We present a case of a patient with a history of PCOS (on metformin), hypothyroidism, and pulmonary embolism who presented to the emergency room with acute left-sided weakness. She was extensively investigated for risk factors and was eventually diagnosed with a cerebrovascular accident secondary to possible SLE with positive ANA (1:160, nuclear homogenous pattern). The diagnosis of PCOS, coupled with autoantibodies and recurring episodes of thromboembolic events, rendered her case management complex. She received tenecteplase and had thrombectomy done twice because of recurrent thrombotic events during her hospital stay. She passed away on the fifth day post-thrombectomy from a possible massive pulmonary embolism with hemodynamic compromise. There is a need for more research to comprehend the underlying mechanisms of SLE and PCOS to guide the proper management of patients in this situation.

Biological evaluation of novel gemcitabine analog in patient-derived xenograft models of pancreatic cancer.

Gemcitabine (Gem) has been a standard first-line drug for pancreatic cancer (PCa) treatment; however, Gem's rapid metabolism and systemic instability (short half-life) limit its clinical outcome. The objective of this study was to modify Gem into a more stable form called 4-(N)-stearoyl-gemcitabine (4NSG) and evaluate its therapeutic efficacy in patient-derived xenograft (PDX) models from PCa of Black and White patients.Methods 4NSG was synthesized and characterized using nuclear magnetic resonance (NMR), elemental analysis, and high-performance liquid chromatography (HPLC). 4NSG-loaded solid lipid nanoparticles (4NSG-SLN) were developed using the cold homogenization technique and characterized. Patient-derived pancreatic cancer cell lines labeled Black (PPCL-192, PPCL-135) and White (PPCL-46, PPCL-68) were used to assess the in vitro anticancer activity of 4NSG-SLN. Pharmacokinetics (PK) and tumor efficacy studies were conducted using PDX mouse models bearing tumors from Black and White PCa patients.Results 4NSG was significantly stable in liver microsomal solution. The effective mean particle size (hydrodynamic diameter) of 4NSG-SLN was 82 ± 6.7 nm, and the half maximal inhibitory concentration (IC50) values of 4NSG-SLN treated PPCL-192 cells (9 ± 1.1 µM); PPCL-135 (11 ± 1.3 µM); PPCL-46 (12 ± 2.1) and PPCL-68 equaled to 22 ± 2.6 were found to be significantly lower compared to Gem treated PPCL-192 (57 ± 1.5 µM); PPCL-135 (56 ± 1.5 µM); PPCL-46 (56 ± 1.8 µM) and PPCL-68 (57 ± 2.4 µM) cells. The area under the curve (AUC), half-life, and pharmacokinetic clearance parameters for 4NSG-SLN were 3-fourfold higher than that of GemHCl. For in-vivo studies, 4NSG-SLN exhibited a two-fold decrease in tumor growth compared with GemHCl in PDX mice bearing Black and White PCa tumors.Conclusion 4NSG-SLN significantly improved the Gem's pharmacokinetic profile, enhanced Gem's systemic stability increased its antitumor efficacy in PCa PDX mice bearing Black and White patient tumors.

Evaluation of Anticancer Activity of Zhubech, a New 5-FU Analog Liposomal Formulation, against Pancreatic Cancer.

Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancers have been masked by high drug toxicities, adverse reactions, and resistance. The use of nanocarriers such as liposomes to overcome these unwanted effects has become very popular. This study aims to formulate 1,3-bistertrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and to evaluate itsstability, release kinetics, in vitro and in vivo anticancer activities, and biodistribution in different tissues. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticles (Rho-LnPs) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP), as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnPs in vivo using inductively coupled plasma mass spectrometry (ICP-MS). The mean hydrodynamic diameters of blank LnPs and Zhubech were 90.0 ± 0.65 nm and 124.9 ± 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4 °C and 25 °C for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R2 value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroid (IC50Zhubech = 3.4 ± 1.0 µM vs. IC50MFU = 6.8 ± 1.1 µM) and organoid (IC50Zhubech = 9.8 ± 1.4 µM vs. IC50MFU = 42.3 ± 1.0 µM) culture models. Confocal imaging confirmed a high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor-efficacy studies in a PDX bearing mouse model revealed a more than 9-fold decrease in mean tumor volumes in Zhubech-treated (108 ± 13.5 mm3) compared to 5-FU-treated (1107 ± 116.2 mm3) animals, respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.

Synthesis, characterization, and anticancer evaluation of 1,3-bistetrahydrofuran-2yl-5-FU as a potential agent for pancreatic cancer.

The failure of current chemotherapeutic agents for pancreatic cancer (PCa) makes it the most aggressive soft tissue tumor with a 5-year survival of slightly above 10% and is estimated to be the second leading cause of cancer death by 2030. OBJECTIVE: The main aim was to synthesize, characterize and evaluate the anticancer activity of 1,3-bistetrahydrofuran-2yl-5FU (MFU). METHODS: MFU was synthesized by using 5-fluorouracil (5-FU) and tetrahydrofuran acetate, and characterized by nuclear magnetic resonance (NMR), micro-elemental analysis, high-performance liquid chromatography (HPLC), and liquid chromatography with mass spectrophotometry (LC-MS). MFU and Gemcitabine hydrochloride (GemHCl) were tested for antiproliferative activity against MiaPaca-2 and Panc-1 cell lines. RESULTS: The half-minimum inhibitory concentration (IC50) of MFU was twice lower than that of GemHCl when used in both cell lines. MiaPaca-2 cells (MFU-IC50 = 4.5 ± 1.2 µM vs. GemHCl-IC50 = 10.3 ± 1.1 µM); meanwhile similar trend was observed in Panc-1 cells (MFU-IC50 = 3.0 ± 1 µM vs. GemHCl-IC50 = 6.1 ± 1.03 µM). The MFU and GemHCl effects on 3D spheroids showed a similar trend (IC50-GemHCl = 14.3 ± 1.1 µM vs. IC50-MFU = 7.2 ± 1.1 µM) for MiaPaca-2 cells, and (IC50-GemHCl = 16.3 ± 1.1 µM vs. IC50-MFU = 9.2 ± 1.1 µM) for Panc-1 cells. MFU significantly inhibited clonogenic cell growth, and induced cell death via apoptosis. Cell cycle data showed mean PI for GemHCl (48.5-55.7) twice higher than MFU (24.7 to 27.9) for MiaPaca-2 cells, and similarly to Panc-1 cells. The in-vivo model showed intensely stained EGFR (stained brown) in all control, GemHCl and MFU-treated mice bearing subcutaneous PDX tumors, however, HER2 expression was less stained in MFU-treated tumors compared to GemHCl-treated tumors and controls. Mean tumor volume of MFU-treated mice (361 ± 33.5 mm3) was three-fold lower than GemHCl-treated mice (1074 ± 181.2 mm3) bearing pancreatic PDX tumors. CONCLUSION: MFU was synthesized with high purity and may have potential anticancer activity against PCa.

Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain.

Drug delivery into the brain has for long been a huge challenge as the blood-brain barrier (BBB) offers great resistance to entry of foreign substances (with drugs inclusive) into the brain. This barrier in healthy individuals is protective to the brain, disallowing noxious substances present in the blood to get to the brain while allowing for the exchange of small molecules into the brain by diffusion. However, BBB is disrupted under certain disease conditions, such as cerebrovascular diseases including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and cancers. This review aims to provide a broad overview of present-day strategies for brain drug delivery, emphasizing novel delivery systems. Hopefully, this review would inspire scientists and researchers in the field of drug delivery across BBB to uncover new techniques and strategies to optimize drug delivery to the brain. Considering the anatomy, physiology, and pathophysiological functioning of the BBB in health and disease conditions, this review is focused on the controversies drawn from conclusions of recently published studies on issues such as the penetrability of nanoparticles into the brain, and whether active targeted drug delivery into the brain could be achieved with the use of nanoparticles. We also extended the review to cover novel non-nanoparticle strategies such as using viral and peptide vectors and other non-invasive techniques to enhance brain uptake of drugs.

Factors associated with measles resurgence in the United States in the post-elimination era.

There have been growing concerns of a potential re-establishment of measles transmission in the United States (US) in the years to come. This study aims to explore potential factors underlying the resurgence of measles in the US by objectively assessing the associations between annual incidence rates (AIR), case importation, vaccination status and disease outbreaks. Data on measles transmission between January 1st, 2001 and December 31st, 2019 were obtained from the national centres for disease control and prevention (CDC) surveillance databases and other published reports. Changes in incidence rates over time were assessed by binomial regression models. Of the 3874 cases of measles in the US over the study period, 3506 (90.5%, 95% CI: 89.5-91.4) occurred in US residents. The AIR per million population in US residents over this period was 0.60 (95% CI: 0.59-0.61), with an overall significant increase over time (p = 0.011). The median percentage of imported and vaccinated cases were 36% [17.9-46.6] and 15% [12.1-23.2] respectively. There was a significant decrease in the percentage of imported cases (p < 0.001) but not of vaccinated cases (p = 0.159) over time. There was a moderate and weak negative correlation between the AIR and the percentage of imported and vaccinated cases respectively (r = -0.59 and r = -0.27 respectively). On multiple linear regression there was a significant linear association between the AIR and the number of outbreaks (p = 0.003) but not with the percentage of imported cases (p = 0.436) and vaccinated cases (p = 0.692), R2 = 0.73. Strong negative and positive correlations were seen between the number of outbreaks and the percentage of imported cases (r = -0.61) and the of number states affected (r = 0.88) respectively. Despite the overall reduction in the percentage of imported cases of measles over the past two decades, pockets of internal transmission of the disease following importation via increasing number of outbreaks in unvaccinated subpopulations, reinforced by vaccine hesitancy, account for the sustained increase in measles incidence rates in the US. Controlling indigenous transmission through efficient vaccination coverage in at-risk subpopulations and among international US travellers, improved disease surveillance and rapid outbreak containment are essential in curbing the measles resurgence.

Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models.

Gemcitabine (Gem), a nucleoside analog, is a preferred choice of treatment for pancreatic cancer (PCa) and often used in combination therapy against wide range of solid tumors. It is known to be rapidly inactivated in blood by cytidine deaminase. The objective of the study was to improve the systemic stability and anticancer activity of modified Gem termed 4-N-stearoylGem (4NSG) In this study, the IC50 values of 4NSG treated MiaPaCa-2 and primary pancreatic cancer (PPCL-46) cultures were significantly lower when compared with gemcitabine hydrochloride (GemHCl) treated cultures. In acute toxicity study, liver enzyme level of aspartate aminotransferase (AST) of the control mice was not significantly different from AST levels of 4NSG and GemHCl treated mice. However, alanine aminotransferase (ALT) level of control mice (67 ± 5 mUnits/mL) was significantly lower compared with ALT levels of GemHCl (232 ± 28 mUnits/mL) and that of 4NSG (172 ± 22 mUnits/mL) (p < 0.0001). More importantly, ALT level of 4NSG was lower than ALT level of GemHCl (p < 0.05). Although ALT levels were elevated, pathological images of liver and kidney tissues of control, GemHCl and 4NSG treated mice revealed no architectural changes and no significant change in mice weight was observed during treatment. The bioavailability (AUC) of 4NSG was 3-fold high and significantly inhibited the tumor growth as compared with equivalent dose of GemHCl. Immunohistochemical staining revealed that 4NSG significantly inhibited the expression vascular endothelial growth factor (VEGF) receptor. The study is unique because it established, for the first time, enhanced anticancer activity of 4NSG against pancreatic patient-derived xenograft (PDX) mouse model and PPCL-46 cells compared with Gem. 4SGN enhanced pharmacokinetic profile and improved the therapeutic efficacy of the standard-of-care Gem. Lastly, 4GSN showed a remarkable tumor growth inhibition and revealed significant antiangiogenic activity in 4GSN treated pancreatic PDX tumor.

Evolutionary aspects of non-metastatic breast cancer after primary treatment in a sub-Saharan African setting: a 16-year retrospective review at the Douala general hospital, Cameroon.

BACKGROUND: Breast cancer has a high case fatality rate in sub-Saharan Africa, and this is chiefly because of late detection and inadequate treatment resources. Progressive renovations in diagnostic and management modalities of non-metastatic breast cancer (NMBC) have been noted in the region but there is paucity of data describing the clinical progress of patients with NMBC. This study sought to determine the rates of local relapse, distant metastasis and sequelae and the time span from initial treatment to the occurrence of these adverse events among patients with NMBC. METHODS: This was a retrospective review of medical records of patients with histologically confirmed NMBC at the department of radiation therapy and oncology of the Douala General Hospital in Cameroon from the January 1997 to December 2012 period. Clinicopathological and treatment characteristics as well as occurrences of adverse events were studied. RESULTS: A total of 260 cases were reviewed of which 224/260 (86.2%) had invasive ductal carcinoma. Surgery was performed on 258/260 cases (99.2%) with 187/258 (72.5%) being modified radical mastectomies. Various treatment combinations were used in up to 228/260 patients (87.5%) while surgery alone was the treatment in the remaining 32 cases (12.5%). Metastasis occurred in 142/260 cases (54.6%) of which 68/142 (26.2%) were local relapses and 74/142 (28.5%) were distant metastases. Among the cases of distant metastasis, 9.2% were bone, 8.5% lungs, 6.9% nodal, and 5.4% brain. Metastasis to multiple organs was noted in 4.7% of these cases. The median periods of occurrence of local relapse and distant metastases were 13 and 12 months respectively. Sequelae occurred in 26/260 cases (10%) and were noted after an average of 30 months. The main sequelae were lymphoedema (6.5%) and lung fibrosis (1.5%). At the end of the period under review, 118/260 patients (45.4%) were alive and disease-free with a median follow up time of 24 months. CONCLUSIONS: Adverse events were frequent among patients who received primary treatment for NMBC. Available cancer therapeutic modalities ought to be supplemented with efficient strategies of follow-up and monitoring so as to optimize the care provided to these patients and improve on their survival.

Spina bifida cystica and severe congenital bilateral talipes equinovarus in one twin of a monoamniotic pair: a case report.

BACKGROUND: Spina bifida and congenital talipes equinovarus (CTEV) are common congenital malformations which may occur together and increase morbidity. Monozygous twins are particularly at risk of these malformations and discordance in one type of malformation is typical. The occurrence of both spina bifida and CTEV in one twin of a monozygotic pair is rare. CASE PRESENTATION: A 22 year-old Cameroonian primigravida at 36 weeks of a twin gestation was received in our district hospital at the expulsive phase of labour on a background of sub-optimal antenatal care. A caesarean section indicated for cephalo-pelvic disproportion was performed and life monoamniotic male twins were extracted. The first twin was normal. The second twin had spina bifida cystica and severe bilateral CTEV. Routine postnatal care was ensured and at day 2 of life, the affected twin was evacuated to a tertiary hospital for proper management. He was later on reported dead from complications of hydrocephalus. CONCLUSIONS: Spina bifida cystica with severe bilateral CTEV in one twin of a monoamniotic pair illustrates the complexity in the interplay of causal factors of these malformations even among monozygotic twins who are assumed to share similar genetic and environmental features. The occurrence and poor outcome of the malformations was probably potentiated by poor antenatal care. With postnatal diagnoses, a better outcome was difficult to secure even with prompt referral. Early prenatal diagnoses and appropriate counseling of parents are cardinal.

Motives for change of first-line antiretroviral therapy regimens in an unselected cohort of HIV/AIDS patients at a major referral centre in South-west Cameroon.

OBJECTIVE: The rapid scale-up of antiretroviral therapy (ART) coverage in sub-Saharan Africa has encountered the challenge of maintaining international clinical standards of ART utilization and change of ART regimens. In Cameroon, scarce reports have documented the motives for change of ART. This study had as objective to investigate the reasons for switch in ART through a secondary analysis and descriptive synthesis of data from a cross-sectional study at the Limbe Regional Hospital. RESULTS: One hundred participants were included. Their mean age was 40.2 ± 8.0 years and 70% of them were females. The median duration of ART use was 60 months. Zidovudine-Lamivudine-Nevirapine regimen was received by 83% of patients while the Stavudine-Lamivudine-Nevirapine regimen had the highest median duration of use (58 months). Most patients had experienced changes in ART (especially from Stavudine-Lamivudine-Nevirapine regimen) with the chief reason being unavailability of their previous regimens. Four patients had their ART changed due to active tuberculosis, 4 due to pregnancy and 7 due to ART toxicity (4 and 3 for peripheral neuropathy and lipodystrophy respectively). In conclusion, shortages in ART hugely influenced switch in regimens. In such a context, modifications in ART possibly deviate from guidelines with resultant sub-optimal therapy and enhanced drug resistance.

Diagnostic and therapeutic challenges of an ambiguous cystic kidney disease in a resource limited setting: a case report.

BACKGROUND: Unilateral renal cystic disease is a rare condition that shares morphological similarities with multicystic dysplastic kidney, the former often distinguished from the latter on some clinical and histopathological grounds. However serious diagnostic and therapeutic dilemmas set in when there is a considerable overlap in the distinguishing features between these entities. CASE PRESENTATION: A 19-year-old African female presented with a chronic severe debilitating right lower quadrant abdominal pain refractory to analgesics. Biochemical investigations and imaging studies revealed a non-functional polycystic right kidney and no identifiable pelvicalyceal system or ureter but with preserved renal function. The marked overlap in clinical presentation between unilateral renal cystic disease and multicystic dysplastic kidney in this patient necessitated further investigation to pose an appropriate diagnosis. A right nephrectomy was performed and histopathological analysis of the resected kidney done, the results of which were more consistent with unilateral renal cystic disease. The post-operative course was favorable. CONCLUSION: Unilateral renal cystic disease with an ipsilateral non-functional kidney and an atretic pelvicalyceal system is a very rare condition that needs to be distinguished from multicystic dysplastic kidney in order to guide management and set prognosis. A suspicion of either of these diseases therefore warrants a thorough clinical evaluation and the appropriate combination of biochemical and imaging investigations.

Right iliac vein thrombosis mimicking acute appendicitis in pregnancy: a case report.

BACKGROUND: Right iliac vein thrombosis is uncommon in pregnancy. Nonetheless, when it does occur, its presentation could be very unspecific with important diagnostic challenges and this could have negative therapeutic consequences especially in a resource limited setting. CASE PRESENTATION: The historical, clinical and laboratory data of a 30 year old G2P1001 woman of African ethnicity at 11 weeks of gestation pointed towards a right iliac vein thrombosis missed for an acute appendicitis with subsequent appendectomy and failure to cure. Following the diagnosis of right iliac vein thrombosis post-appendectomy, the patient was started on low molecular weight heparin and the clinical progress thereafter was favourable. CONCLUSION: Pelvic vein thrombosis should be considered a differential diagnosis of intractable lower abdominal pain in early pregnancy. A high index of suspicion could lead to early diagnosis, prompt management and a favourable prognosis even in a low-income setting.

Concurrent hyperthyroidism and papillary thyroid cancer: a fortuitous and ambiguous case report from a resource-poor setting.

BACKGROUND: Concurrent thyroid cancer (TC) and hyperthyroidism (HT) is rare though increasingly being reported. HT due to TC is much rarer and more challenging especially in Africa where TC and HT have significant case fatality rates. CASE PRESENTATION: We present a 37-year-old Cameroonian female who had been on irregular regimens of propranolol and digoxin as treatment for worsening palpitations for 12 months. She came to our district hospital for her propranolol medication refill. We fortuitously identified features of HT and found a left uninodular goiter with no cervical lymphadenopathy. She was referred for thyroid assessment which suggested primary HT and an enlarged heterogeneous left lobe with a well-defined homogenous solid mass. We restarted her on propranolol and referred her for a course of methimazole. At the referral hospital, she also underwent a left thyroid lobectomy. The resected lobe was sent for histopathology which revealed a neoplastic nodule with features suggestive of a papillary thyroid cancer (PTC) causing HT. The patient's clinical progress postoperatively was good and there was regression of hyperthyroid symptoms. CONCLUSIONS: The historical, clinical, and laboratory findings were suggestive of HT due to PTC. A high index of suspicion, prompt referral and counter-referral lead to a positive outcome of such a rare case in a resource poor setting. We advocate for systematic and careful evaluation of all thyroid nodules.