Altered mitochondrial DNA copy number in cervical exfoliated cells among high­risk HPV­positive and HPV­negative women.

The majority of cervical cancer cases are due to human papillomavirus (HPV) infection. However, certain cases of cervical cancer are not caused by HPV. Recent studies have shown a link between altered mitochondrial DNA (mtDNA) copy number, an indicative measure of mitochondrial dysfunction, and cervical cancer in women who test positive for HPV. However, the role of the mtDNA copy number in HPV-negative cervical cancer has remained elusive. In the present study, the mtDNA copy number was determined using quantitative PCR as the ratio between mtDNA and nuclear DNA in 287 ThinPrep cervical samples, including 143 cases with cervical abnormalities and 144 control subjects with high-risk (hr)-HPV positive or HPV-negative status. In an overall analysis of cases categorized based on the cytology diagnosis into squamous cervical carcinoma/high-grade squamous intraepithelial lesions (SCC/HSIL), low-grade squamous intraepithelial lesions (LSIL) and normal controls, the mtDNA copy number was significantly higher in all cases compared to the controls and a higher mtDNA copy number was observed in SCC/HSIL compared to LSIL cases. In the stratification analyses based on hr-HPV positive and HPV-negative status, an increased mtDNA copy number was observed in the cases compared with the controls regardless of their HPV status (P<0.05). When cases with cervical abnormalities were categorized based on histological diagnosis into cervical intraepithelial neoplasia (CIN)2/CIN3 and CIN1, an overall analysis indicated an increased mtDNA copy number in CIN2/CIN3 compared to CIN1 (P=0.01). Stratification analyses of these cases based on HPV status revealed a higher mtDNA copy number in CIN2/CIN3 compared to CIN1 regardless of HPV infection (P<0.05). These results showed that an elevated mtDNA copy number in subjects with cervical abnormalities was not influenced by the HPV status and suggested the possibility of its role in the progression of cervical cancer. The increased mtDNA copy number may be an adaptive response mechanism to compensate for mtDNA oxidative stress and energy deficiency, possibly induced by HPV infection and other environmental exposures.

Early initiation of insulin attenuates histological and functional changes in the liver of streptozotocin-induced diabetic rats using 99mTc-sulfur colloid functional imaging.

This study aimed to investigate the effect of insulin on the reticuloendothelial system (RES) in the liver and spleen in diabetic rats. Sprague Dawley rats were divided into control, diabetic rats (DM) and diabetic rats treated with insulin (IDM) for 2 weeks. Rats were imaged with technetium-99m-sulfur colloid (99mTc-SC) tracer to determine regional distributions of the tracer for all groups by drawing regions of interest and then obtained the ratios as the cumulative counts of heart, liver, and spleen to the whole body (WB). Liver tissue from sacrificed rats from each group was examined by light and electron microscopy. 99mTc-SC uptake ratios showed a lower liver to WB uptake ratio in the DM rats compared to both controls and IDM rats. Electron microscopy showed severe vacuolization of the hepatocytes of DM rats. The IDM rats show complete resolution of the vacuolization. The early administration of insulin for 2 weeks to diabetic rats could significantly resolve the phagocytic RES function and histological changes in the liver.

Patterns of drug overdose deaths in Kuwait from 2014 to 2018.

Background: Kuwait is an Arabian Gulf couFntry with a population of around 4.4 million as of 2020. In recent years, government based news agencies have commonly exposed drug smuggling plots that were foiled by local authorities. We attempted to study the patterns of drug overdose deaths in Kuwait, which we believe is a good method to address the effect of illicit drug use in the country. Methodology: All cases that were signed out as drug overdose death were collected from the General department of criminal evidence. The relationship between demographic factors and drug types were analyzed using various statistical methodologies. Results: 344 victims were identified from 2014 to 2018. The majority of whom were Kuwaiti nationals (67%) and the average age of death was 38. Hawalli governorate had the highest number of cases, while Jahra governorate had the least. Morphine appeared to be the most common drug found in the victims post mortem (79.9%) followed by benzodiazepines (43%). Our study has an extremely low female number of victims (2.6%). Some substances that are commonly abused globally eg heroin and cocaine were rarely recovered in our study. The number of cases have had an increase over the study period with the highest number of cases in 2018. Conclusion: The current study is the first of its kind in Kuwait and one of the first in the middle east region. It is evident that illicit drug use and subsequent drug overdose deaths are on a rise in Kuwait and government agencies need to put a strategic plan to address and reduce this problem.

Early Versus Late Acute Antibody-Mediated Rejection Among Renal Transplant Recipients in Terms of Response to Rituximab Therapy: A Single Center Experience.

OBJECTIVES: There are no comparable trials concerning the use of rituximab among renal transplant recipients with acute antibody-mediated rejection. Here, we compared early and late acute antibody-mediated rejection in renal transplant recipients in terms of response to rituximab therapy. MATERIALS AND METHODS: Of 1230 kidney transplants performed at Hamed Al-Essa Organ Transplant Center (Kuwait) over the past 10 years, 103 recipients developed acute antibody-mediated rejections and were subcategorized into 4 groups according to the onset of rejection and rituximab treatment. All patients received the standard treatment for acute antibody-mediated rejection according to our protocol (plasma exchange and intravenous immunoglobulin). We added rituximab to the treatment regimen in 2 groups of patients: 27 patients with early rejection (group 1) and 38 patients with late rejection (group 2). Groups 3 and 4 represented nonrituximab groups, with 20 patients with early (group 3) and 18 patients with late rejection (group 4). We compared the 4 groups regarding graft and patient outcomes. RESULTS: All patients were comparable regarding patient age, sex, pretransplant type of dialysis, viral profile, type of induction, donor criteria, and pretransplant comorbidities. We observed that delayed and slow graft function were significantly higher in groups 1 and 3 (P = .016); however, we found no significant differences in the 4 groups regarding new-onset diabetes after transplant, BK viral infection, and malignancy. Graft outcomes were significantly better in groups 1 and 2 than in groups 3 and 4 (P = .028). However, patient outcomes were comparable in the 4 groups (P > .05). CONCLUSIONS: Early acute antibody-mediated rejection in renal transplant recipients had significantly better outcomes when rituximab was added to the standard treatment regimen.

Epidermal growth factor receptor mutations in nonsmall cell lung carcinoma patients in Kuwait.

CONTEXT: Nonsmall cell lung carcinoma (NSCLC) is the most frequently diagnosed form of lung cancer in Kuwait. NSCLC samples from Kuwait have never been screened for epidermal growth factor receptor (EGFR) gene aberration, which is known to affect treatment options. AIMS: This study investigated the feasibility of using fine-needle aspiration (FNA) material for mutational screening, and whether common EGFR mutations are present in NSCLC samples from Kuwait. SETTINGS AND DESIGN: Eighteen NSCLC samples from five Kuwaitis and 13 non-Kuwaitis were included in this study. MATERIALS AND METHODS: DNA was extracted from FNA cell blocks and screened for EGFR gene mutations using peptide nucleic acid (PNA)-clamp assay, and EGFR gene amplification using fluorescent in situ hybridization (EGFR-FISH). EGFR protein expression was assessed using immunohistochemistry. RESULTS: Five EGFR mutations were detected in five non-Kuwaiti NSCLC patients (27.8%). EGFR gene amplification was evident in 10 samples (55.5%) by direct amplification or under the influence of chromosomal polysomy. Four samples had EGFR mutations and EGFR gene amplification, out of which only one sample had coexisting EGFR overexpression. CONCLUSIONS: Given the evidence of EGFR gene alterations occurring in NSCLC patients in Kuwait, there is a need to incorporate EGFR gene mutational screen for NSCLC patients to implement its consequent use in patient treatment.

Nonossifying fibroma (metaphyseal fibrous defect) of the mandible in a 15-year-old boy.

We describe a rare case of nonossifying fibroma of the mandible in a 15-year-old boy who presented with a left mandibular swelling. Conventional imaging showed an expansile radiolucent lesion involving the angle and the body of the left mandible. The lesion was curetted, and a miniplate was implanted at the excision site. Microscopic examination of the removed specimen revealed a cellular lesion characterized by a proliferation of uniform spindle-shaped cells in a vague but prominent storiform pattern, which represented the classic appearance of nonossifying fibroma. Three months later, radiography detected a fracture of the implantation plate. The area was re-explored with curettage of the soft tissue, which on microscopy demonstrated findings similar to the initial curettage findings. Follow-up radiology revealed satisfactory healing of the jaw, and no further recurrence was seen 2 years after the initial surgery. We present this case to highlight the importance of recognizing nonossifying fibroma in the mandible, which can be easily confused with more common mandibular lesions.

Patterns of suicide in Kuwait: a retrospective descriptive study from 2003-2009.

BACKGROUND: Prior to the invasion of Kuwait by Iraq in 1990, suicides were almost unheard of in Kuwait. However, there has been a notable increase in the referrals of suicide cases to the forensic authorities since then. A review of suicide cases was performed to investigate the demographics of this phenomenon and the suicide modalities used and to uncover issues that can be addressed by the region's government. METHODS: The sole source of data was the general department of criminal evidence (GDCE), where cases are referred by police authorities and by hospital investigators from the entire country. All cases signed out by forensic investigators as "suicide" during the time period 2003-2009 were retrieved. A full review of the data from the case files was made. This included demographic data, scene examination, radiographic investigations, autopsies with histo-pathological examination findings and toxicological screening results in each case. RESULTS: A total of 347 cases were retrieved and studied. Hanging was found to be the most common suicide modality used by subjects (60 %). Non-citizens constituted 87 % of cases, and no significant difference was found between married and single subjects or between Muslims and non-Muslims. Regions that were more populated with an expatriate labour force had the highest suicide prevalence. CONCLUSION: The government of Kuwait needs to investigate the dire conditions in which some expatriates live and to improve their situation. More control over the dispensing of certain medications needs to be enforced. Finally, strict firearm control could help reduce the suicide rates in Kuwait.

Patterns of accidental deaths in Kuwait: a retrospective descriptive study from 2003-2009.

BACKGROUND: Accidents are a preventable cause of death. Unfortunately it accounts for a large number of deaths in many societies. In Kuwait, road traffic accidents (RTA) is the leading cause of death in young people. The study investigated the patterns of accidental deaths in Kuwait, one of the Gulf States which incorporates a wide variety of multi-ethnic communities. METHODS: The study was retrospective from 2003-2009. Data of forensic cases were collected from the general department of criminal evidence (GDCE) in the ministry of interior (MOI).We attempted to find out causes of accidental death and the prevelance of each cause. Furthermore, the relationship of demographic factors (eg. Age, sex, marital status and nationality) with each cause of accidental death in Kuwait were studied. RESULTS: The material of this study constituted a total of 4886 reported accidental deaths referred for Medico-legal examination. Road traffic accidents was by far the most prevalent cause of death (64.6%) followed by fall from height (13.1%). Poisoning and mine explosions were amongst the least common causes. CONCLUSION: The government of Kuwait needs to take strong measures to promote safety in the workplace and households by educational campaigns.

Forensic autopsy practice in the Middle East: comparisons with the west.

Autopsies are performed in the majority of Arab, Muslim countries. Several of these countries face social challenges and others do not have well established academic programs to teach the science. In this article we intend to review the history and practice of the forensic part of autopsies in a few Arab, Muslim countries (Egypt, Kingdom of Saudi Arabia (KSA) and Kuwait) and compare it with the United States of America (USA) and the United Kingdom (UK), 2 countries where the practice of forensic science and Forensic pathology is well established. This was achieved by pub med literature search and the distribution of a questionnaire to colleagues in Arab countries. We recommend that Arab countries explore the field of virtual autopsy to overcome some of the social challenges related to dissection of the cadaver. Kuwait can benefit from the introduction of Forensic training given the high workload in the country.

Metastatic medullary thyroid carcinoma to the breast in a patient with combined medullary and papillary carcinoma of thyroid--a case report.

We report the fine-needle aspiration cytology of a case of medullary thyroid carcinoma (MTC) metastatic to the breast in a 66-year old female within two years of diagnosis of the thyroid tumor. The aspirate of the breast metastases revealed a plasmacytoid population of cells in loose clusters and singly with mild to moderate pleomorphism. Nuclear groves and occasional intranuclear cytoplasmic inclusions were seen. The cells stained positive for calcitonin and negative for thyroglobulin. Use of immunocytochemical methods proved useful to diagnose metastasis which was essential in planning treatment. Cases of metastatic MTC to the breast diagnosed on fine-needle aspirates reported in the literature are reviewed.

Molecular characterization of a population-based series of endometrial stromal sarcomas in Kuwait.

Endometrial stromal sarcomas (ESSs) frequently harbor genetic fusions, including JAZF1-SUZ12 and equivalent fusions in low-grade ESS (LGESS) and YWHAE-NUTM2 in high-grade ESS (HGESS). This study aims to classify a population-based series of ESSs in Kuwait based on the 2014 World Health Organization classification system and to assess the diagnostic use of interferon-induced transmembrane protein 1 (IFITM1) immunomarker for ESSs. Twenty ESSs including 19 LGESSs and 1 HGESS treated during the period between 2002 and 2013 were identified, and the cases were reviewed and characterized using fluorescence in situ hybridization and immunohistochemical studies. Thirteen (81.3%) of 16 LGESSs with interpretable results showed JAZF1 and/or PHF1 genetic rearrangements by fluorescence in situ hybridization, and the only HGESS in the series showed YWHAE genetic rearrangement. All LGESSs with interpretable results showed positive immunostaining for CD10 compared with 11 (61%) of 18 that showed positive immunostaining for IFITM1; 4 of 7 IFITM1-negative LGESSs showed JAZF1 and/or PHF1 rearrangements. A series of uterine leiomyomas, leiomyosarcomas, adenosarcomas, and carcinosarcomas were included for comparison, and positive IFITM1 staining was found in 1 of 10 leiomyomas, 3 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 3 of 8 carcinosarcomas, compared to 0 of 10 leiomyomas, 9 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 5 of 8 carcinosarcomas that were positive for CD10. Our results demonstrated characteristic genetic rearrangements in a high percentage of LGESSs in this Middle Eastern population, and IFITM1 antibody appears to be less sensitive than CD10 for LGESS.

Contribution of immunocytochemical stainings for galectin-3, CD44, and HBME1 to fine-needle aspiration cytology diagnosis of papillary thyroid carcinoma.

In cytology practice some papillary thyroid carcinoma (PTC) cases have indeterminate diagnoses and overlapping cytological features with benign lesions. This study was undertaken to find out if immunocytochemistry using Galectin-3, CD-44 and HBME-1 could be of help in such situations. Forty-six cases consisting of 22 malignancy (PTC) cases, 7 suspicious of (S/O) PTC, 1 follicular neoplasm, 5 follicular lesion of undetermined significance (FLUS), and 11 benign (colloid goiter) cases diagnosed by FNA were included in this study. Staining reactions were graded in a sliding scale of -, 1+, 2+, 3+, and 4+. In an assessment of 100 cells, each cell with weak, and moderate to strong positive reaction were assigned a score of 1 and 4, respectively. Staining reaction of ≥+2 and scores >100 were considered positive. Frequency of cases with ≥+2 reaction, and scores >100 for each of Galectin-3, CD-44, and HBME-1 were significantly higher in PTC or combined PTC and S/O PTC cases as compared with FLUS and benign cases taken together (P = 0.01744 to 0.00000). When the cases were compared according to histological malignant and benign diagnoses, the difference was also significant in respect of ≥+2 reaction, and scores >100 for Galectin-3 and CD44 (P = 0.04923 to 0.00947); however, there was no significant difference, when these parameters for HBME1 were compared. Galectin 3, CD 44, and to some extent HBME 1 are useful immunocytochemical parameters with potential to support FNAC diagnosis of PTC, especially in situations with difficult differential diagnoses.

Patterns of infant mortality in Kuwait from 2003 to 2006.

Infant death is often tragic, particularly in the Arab World, where infants, especially males, are supposed to carry their family's names due to ancient cultural traditions. The conditions and events that may be associated with infant death are extremely varied. Infants may die from either congenital disorders or natural diseases, or may pass away as a consequence of a complicated delivery. Infants are also victims of accidents and violence such as homicides. The main aim of this study was to investigate the reported medico legal cases of infant mortality in Kuwait due to natural and un-natural causes between 2003 and 2006. The average IMR rate in Kuwait during the study period was better than the IMR average for developing countries and the IMR average for the world during the same study period. In general, these figures for Kuwait are even better than the average for Middle East and North Africa. More medico- legal cases were reported for deaths among Kuwaiti infants in 2004, 2005 and 2006 compared to non Kuwaiti infants. More Kuwaiti infants died due to RTA and domestic accidents. In contrast, only non Kuwaiti infant died from infanticide.

Effective therapy for acute antibody-mediated rejection with mild chronic changes: case report and review of the literature.

To reduce the long-term toxicities of immunosuppressant drugs, corticosteroid-sparing and calcineurin-inhibitor-sparing immunosuppression protocols have become increasingly popular in managing kidney transplant recipients. The most vexing clinical condition caused by antibodies in organ transplants is antibody-mediated rejection. Limitations of the current antibody-mediated rejection therapies include (1) antibody-mediated rejection reversal tends to be gradual rather than prompt, (2) expense, (3) rejection reversal rates below 80%, (4) common appearance of chronic rejection after antibody-mediated rejection treatment, and (5) long-term persistence of donor specific antibodies after therapy. Because these limitations may be due to a lack of effects on mature plasma cells, the effects of bortezomib on mature plasma cells may represent a quantum advance in antihumoral therapy. Our experiences represent the first clinical use of bortezomib as an antihumoral agent in renal allograft recipients in Kuwait. We present 2 cases with resistant-acute antibody-mediated rejection to the standard therapies that were managed successfully with bortezomib.

Isolated sarcoid renal granulomatous tubulointerstitial disease.

A 37-year-old lady presented with hypercalcemia and acute renal impairment. She had no previous medical problems apart from the use of non steroidal anti-inflammatory drugs for nonspecific body pains. Her abdominal ultrasound scan as well as urine studies were nonspecific. Further workup for hypercalcemia (skeletal survey, high resolution computed tomography (CT) of the chest and abdomen, purified protein derivative (PPD) test, serum protein electrophoresis, tumor markers, immunology screening, and Bence Jones proteinuria) was negative. Serum angiotensin converting enzyme was high. Renal biopsy showed extensive lymphocytes and multinucleated giant cells infiltration forming interstitial non necrotizing granulomata. Immune staining as well as staining for acid fast bacilli was negative. The possibility of sarcoid renal granulomata was raised and the patient was started on oral prednisolone with subsequent normalization of renal functions and serum calcium after one month of treatment.

Clinical and histopathological spectrum of IgA nephropathy in Kuwait.

BACKGROUND: Little is known about the nature and the course of IgA nephropathy (IgAN) in Arab countries. The aim of this work was to study the spectrum of clinical presentation and histopathological findings at our institution. DESIGN AND SETTING: Retrospective review, all renal biopsies at the Mubarak Al Kabeer Hospital between January 2000 and December 2004. METHODS: Cases of IgA nephropathy were selected, and their medical records and biopsy findings were reviewed. RESULTS: Eighty patients (9.2% of all native kidney biopsies) were diagnosed to have IgAN nephropathy. Sixty-nine biopsies were included in the study;11 were excluded. Forty-three (62.3%) patients were male and 26 (37.7) patients were female. Fifty (72.5%) patients were below the age of 40 years. Mean (SD) duration of follow-up was 3.6 (1.3) years. The first presentation included nephritic-range proteinuria (49.3%) and renal impairment (50.7%). During the follow-up period, 56 (81.2%) patients were stable or improved. Hass classification of biopsies showed 36.2% had class I, 27.5% had class II, 13.0% had class III, 5.8% had class IV, and 17.4% had class V IgAN. Females had milder forms of the disease than males. Macroscopic hematuria and renal impairment at presentation were seen more in patients with class IV and V IgAN. The presenting serum creatinine and uric acid values were higher in those with Hass classes III to V. Deterioration of renal function during the follow-up period was more significant in the presence of hypertension, renal impairment, or macroscopic hematuria at the time of biopsy . CONCLUSION: The prevalence of IgAN in Kuwait is about 9.2%. Renal impairment or macroscopic hematuria at presentation was seen in patients with more aggressive renal lesions and contributed to poor outcome.

Late acute antibody mediated rejection after nine years of renal transplantation.

Acute antibody mediated rejection (AMR) is rarely reported as a long-term com-plication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 45-year-old gentleman with chronic kidney disease due to unknown etiology received renal transplantation from his sister with 4 HLA mismatches. He received antithymocte globulin induction therapy and was maintained on steroids, azathioprine (AZA) and cyclosporine A (CsA). Up to eight years post-transplantation he was clinically and biochemically stable. He lost follow-up for about one year, and then presented with nephritic nephrotic syndrome and rise of serum creatinine (SCr.) to 210 µmol/L. Graft biopsy revealed picture suggestive of acute AMR on top of de novo membranoprolipherative glomerulonephritis (MPGN) with focal crescent formation, diffuse immune complex deposition and peritubular capillaries C4d positivity. Anti-HLA donor specific antibodies were highly positive for B and T cells class I and class II. The patient was treated with intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab). AZA was changed to mycophenolate mofetil and CsA to tacrolimus. He had partial response, but SCr. continued at 220 µmol/L.

Renal biopsy in patients with type 2 diabetes mellitus: indications and nature of the lesions.

BACKGROUND AND OBJECTIVES: The prevalence of non diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus varies widely depending on the selection criteria and the populations being studied. The aim of this study was to evaluate the renal biopsies performed on type 2 diabetic patients for suspicion of NDRD and to correlate the pathological with the clinical and laboratory findings. SUBJECTS AND METHODS: We selected and reviewed biopsies performed on type 2 diabetics for clinically suspected NDRD from January 2006 to December 2008 at a single hospital. Clinical and laboratory data were analyzed in relation to the histopathology findings. Patients were grouped into either group I with isolated DGS or group II with NDRD on top of DGS. RESULTS: Thirty-one biopsies were performed on type 2 diabetic patients; Seventeen patients (54.8%) were males. Mean age was 50.68 (11.29) years. The mean duration of diabetes was 9.33 (3.6) years. Renal biopsy showed that among the studied group 14 patients (45.2%) showed NDRD on top of DGS. Crescentic glomerulonephritis was the commonest finding seen in 3 cases (21.4% of group II cases) followed by acute tubulointerstitial nephritis and hypertensive changes each was seen in 2 cases (14.4%). Other findings included IgA nephropathy, primary focal segmental glomerulosclerosis, rhabdomyolysis, membranoproliferative glomerulonephritis each of them was seen in one case (7.1%). Group I had a significantly higher level of proteinuria 4.97 (2.08) gm/24 hrs urine than group II 2.72 (1.09) gm/24 hrs urine (P=.003). There was no significant difference between the two groups in age, duration of diabetes, gender, presence of hypertension, hematuria, serum creatinine or glomerular filtration rate. CONCLUSION: The present study showed that crescentic glomerulonephritis is the commonest NDRD among diabetic patients. A higher level of proteinuria was reported among those with NDRD superimposed on DGS. So, Renal biopsy should be performed in diabetics when the clinical scenario is atypical.

Disseminated peritoneal Schistosoma japonicum: a case report and review of the pathological manifestations of the helminth.

Schistosomiasis (also known as bilharzia, bilharziasis, bilharziosis or snail fever) is a human disease syndrome caused by infection from one of several species of parasitic trematodes of the genus Schistosoma. The three main species infecting humans are S haematobium, S japonicum, and S mansoni. S japonicum is most common in the far east, mostly in China and the Philippines. We present an unusual case of S japonicum in a 32-year-old Filipino woman who had schistosomal ova studding the peritoneal cavity and forming a mass in the right iliac fossa.