Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Lung metastases in low-risk gestational trophoblastic neoplasia: a retrospective cohort study.

OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.

Risk factors for rehospitalization for patients following release from court-ordered evaluation: A retrospective study.

We have noticed an increase in the number of patients who go through the court-ordered evaluation (COE) process but are not placed on a court-ordered treatment, and who then return to the hospital on another COE petition within one year from their initial discharge. The aim of this study is to examine what factors might be involved in rehospitalization in this population of psychiatric patients. The records of 146 readmitted patients and 146 randomized patients not readmitted were compared for various risk factors. Data were analyzed using univariate and mutivariate procedures. All patients who had diagnoses of substance-induced mood or psychotic disorders were readmitted within one year. Other risk factors included younger age, seriously mentally ill (SMI) status, longer length of stay and having a psychotic or schizophrenia spectrum disorder. Substance-induced mood or psychotic disorder may play significant roles for patients who are rehospitalized within a year of initial COE.

Management and prognostic factors of epithelioid trophoblastic tumors: Results from the International Society for the Study of Trophoblastic Diseases database.

OBJECTIVE: Epithelioid Trophoblastic Tumor (ETT) is an extremely rare form of Gestational Trophoblastic Neoplasia (GTN). Knowledge on prognostic factors and optimal management is limited. We identified prognostic factors, optimal treatment, and outcome from the world's largest case series of patients with ETT. METHODS: Patients were selected from the international Placental Site Trophoblastic Tumor (PSTT) and ETT database. Fifty-four patients diagnosed with ETT or mixed PSTT/ETT between 2001 and 2016 were included. Cox regression analysis was used to identify prognostic factors for overall survival (OS). RESULTS: Forty-five patients with ETT and 9 patients with PSTT/ETT were included. Thirty-six patients had FIGO stage I and 18 had stages II-IV disease. Patients were treated with surgery (n = 23), chemotherapy (n = 6), or a combination of surgery and chemotherapy (n = 25). In total, 39 patients survived, including 22 patients with complete sustained hCG remission for at least 1 year. Patients treated with surgery as first line treatment had early-stage disease and all survived. Most patients treated with chemotherapy with or without surgery had FIGO stages II-IV disease (55%). They underwent multiple lines of chemotherapy. Eleven of them did not survive. Interval since antecedent pregnancy and FIGO stage were prognostic factors of OS (p = 0.012; p = 0.023 respectively). CONCLUSIONS: Advanced-stage disease and an interval of ≥48 months since the antecedent pregnancy are poor prognostic factors of ETT. Surgery seems adequate for early-stage disease with a shorter interval. Advanced-stage disease requires a combination of treatment modalities. Because of its rarity, ETT should be treated in a centre with experience in GTN.

Can the FIGO 2000 scoring system for gestational trophoblastic neoplasia be simplified? A new retrospective analysis from a nationwide dataset.

BACKGROUND: Worldwide introduction of the International Fedaration of Gynaecology and Obstetrics (FIGO) 2000 scoring system has provided an effective means to stratify patients with gestational trophoblastic neoplasia to single- or multi-agent chemotherapy. However, the system is quite elaborate with an extensive set of risk factors. In this study, we re-evaluate all prognostic risk factors involved in the FIGO 2000 scoring system and examine if simplification is feasible. PATIENTS AND METHODS: Between January 2003 and December 2012, 813 patients diagnosed with gestational trophoblastic neoplasia were identified at the Trophoblastic Disease Centre in London and scored using the FIGO 2000. Multivariable analysis and stepwise logistic regression were carried out to evaluate whether the FIGO 2000 scoring system could be simplified. RESULTS: Of the eight FIGO risk factors only pre-treatment serum human chorionic gonadotropin (hCG) levels exceeding 10 000 IU/l (OR = 5.0; 95% CI 2.5-10.4) and 100 000 IU/l (OR = 14.3; 95% CI 4.7-44.1), interval exceeding 7 months since antecedent pregnancy (OR = 4.1; 95% CI 1.0-16.2), and tumor size of over 5 cm (OR = 2.2; 95% CI 1.3-3.6) were identified as independently predictive for single-agent resistance. In addition, increased risk was apparent for antecedent term pregnancy (OR = 3.4; 95% CI 0.9-12.7) and the presence of five or more metastases (OR = 3.5; 95% CI 0.4-30.4), but patient numbers in these categories were relatively small. Stepwise logistic regression identified a simplified risk scoring model comprising age, pretreatment serum hCG, number of metastases, antecedent pregnancy, and interval but omitting tumor size, previous failed chemotherapy, and site of metastases. With this model only 1 out 725 patients was classified different from the FIGO 2000 system. CONCLUSION: Our simplified alternative using only five of the FIGO prognostic factors appears to be an accurate system for discriminating patients requiring single as opposed to multi-agent chemotherapy. Further work is urgently needed to validate these findings.

Physical Rehabilitation Subsequent to Fixation of Ilizarov Ring Fixator for the Management of Distal Femur Fracture: A Case Report.

Distal femur fractures are severe all over the world. The goal of the study was to assess the effect of physiotherapy on ROM, strength, and improving quality of life. Due to the anatomy of distal femur fracture, the Ilizarov ring fixator is useful as it helps maintain mobility and stability. Distal femur fractures are most treated surgically compared to non-surgical treatment. The use of external fixators differs according to the patient's condition and the stability of the patient. This study's objective was to evaluate the effectiveness of an evidence-based procedure prepared for the management of distal femur fracture and chronic osteomyelitis femur. In some cases, due to discharging sinus, the patient requires long-term treatment followed by a home physiotherapy rehabilitation program. The objective was to assess the effects of Ilizarov circular external fixators (ICEF) on distal femur fracture.

Physiotherapy Rehabilitation Following Acoustic Neuroma Resection in a Patient With Cerebellopontine Angle Tumour: A Case Report.

Acoustic neuroma excision in patients with cerebellopontine angle (CPA) tumours offers particular rehabilitation problems due to the complicated architecture of the cerebellum and brainstem tissues involved. CPA tumours (acoustic neuromas) are slow-growing tumours that arise from the vestibulocochlear nerve. Surgical excision of these tumours can cause neurological abnormalities that compromise motor coordination, balance, and facial nerve function. The case study emphasises the importance of a comprehensive physiotherapeutic approach in rehabilitating a patient following acoustic neuroma excision, with a focus on particular CPA tumour deficits. The rehabilitation programme focuses on improving functional outcomes through balance, proprioception, and vestibular rehabilitation that is customised to the demands and deficiencies of the patient. Our comprehensive approach seeks to improve patients' quality of life, promote neurological healing, and support easy reintegration into normal activities following CPA tumour surgery.

Physical Therapy Interventions: A Case Report of Building Strength, Confidence, and Mobility in a Seven-Year-Old With Congenital Femoral Deficiency With Coxa Vara.

Congenital femoral deficiency (CFD) and congenital coxa vara (CCV) are rare conditions characterized by abnormal development of the femur and hip joint, respectively. This case report documents the rehabilitation journey of a seven-year-old child diagnosed with CFD and CCV, highlighting the efficacy of physical therapy interventions in enhancing strength, balance, normal gait patterns, confidence, and mobility. Through a comprehensive physiotherapy regimen tailored to the specific needs of the patient, significant improvements in muscle strength, joint stability, and functional mobility were observed over the course of treatment. Moreover, the implementation of targeted exercises and adaptive strategies not only facilitated physical gains but also contributed to bolstering the child's confidence and overall quality of life. This case underscores the pivotal role of physiotherapy in addressing the complex challenges associated with congenital orthopedic anomalies, ultimately fostering independence and well-being in pediatric patients.

Progressive Physiotherapy Rehabilitation Program for a Patient With Biceps Tenodesis Recovery: A Case Report.

The present case report investigates the effectiveness of a progressive physiotherapy rehabilitation program in aiding the recovery of a patient who underwent biceps tenodesis. It is a surgical procedure involving the reattachment or relocation of the biceps tendon to alleviate pain and enhance function in conditions, like tendinitis or tears. The rehabilitation program is specifically tailored to address the distinct challenges associated with biceps tenodesis recovery, focusing on gradual exercises aimed at improving strength, range of motion (ROM), and functional capacity. Through a comprehensive analysis, this case report seeks to offer insights into the potential advantages and obstacles of employing a specialized physiotherapy approach in the holistic care of individuals undergoing biceps tenodesis, contributing to the ongoing development of postoperative rehabilitation strategies.

Germ cell cancer in pregnancy - Successfully treated with chemotherapy and surgery.

A 31-year-old primigravida, with spontaneous singleton pregnancy, presented in 21 weeks of gestation with abdominal pain. Abdominal ultrasound (USS) and Magnetic Resonance Imaging (MRI) showed a 12 × 14cm large complex lesion arising from the right ovary suspicious for an ovarian malignancy. The radiological staging demonstrated no further metastatic disease; however, it also revealed a 6 cm lesion in the contralateral ovary, consistent with a dermoid cyst. After tumour board discussion the patient underwent a mid-line laparotomy with right oophorectomy, cytology, and peritoneal and omental staging, under oral tocolysis with indomethacin. The left presumed ovarian dermoid was left in situ to avoid additional surgical and obstetrical morbidity. Histology confirmed a grade 3 immature teratoma with primitive neuroepithelium focally present on the capsular surface and atypical cells in the cytology amounting to a stage 1 C2 disease at least. Due to high-risk disease, she was offered adjuvant treatment. The patient received one cycle of intravenous paclitaxel, etoposide, and cisplatin chemotherapy, in an adjuvant setting. She underwent an elective caesarean section at 36 weeks, with the safe delivery of a healthy baby girl. After 6 weeks of her delivery, she received three further cycles of etoposide, and cisplatin to complete her course of adjuvant chemotherapy. Three months after the last chemotherapy cycle, she underwent a laparoscopic removal of the left ovarian dermoid that had increased in size to 8 cm. Final histology revealed no immature elements. To this point, 2 years after initial diagnosis, both mother and child are healthy with no long-term complications. The patient has resumed her normal menstrual cycle and being in remission, she wishes soon to try for a second child. To our knowledge, this is the only reported case of ovarian immature teratoma in pregnancy treated successfully with surgery and adjuvant iv paclitaxel, etoposide, and cisplatin chemotherapy regime.

Effect of Physiotherapy on a Rare Case of Malunion of Femur and Patellar Fracture in a 43-Year-Old Male: A Case Report.

The hip is a ball-and-socket joint surrounded by strong and well-balanced muscles that allow for a wide range of motion in many physical planes. Iliofemoral, ischiofemoral, and pubofemoral are the three major ligaments of the hip joint that provide stability to the joint. Supracondylar femoral fractures are common in old age and can be caused in young people due to accidents or traumatic causes. These types of fractures are complicated to fix surgically due to different architectural designs. If not treated appropriately, these can cause malunion or non-union of the joint. The knee joint is a synovial joint of the hinge type. It has two major degrees of movement, which are flexion and extension. However, rotation in both the medial and lateral directions is possible to some extent in the joint. Patellar fractures can be transverse, vertical, comminuted, marginal, or osteochondral. In this case report, we present a 43-year-old male patient who had a history of falling from a bike. He was diagnosed with a comminuted supracondylar fracture of the left femur and a comminuted fracture of the patella on the left side on an X-ray. For this, he was managed with open reduction, internal fixation, and vacuum-assisted closure (VAC). Physiotherapy rehabilitation was programmed to attain a good and fast recovery for the patient to make him functionally independent and improve his quality of life.

Reversible acute kidney injury (AKI) by active removal of serum light chains in an HIV positive patient with myeloma kidney.

BACKGROUND: The association of HIV and myeloma has rarely been reported in the literature. This following case discusses the presentation of acute kidney injury (AKI) in a 53-year-old lady with HIV, subsequently diagnosed with myeloma. Furthermore, we describe recovery of renal function and dialysis independence using a combination of light chain removal by dialysis with a high cut-off dialyzer and chemotherapy. INVESTIGATIONS: Physical examination, urine, blood tests, renal biopsy, bone marrow aspirate and trephine, US scan. DIAGNOSIS: Myeloma. MANAGEMENT: Dialysis and chemotherapy.

Resveratrol protects against inorganic arsenic-induced oxidative damage and cytoarchitectural alterations in female mouse hippocampus.

Prolonged inorganic arsenic (iAs) exposure is widely associated with brain damage particularly in the hippocampus via oxidative and apoptotic pathways. Resveratrol (RES) has gained considerable attention because of its benefits to human health. However, its neuroprotective potential against iAs-induced toxicity in CA1 region of hippocampus remains unexplored. Therefore, we investigated the neuroprotective efficacy of RES against arsenic trioxide (As2O3)-induced adverse effects on neuronal morphology, apoptotic markers and oxidative stress parameters in mouse CA1 region (hippocampus). Adult female Swiss albino mice of reproductive maturity were orally exposed to either As2O3 (2 and 4 mg/kg bw) alone or in combination with RES (40 mg/kg bw) for a period of 45 days. After animal sacrifice on day 46, the perfusion fixed brain samples were used for the observation of neuronal morphology and studying the morphometric features. While the freshly dissected hippocampi were processed for biochemical estimation of oxidative stress markers and western blotting of apoptosis-associated proteins. Chronic iAs exposure led to significant decrease in Stratum Pyramidale layer thickness along with reduction in cell density and area of Pyramidal neurons in contrast to the controls. Biochemical analysis showed reduced hippocampal GSH content but no change in total nitrite (NO) levels following iAs exposure. Western blotting showed apparent changes in the expression levels of Bax and Bcl-2 proteins following iAs exposure, however the change was statistically insignificant. Contrastingly, iAs +RES co-treatment exhibited substantial reversal in morphological and biochemical observations. Together, these findings provide preliminary evidence of neuroprotective role of RES on structural and biochemical alterations pertaining to mouse hippocampus following chronic iAs exposure.

Increasing the human chorionic gonadotrophin cut-off to ≤1000 IU/l for starting actinomycin D in post-molar gestational trophoblastic neoplasia developing resistance to methotrexate spares more women multi-agent chemotherapy.

BACKGROUND: A human chorionic gonadotropin (hCG) cut-off of ≤300 IU/l for starting actinomycin D (ActD) in post-molar gestational trophoblastic neoplasia (GTN) patients developing methotrexate resistance (MTX-R) reduced the number of women needing toxic multi-agent chemotherapy (etoposide, MTX and ActD alternating weekly with cyclophosphamide and vincristine; EMA/CO) without affecting survival. Here we assess whether an increased hCG cut-off of ≤1000 IU/l spares more women EMA/CO. PATIENTS AND METHODS: All post-molar GTN patients treated with first-line methotrexate and folinic acid (MTX/FA) were identified in a national cohort between 2009 and 2016. Data collected included age, FIGO score, the hCG levels at MTX-R, and treatment outcomes. RESULTS: In total, 609 GTN patients commenced treatment with MTX/FA achieving a complete response in 57% (348/609). Resistance developed in 25.1% (153/609) at an hCG ≤ 1000 IU/l and switching to ActD achieved remission in 92.8% without any major toxicity with the remaining 7.2% remitting on EMA/CO. Comparative analysis of patients switching at an hCG <100 versus 100-300 versus 300-1000 IU/l revealed a significant fall in the cure rate with second-line ActD from 97% (93/96) to 87% (34/39) to 78% (14/18), respectively, P = 0.009. However, by increasing the hCG cut-off from ≤300 to ≤1000 IU/l, 14 patients were spared EMA/CO chemotherapy. Moreover, in the present series, all post-molar GTN remain in remission. CONCLUSION: This study demonstrates that increasing the hCG cut-off from ≤300 to ≤1000 IU/l for choosing patients for ActD following MTX-R spares more women with GTN from the greater toxicity of EMA/CO without compromising 100% survival outcomes.

Treatment of metastatic placental site trophoblastic tumor with surgery, chemotherapy, immunotherapy and coil embolization of multiple pulmonary arteriovenous fistulate.

Placental Site Trophoblastic Tumor (PSTT) is a rare malignancy that often presents with extensive disease and can be resistant to traditional treatments. We present the case of a woman with stage IV PSTT who was initially managed with neoadjuvant chemotherapy followed by tumor debulking. Adjuvant therapy was guided by further pathologic analysis that revealed high levels of staining for PD-L1 as well as the presence of tumor infiltrating lymphocytes (TILs). Subsequently, the patient was treated with traditional chemotherapy with the EP/EMA regimen with the addition of pembrolizumab. The patient's treatment course was complicated by the development of pulmonary arteriovenous malformations, autoimmune thyroiditis thought to be secondary to immunotherapy, and significant tinnitus secondary to platinum agents. Currently the patient is in follow up and remains in a complete remission.

Wound contraction effects and antibacterial properties of Tualang honey on full-thickness burn wounds in rats in comparison to hydrofibre.

BACKGROUND: Full-thickness burn wounds require excision and skin grafting. Multiple surgical procedures are inevitable in managing moderate to severe full-thickness burns. Wound bed preparations prior to surgery are necessary in order to prevent wound infection and promote wound healing. Honey can be used to treat burn wounds. However, not all the honey is the same. This study aims to evaluate the wound contraction and antibacterial properties of locally-produced Tualang honey on managing full-thickness burn wounds in vivo. METHODS: Thirty-six female Sprague Dawley rats were randomly divided into three groups. Under anaesthesia, three full-thickness burn wounds were created on the dorsum of the rats. The full-thickness burn wounds were inoculated with a specific organism (10(4)), namely Pseudomonas aeruginosa (n = 12), Klebsiella pneumoniae (n = 12), or Acinetobacter baumannii (n = 12). The three burn wounds were dressed with Tualang honey, hydrofibre and hydrofibre silver respectively. Swab samples were obtained every 3 days (day 3, 6, 9, 12, 15, 18 and 21) for quantitative and semi-quantitative microbiological analyses. Clinical assessments, including observations concerning the appearance and wound size, were measured at the same time. RESULTS: There was a rapid 32.26% reduction in wound size by day 6 (p = 0.008) in the Tualang honey-treated wounds, and 49.27% by day 15 (p = 0.005). The wounds remained smaller by day 18 (p < 0.032). Tualang honey-treated rats demonstrated a reduction in bacterial growth in Pseudomonas aeruginosa inoculated wounds (p = 0.005). However, hydrofibre silver and hydrofibre-treated wounds are superior to honey-treated wounds with Acinetobacter baumannii (p = 0.035). There was no statistical significant of antibacterial property in Klebsiella pneumonia inoculated wounds. CONCLUSIONS: Tualang honey has better results with regards to its control of Pseudomonas aeruginosa and its wound contraction effects on full-thickness burn wound in vivo.

Anaesthesia for ear surgery in remote or resource-constrained environments.

BACKGROUND: The successful provision of middle-ear surgery requires appropriate anaesthesia. This may take the form of local or general anaesthesia; both methods have their advantages and disadvantages. Local anaesthesia is simple to administer and does not require the additional personnel required for general anaesthesia. In the low-resource setting, it can provide a very safe and effective means of allowing middle-ear surgery to be successfully completed. However, some middle-ear surgery is too complex to consider performing under local anaesthesia and here general anaesthesia will be required. CONCLUSION: This article highlights considerations for performing middle-ear surgery in a safe manner when the available resources may be more limited than those expected in high-income settings. There are situations where local anaesthesia with sedation may prove a useful compromise of the two techniques.