CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Individualised Estimation of Quality-adjusted Survival Benefit and Cost-effectiveness of Proton Beam Therapy in Intermediate-stage Hodgkin Lymphoma.

AIMS: Radiotherapy for Hodgkin lymphoma leads to the irradiation of organs at risk (OAR), which may confer excess risks of late effects. Comparative dosimetry studies show that proton beam therapy (PBT) may reduce OAR irradiation compared with photon radiotherapy, but PBT is more expensive and treatment capacity is limited. The purpose of this study is to inform the appropriateness of PBT for intermediate-stage Hodgkin lymphoma (ISHL). MATERIALS AND METHODS: A microsimulation model simulating the course of ISHL, background mortality and late effects was used to estimate comparative quality-adjusted life years (QALYs) lived and healthcare costs after consolidative pencil beam scanning PBT or volumetric modulated arc therapy (VMAT), both in deep-inspiration breath-hold. Outcomes were compared for 606 illustrative patients covering a spectrum of clinical presentations, varying by two age strata (20 and 40 years), both sexes, three smoking statuses (never, former and current) and 61 pairs of OAR radiation doses from a comparative planning study. Both undiscounted and discounted outcomes at 3.5% yearly discount were estimated. The maximum excess cost of PBT that might be considered cost-effective by the UK's National Institute for Health and Care Excellence was calculated. RESULTS: OAR doses, smoking status and discount rate had large impacts on QALYs gained with PBT. Current smokers benefited the most, averaging 0.605 undiscounted QALYs (range -0.341 to 2.171) and 0.146 discounted QALYs (range -0.067 to 0.686), whereas never smokers benefited the least, averaging 0.074 undiscounted QALYs (range -0.196 to 0.491) and 0.017 discounted QALYs (range -0.030 to 0.086). For the gain in discounted QALYs to be considered cost-effective, PBT would have to cost at most £4812 more than VMAT for current smokers and £645 more for never smokers. This is below preliminary National Health Service cost estimates of PBT over photon radiotherapy. CONCLUSION: In a UK setting, PBT for ISHL may not be considered cost-effective. However, the degree of unquantifiable uncertainty is substantial.

Deep vein thrombosis and euvolemic hyponatremia in a hypothyroid patient.

Hypothyroidism is a procoagulant state; hypothyroid females have greater risk of DVT than hypothyroid males. We present a case of primary hypothyroidism who presented with euvolemic hyponatremia and DVT that required thyroxine replacement and correction of hyponatremia. This highlights that hypothyroidism can present as euvolemic hyponatremia and deep vein thrombosis.

Platelet-Rich Plasma and Platelet-Rich Fibrin as a Regenerative Tool.

Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are used as a valuable adjunct in the treatment of maxillofacial rehabilitation. PRP used along with growth hormone helps in bone healing and tissue regeneration in the areas affected by bone and soft tissue-related defects. It aids not only in faster and better healing of the surgically debrided area but also in regeneration of the bone at a faster rate. This review comprises the applications of PRP and PRF and their uses in various procedures.

Mollaret's meningitis. A variant of recurrent hereditary polyserositis, both provoked by metaraminol.

Mollaret's meningitis is a rare condition with a characteristic clinical and cerebrospinal fluid picture. In many ways it resembles recurrent hereditary polyserositis (familial Mediterranean fever) in its natural history, pattern of attacks, and response to colchicine. Association of the two conditions has been reported, so far, in two patients only. In our patient the symptoms of both conditions were induced by a metaraminol provocative infusion. We have previously introduced this as a specific diagnostic and confirmatory test for recurrent hereditary polyserositis. The possibility that the two conditions represent different manifestations of a single disease is therefore strengthened.

Comparative trial of valproate sodium and clonazepam in chronic epilepsy.

A crossover comparative study of valproate sodium and clonazepam in the treatment of 32 adult epileptic patients receiving multiple drug therapy is described. Serum concentrations of other anticonvulsant drugs were unchanged by the addition of clonazepam. However, patients receiving high doses of other anticonvulsant drugs had lower serum concentrations of clonazepam (p less than .01). With valproate sodium, phenobarbital concentrations increased (P less than .05) in patients receiving phenobarbital but not significantly in patients receiving primidone. Phenytoin concentrations were reduced (P less than .05) during treatment with valproate sodium. Both drugs significantly reduced the frequency of minor seizures, with valproate sodium having the greater effect. However, it is important to monitor serum concentrations of other anticonvulsant drugs during treatment with valproate sodium since changes in these may influence seizure control or cause side effects.

Effectiveness of sodium valproate in the treatment of Sydenham's chorea.

We treated 15 children with Sydenham's chorea with sodium valproate at a dose of 15 to 20 mg/kg/d. In 13 of them the chorieform movements disappeared within 1 week of therapy. The remaining 2 had incomplete response. Two patients relapsed; 1 of them responded to the reintroduction of valproate. The mean duration of treatment was 6.7 weeks. We observed no major side effects. This study strongly suggests that valproate is an effective drug in the treatment of Sydenham's chorea.

Rapid diagnosis of central nervous system brucellosis by ELISA.

The diagnosis of central nervous system (CNS) brucellosis was made by determining Brucella-specific IgG, IgM and IgA in cerebrospinal fluid (CSF) specimens, using an enzyme-linked immunosorbent assay (ELISA) method. A total of 68 CSF specimens including 10 from patients with brucellosis of the nervous system, 4 with Brucella infection but without CNS involvement, 38 with meningitis other than due to Brucella and 16 with no meningitis were studied. Of the 10 CSF specimens from patients with CNS brucellosis, Brucella-specific IgG was detected in all 10, IgM in 7 and IgA in 8. The 10 patients were also seropositive for anti-Brucella IgG and IgM, and 9 were seropositive for IgA. No Brucella-specific IgG, IgM or IgA was detected in the CSF of 4 patients with brucellosis but without CNS involvement, even though the blood of these patients had high titres of anti-Brucella IgG, IgM and IgA. In addition, none of the CSF specimens from the 38 patients with meningitis other than due to Brucella, or from the 16 patients without meningitis, had detectable anti-Brucella antibodies. This study indicates that the Brucella ELISA on CSF is a reliable, rapid, sensitive and specific assay in the diagnosis of CNS brucellosis.

A study of age-dependent changes in thyroid function tests in adults.

Total serum thyroxine (T4), triiodothyronine (T3), T3 resin uptake (T3U), thyrotrophin (TSH), and reverse T3 (rT3) were measured in 209 healthy adults 20--89 yr old. Mean T4 values for men were stable throughout life, but in females under age 60, T4 values were significantly higher than in older women. Values for T3U in males were significantly higher than in females throughout all decades, although females had a significant increase in T3U after age 60. TSH values increased significantly in females over age 60. Throughout all decades, males had stable TSH levels that were slightly higher than the female results before age 60 and lower thereafter. Mean serum T3 declined similarly for both sexes with increasing age, although not to the extent previously reported. Men had significantly higher mean rT3 values over all decades than females, although female rT3 levels decreased after age 50 whereas males maintained stable values. The physiologic reasons for these findings may be due to sex-related changes in binding proteins and alterations in metabolic clearance rates, production, and degradation of these hormones with increasing age.

ELISA versus routine tests in the diagnosis of patients with systemic and neurobrucellosis.

Sera from patients in different stages of brucellosis as well as sera and cerebrospinal fluid (CSF) from patients with central nervous system (CNS) brucellosis and controls, were tested by ELISA for Brucella-specific IgG, IgM and IgA. The results were compared with culture findings, micro-agglutination (MA), slide agglutination with Rose Bengal (RB), and Brucella melitensis stained antigens (SA). In sera of patients with acute brucellosis (296), ELISA was positive for IgM (100%), IgG (97%) and IgA (98%), and comparable results were found in sera of patients with subacute brucellosis (44): IgG (100%), IgM (86%) and IgA (100%). However, in patients with chronic brucellosis (40), IgG and IgA were consistently positive (100%) while IgM was only positive in 33% of their sera. The MA and RB showed similar results, being more positive in patients with acute (98%) and subacute (84%) than in chronic (61%) brucellosis. The SA and culture showed significantly lower positive results. In the CSF of patients with CNS brucellosis (45), ELISA was positive in 100%, 20% and 85% for IgG, IgM and IgA, respectively, compared to 13% positive by culture, 25% by MA and 22% by RB. ELISA was negative in the CSF specimens from patients with brucellosis without CNS involvement (66), or meningitis other than Brucella (62), and no meningitis (144). Thus, ELISA with its IgG, IgM and IgA profiles is the test of choice in the diagnosis of patients with brucellosis, especially those with chronic or CNS infection.

New variant Creutzfeldt-Jakob disease.

Since the report of new variant Creutzfeldt-Jakob Disease (nvCJD) in humans last year, the search was on for direct evidence to link the condition to Bovine Spongiform Encephalopathy (BSE). The first case nvCJD was noted 10 years after the recognition of BSE in UK cattle. A direct link is now established. There are, however, some 'protective' mechanisms, the most important of which are the inefficiency of the gastric route of introducing the infected material, the species barrier and genetic 'predisposition'. None of these is full proof and time will tell whether feeding ruminants with their own species will turn out to be a major public health disaster?

Brainstem auditory evoked potential (BAEP) abnormalities in brucellosis.

Twelve patients with neurobrucellosis and 17 patients with systemic brucellosis without neurological involvement underwent a brainstem auditory evoked potentials (BAEP) study. All neurobrucellosis patients (100%) showed abnormalities in their BAEP recordings, suggestive of brainstem lesions at various levels. On the other hand, only 5 (29%) of the 17 patients with systemic brucellosis had mild unilateral BAEP abnormalities, while the remaining 12 had normal responses. Comparison of pooled data between the systemic brucellosis and neurobrucellosis groups showed highly significant differences in all BAEP parameters. The recording of BAEP is thus considered a sensitive supplementary method to reveal CNS lesions in patients with neurobrucellosis.

The role of folate deficiency in the development of peripheral neuropathy caused by anticonvulsants.

To investigate the role of folate deficiency in neuropathy caused by anticonvulsants, electrophysiological studies of peripheral nerve function were carried out on 29 epileptic patients on long-term anticonvulsant therapy. All but three patients showed abnormalities in one or more electrophysiological measurements, the main abnormality being in amplitude of sensory nerve action potential--this was reduced or absent in 76% of patients. All patients had low concentrations of folate in serum and CSF, these being below the normal ranges in 19 patients. These 19 patients were treated with folate, either 5-formyltetrahydrofolate (10 patients) or folic acid (9 patients), over a period of one month. After therapy all patients had normal levels of folate in serum and CSF, slightly higher levels in CSF being obtained in those receiving 5-formyltetrahydrofolate. Folate therapy significantly reversed abnormalities in motor and sensory nerve distal latencies; the effect was greater with 5-formyltetrahydrofolate, apparently because this produced higher CSF folate concentrations than folic acid. We conclude that folate deficiency may be involved in the development of peripheral neuropathy due to anticonvulsants.

Brainstem auditory evoked potentials in Wilson's disease.

Twelve patients with Wilson's disease, aged 11-25 years, underwent brainstem auditory evoked potential (BAEP) study. The results were correlated to clinical, neuroradiological and laboratory data. Ten had prominent to severe neurological manifestations, suggestive of involvement of one or several CNS structures, and 2 were neurologically free. All had evidence of abnormal copper metabolism, and 8 had CT scan evidence of brain atrophy, or hypodense areas in basal ganglia, or both. The 2 patients without neurological manifestations as well as one with neurological signs had normal BAEP. One patient with neurological signs had increased N1 latency due to cochlear hearing loss, but normal interpeak intervals, while 8 of 10 patients with prominent neurological symptoms and signs had abnormal BAEPs (prolongation of NIII-NV interpeak interval). The value of NIII-NV interpeak interval correlated with the number of different neurological signs (neurological score) attributable to involvement of different CNS structures (r = 0.64 at P = 0.001). Abnormal BAEPs do not seem to be an early finding in Wilson's disease.

Epidemiology of multiple sclerosis in Arabs in Kuwait: a comparative study between Kuwaitis and Palestinians.

On December 31, 1988 there were 201 registered multiple sclerosis patients in Kuwait, an overall prevalence rate (PR) of 10.2 per 100,000; among them were 186 Arabs, of whom 72 were Palestinians and 51 Kuwaitis. Comparison of these two subgroups, who had a similar age distribution revealed that the disease was 2 1/2 times more frequent among Palestinians (PR 23.8/100,000) than among Kuwaitis (PR 9.5/100,000). Palestinians also showed significant differences from Kuwaitis in eye color, blood group distribution and HLA-DR and HLA-DQW epitopes frequency. This suggests that genetic rather than environmental factors might be the underlying cause for the high susceptibility to develop MS among Arabs originating from the Eastern Mediterranean basin.

Surgery in combined pulmonary and neural cryptococcosis.

A 39-year-old previously healthy patient with combined pulmonary and neural cryptococcosis was successfully managed by pulmonary resection and antifungal chemotherapy. The pulmonary mass was removed under cover of miconazole and 5-fluorocytosine even though the patient had concomitant active meningitis. He recovered dramatically after the surgical procedure and remained well 2 years later. We suggest that, as in our patient, early removal of a pulmonary cryptococcal mass under antifungal cover may in other similar patients obviate the need for protracted antifungal therapy and lead to an excellent response of the neural cryptococcosis.

Spontaneous intracranial hypotension: clinical and magnetic resonance imaging characteristics.

The syndrome of spontaneous intracranial hypotension (SIH) is an uncommon cause of postural headache. We describe three patients with classical low pressure headache associated with low CSF pressure, one of whom presented with sudden deafness and another with a unilateral VIth nerve palsy. Initial magnetic resonance imaging (MRI) scans revealed bilateral diffuse subdural fluid collections in all three cases. Follow up MRI scans performed on two patients at 6 months demonstrated partial resolution of the subdural collections but persistent striking meningeal enhancement despite clinical recovery. These findings differ from previous reported cases wherein clinical resolution of postural symptoms was preceded or closely followed by resolution of the MRI changes.