Efficacy of delafloxacin alone and in combination with cefotaxime against cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae.

OBJECTIVE: We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). METHODS: A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. RESULTS: Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. CONCLUSIONS: CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method.

Increase of Diversity of Mumps Virus Genotype G SH Variants Circulating Among a Highly Immunized Population: Spain, 2007-2019.

MuV caused three epidemic waves in Spain since genotype G emerged in 2005, despite high vaccination coverage. SH gene sequencing according to WHO protocols allowed the identification of seven relevant variants and 88 haplotypes. While the originally imported MuVi/Sheffield.GBR/1.05/-variant prevailed during the first two waves, it was subsequently replaced by other variants originated by either local evolution or importation, according to the additional analysis of hypervariable NCRs. The time of emergence of the MRCA of each MuV variant clade was concordant with the data of the earliest sequence. The analysis of Shannon entropy showed an accumulation of variability on six particular positions as the cause of the increase on the number of circulating SH variants. Consequently, SH gene sequencing needs to be complemented with other more variable markers for mumps surveillance immediately after the emergence of a new genotype, but the subsequent emergence of new SH variants turns it unnecessary.

Effectiveness of acellular pertussis vaccine and evolution of pertussis incidence in the community of Madrid from 1998 to 2015.

INTRODUCTION: Pertussis is a communicable disease that primarily affects infants. Vaccination has led to an important reduction in the incidence of the disease, however, resurgence of the disease has been observed. This study aimed to analyze the incidence of pertussis and assess the vaccination effectiveness (VE) of different schedules of acellular pertussis vaccination in the community of Madrid. METHODS: Pertussis cases notified to the Mandatory Disease Reporting System from 1998 to 2015 were analyzed. Five comparison periods were created: 1998-2001 (reference), 2002-2005, 2006-2009, 2010-2012 and 2013-2015. The incidence ratio (IR) between inter-epidemic periods was analyzed using a Poisson regression. VE was calculated using the screening method. Vaccine status data were collected from the vaccine registry. RESULTS: In total, 3855 cases were notified. Inter-epidemic periods were observed every 3-4 years. The incidence increased (IR: 5.99, p < 0.05) in the 2013-2015 period, particularly among infants younger than 1 month (IR: 32.41, p < 0.05). Vaccination data were available in 89% of cases. For those receiving the last dose at ≤6-month VE was 89.9% (95% confidence interval (CI): 87.3-92.0) after one year of follow-up, and 85.5% (95% CI: 82.4-88.1) after 11 years of follow-up. For those receiving the last dose at 18-months VE decreased from 98.8% (95% CI: 98.3-99.1) to 85.1% (95% CI: 81.9-87.7) in the same period, and for those receiving the last dose at 4-year VE decreased from 99.6% (95% CI: 99.3-99.7) to 79.3% (95% CI: 74.6-83.1). CONCLUSIONS: B. pertussis is circulating in our population, as shown by the epidemic peaks and increased incidence of pertussis in recent years. VE increased with the number of doses and decreased with the follow-up period. The effect of this and other vaccination strategies must be monitored to control the disease.

Effectiveness of different vaccine schedules for heptavalent and 13-valent conjugate vaccines against pneumococcal disease in the Community of Madrid.

INTRODUCTION: The heptavalent pneumococcal conjugate vaccine (PCV-7) was added to the childhood routine vaccination program in the Community of Madrid in November of 2006 with 3+1 recommended doses and a catch-up for those under 2years old. In June 2010, PCV-7 was replaced by 13-valent vaccine (PCV-13) with 2+1 recommended doses. In July of 2012, the PCV-13 was removed from the funded program and reintroduced again (2+1 recommended doses) in December 2014. In between, children were vaccinated privately with 3+1 recommended doses of PCV-13. The aim of this study was to evaluate the effectiveness of each vaccination schedule used in the Community of Madrid. METHODS: We included all cases of invasive pneumococcal disease (IPD) reported between 2007 and 2015 to the Notifiable Diseases Surveillance System. Vaccination information was obtained from the Immunization Registry. Vaccine effectiveness (VE) was estimated using the indirect cohort design for cases with serotype information. RESULTS: A total 779 cases were included in the study. Among them 47.6% of the cases were primo-vaccinated with booster, 20% primo-vaccinated, 15.9% incompletely primo-vaccinated and 16.5% not vaccinated. The VE for ≥1 doses of any PCV was 82% (CI 95%: 67.8-89.9%): 91.9% (CI 95%: 76.5-97.2%) for PCV-7 and 77.2% (48.6-89.9%) for PCV-13. VE in those receiving the full 2+1 or 3+1 schedules was 100% for both vaccines. CONCLUSIONS: A high number of vaccine failures were reported in children before they had the opportunity to receive the booster dose, especially due to PCV-13-non-PCV-7 serotypes. VE was higher for PCV-7 compared to PCV-13, except for those that received the complete schedule with booster that achieved 100% of VE, which shows the relevance of the vaccines and complying with all doses scheduled.

Recurrent pneumococcal invasive disease in the region of Madrid during a five-year period.

PURPOSE: The aim of this study was to describe the clinical and microbiological characteristics of recurrent invasive pneumococcal disease (RIPD) cases identified in the Region of Madrid between January 2007 and December 2011. METHODS: Streptococcus pneumoniae serotyping was performed by Pneumotest-Latex and Quellung reaction. Molecular typing was carried out by pulsed-field gel electrophoresis (PFGE). A relapse was defined as any case of RIPD caused by strains with similar PFGE profile. Re-infections were defined by detection of recurrent episodes caused by strains with different PFGE patterns. RESULTS: During the study period, 2,929 S. pneumoniae strains isolated from 2,858 patients with invasive pneumococcal disease (IPD) were studied. In 61 patients (2.1 %), 132 episodes of RIPD were detected (two episodes in 52 patients, three in 8 and four in 1). Twelve patients had relapses, 47 had re-infections and two had re-infections followed by relapses. Common risk factors to developing RIPD were HIV (42.6 %) and haematological malignancies (16.4 %). The most frequent serotypes were 8 (16 episodes) and 19A (15 episodes). Fourteen strains that were resistant to levofloxacin were also resistant to erythromycin. The proportion of strains co-resistant to erythromycin and levofloxacin was significantly higher in relapses (11/29) than in re-infections (3/103). CONCLUSIONS: The occurrence of repeated episodes of IPD in the same patient over the time is not an exceptional issue. Some underlying conditions that may favour these recurrences, mainly immunosuppression, need to be considered in patients having an episode of IPD.

[Outbreak of measles in the population of Spanish origin in North Madrid]. / Brote de 22 casos de sarampión autóctono en la zona norte de Madrid.

After being virtually eradicated in Europe, thousands of cases of measles in the population of Spanish origin have appeared in the last 3 years. We describe the cases diagnosed in the north of Madrid between January and June 2011. A total of 22 cases are reported, 18 of them grouped in 2 outbreaks (2 nurseries). The primary attack rate was 29% in the main outbreak. All cases were in unvaccinated patients (median = 14 months). Genotype D4 was predominant (95%). There was a 45% complication rate and 45% were admitted to hospitals. The Public Health Service recommended isolating cases and vaccinating susceptible contacts in advance. Health Centres established a specific protocol to respond to suspected cases. The Measles vaccination has been brought forward from 15 to 12 months in Madrid. Measles is a re-emerging disease in Europe. The coordinated management between public health and health facilities is essential to limiting outbreaks.

Multidrug-resistant pneumococci (serotype 8) causing invasive disease in HIV+ patients.

From July 2007 to June 2009, all pneumococci causing invasive pneumococcal disease in our hospital were serotyped. Antimicrobial susceptibility was determined by microdilution. Molecular typing was performed by pulsed-field gel electrophoresis and by multilocus sequence typing. Among 251 invasive pneumococci, serotype 8 was the most frequent (13.5%). All serotype 8 strains were susceptible to penicillin; however, 61.8% (21/34) were co-resistant to erythromycin, levofloxacin and tetracycline and identical to the Sweden(15A) -ST63 clone. Serotype 8 was significantly more frequent among human immunodeficiency virus (HIV)-infected patients (36.5%). The high prevalence of this non-conjugate vaccine multiresistant serotype 8 is a cause for concern mainly in HIV-infected patients.

Circulation of mumps virus genotypes in Spain from 1996 to 2007.

Although the WHO recommends the use of genotyping as a tool for epidemiological surveillance for mumps, limited data on mumps virus (MV) genotype circulation that may be used to trace the patterns of virus spread are available. We describe the first complete series of data from Spain. The small hydrophobic region was sequenced from 237 MV-positive samples from several regions of Spain collected between 1996 and 2007. Six different genotypes were identified: A, C, D (D1), G (G1, G2), H (H1, H2), and J. Genotype H1 was predominant during the epidemic that occurred from 1999 to 2003 but was replaced by genotype G1 as the dominant genotype in the epidemic that occurred from 2005 to 2007. The same genotype G1 strain caused concomitant outbreaks in different parts of the world (the United States, Canada, and the United Kingdom). The remaining genotypes (genotypes A, C, D, and J) appeared in sporadic cases or small limited outbreaks. This pattern of circulation seems to reflect continuous viral circulation at the national level, despite the high rates of vaccine coverage.

Phylogenetic analysis of rubella virus strains from an outbreak in Madrid, Spain, from 2004 to 2005.

An outbreak of rubella affected 460 individuals in 2004 and 2005 in the community of Madrid, Spain. Most of the patients were nonvaccinated Latin American immigrants or Spanish males. This study presents the first data on rubella virus genotypes in Spain. Forty selected clinical samples (2 urine, 5 serum, 3 blood, 2 saliva, and 28 pharyngeal exudate samples) from 40 cases were collected. The 739-nucleotide sequence recommended by the World Health Organization obtained from viral RNA in these samples was analyzed by using the MEGA v4.0 software. Seventeen isolates were obtained from 40 clinical samples from the outbreak, including two isolated from congenital rubella syndrome cases. Only viral RNA of genotype 1j was detected in both isolates and clinical specimens. Two variations in amino acids, G253C and T394S, which are involved in neutralization epitopes arose during the outbreak, but apparently there was no positive selection of either of them. The origin of the outbreak remains unknown because of poor virologic surveillance in Latin America and the African countries neighboring Spain. On the other hand, this is the first report of this genotype in Europe. The few published sequences of genotype 1j indicate that it comes from Japan and the Philippines, but there are no epidemiological data supporting this as the origin of the Madrid outbreak.

Incidence trends in pertussis in the Autonomous Region of Madrid, Spain: 1982-2005.

The objective of this study was to describe the incidence (1982-2005) and epidemiologic characteristics of pertussis cases (1998-2005) in the Autonomous Region of Madrid using data drawn from the epidemiologic surveillance network and computerised hospital discharge data. In the 1990s, the trend in the pertussis incidence in the Autonomous Region of Madrid was clearly falling. The typical seasonal pattern of pertussis remained. A peak in incidence were observed in 2000, and another peak, 2.5 times higher, in 2003. They affected all age groups, but children under one year of age were the most frequent cases, followed by the five to nine year-olds. The greatest increase was seen in the age groups from 10 to 14 and from five to nine. Since 2002, the proportion of cases diagnosed serologically has increased. The incidence of hospital discharges among small children exceeded that of reported cases. More than half of the cases with known vaccination status had received at least three doses of vaccine. The upward trend observed since 2002 could be due to improved case detection, availability of serologic techniques, and a rise in the susceptible population aged five to 14 years. The fact that epidemic peaks continue to occur and that there is a seasonality to the disease seems to indicate that despite the vaccination programme the circulation of the bacteria has not been interrupted. The introduction of the acellular vaccine in 2000 does not appear to have played a significant role in the increase in disease incidence.

Late detection of a shigellosis outbreak in a school in Madrid.

Even though shigellosis in Spain is rare, an indigenous outbreak is occasionally detected. We describe an outbreak in a school in Madrid caused by person-to-person transmission of Shigella sonnei. After the detection of Shigella sonnei in a stool sample from a 3 year old girl, an investigation at her school was initiated. Questionnaires were distributed to the parents of 520 pupils attending the school. A case was defined as a school case if it was the first case in a child's household, and as a household case if other members of the household had fallen ill first. We identified 88 cases (60 pupils and 28 of their family members). The attack rate (AR) was 12% in the school and 32% in the families. There was a significant association between higher AR and lower age. The outbreak lasted for two months. The length and the shape of the epidemic curve of the 60 cases in pupils suggests person-to-person transmission. Shigella sonnei isolated from 5 different cases were typed by pulsed field gel electrophoresis (PFGE) and was found to be an identical strain. The prolonged duration of the outbreak was probably due to delayed detection, and stopped as soon as control measures were introduced.

Diagnóstico mediante ELISA de un brote de infección gastrointestinal por Norovirus en una guardería infantil / ELISA Diagnosis of a gastrointestinal norovirus outbreak in a nursery

La incidencia de brotes de gastroenteritis por Norovirus en niños ha sido infravalorada. Esto se ha debido principalmente a la dificultad para disponer de procedimientos diagnósticos adecuados (microscopía electrónica y reacción en cadena de polimerasa de trascripción inversa[RT-PCR]). Los nuevos métodos de enzimoinmuno ensayo (ELISA), capaces de detectar antígenos virales en heces, constituyen una alternativa diagnóstica prometedora. El objetivo de este estudio es describir la aplicación de una técnica de ELISA en la investigación de un brote de gastroenteritis por Norovirus en una guardería. En septiembre de 2003 se notificaron varios casos de gastroenteritis entre niños que acudían a una guardería. El brote afectó a 15 de los 64 niños expuestos. La sintomatología fue vómitos (100%), dolor abdominal (66%), náuseas (40%) y diarrea (40%). La duración del cuadro fue de 3 días (mediana 2 días). Tres pacientes requirieron ingreso hospitalario y todos se recuperaron con tratamiento sintomático. Se estudiaron 3 muestras de heces de 3 pacientes. La presencia de Salmonella sp, Shigella sp y Campylobacter sp se descartó por coprocultivo. La investigación de Norovirus, Rotavirus, Adenovirus y Astrovirus se realizó mediante ELISA específicos (IDEIA NLV, IDEIA Rotavirus, IDEIA Adenovirus e IDEIA Astrovirus; Dako Ltd, Ely UK). En las 3 muestras procesadas se obtuvieron resultados positivos por ELISA para Norovirus y negativos para el resto de los patógenos. La confirmación de resultados para Norovirus se llevó a cabo mediante RT-PCR. La aplicación generalizada de técnicas de ELISA permitirá ayudar a definir en nuestro entorno el papel de los Norovirus como agentes responsables de brotes de gastroenteritis aguda en niños

The incidence of gastrointestinal outbreaks caused by Norovirus in children has been underestimated. This fact is mainly due to the difficulty in the availability of adequate diagnostic procedures (electronic microscopy and Reverse Transcriptase Polymerase Chain Reaction [RTPCR]).The new Enzyme-Linked Immunosorbent Assay (ELISA) methods for the detection of viral antigens in stools represent a promising diagnostic alternative. The objective of this study was to describe the application of an ELISA technique in the investigation of an outbreak by Norovirus in a day care center. In September 2003 several cases of gastroenteritis in children attending a day care center were communicated. The outbreak affected to 15 out of 64 exposed children. The symptomatology was vomits (100%), abdominal pain (66%), nauseas(40%) and diarrhoea (40%). The duration of the symptoms was 3 days (median 2 days). Three patients required hospitalisation and all of them improved with symptomatic treatment. Three faecal samples of three patients were studied. The presence of Salmonella sp, Shigella sp and Campylobacter sp was discarded by coproculture. The investigation of Norovirus, Rotavirus, Adenovirus and Astrovirus was carried out by specific ELISAs (IDEIA NLV, IDEIA Rotavirus, IDEIA Adenovirus e IDEIA Astrovirus; Dako Ltd, Ely UK). In the three processed samples were obtained positive results for Norovirus. These results were confirmed by using RT-PCR. The results for all other pathogens were negative. The wide application of similar ELISA techniques will allow defining the role of Norovirus as agents of gastrointestinal outbreaks among children in our environment

Late detection of a shigellosis outbreak in a school in Madrid.

Even though shigellosis in Spain is rare, an indigenous outbreak is occasionally detected. We describe an outbreak in a school in Madrid caused by person-to-person transmission of Shigella sonnei. After the detection of Shigella sonnei in a stool sample from a 3 year old girl, an investigation at her school was initiated. Questionnaires were distributed to the parents of 520 pupils attending the school. A case was defined as a school case if it was the first case in a child's household, and as a household case if other members of the household had fallen ill first. We identified 88 cases (60 pupils and 28 of their family members). The attack rate (AR) was 12% in the school and 32% in the families. There was a significant association between higher AR and lower age. The outbreak lasted for two months. The length and the shape of the epidemic curve of the 60 cases in pupils suggests person-to-person transmission. Shigella sonnei isolated from 5 different cases were typed by pulsed field gel electrophoresis (PFGE) and was found to be an identical strain. The prolonged duration of the outbreak was probably due to delayed detection, and stopped as soon as control measures were introduced.

New features of rubella in Spain: the evidence of an outbreak.

In most of western Europe the rubella vaccine coverage is high. However, prior to the introduction of the vaccine in Latin America, rubella susceptibility in women of childbearing age was 10-25%. Forty one (93%) countries in Latin America have adopted the rubella vaccine since 2002. The adult immigrant population in Spain constitutes a group of susceptibles. In February 2003, the Madrid Community Measles Elimination Plan detected an increase in rubella notifications in women who had been born in Latin America. A descriptive study was undertaken to characterise the outbreak. A confirmed case was a person with fever or rash and a positive IgM serology, and living in Madrid, between 1 December 2002 and 31 March 2003. The secondary attack rate (SAR) per household was calculated. A total of 19 cases of rubella were identified, 15 were confirmed and 4 were probable cases. Fourteen (73.7%) cases were women at childbearing age. The mean age was 25.1 years. One pregnancy was diagnosed with a voluntary termination. Eleven (57.9%) cases were from Ecuador. The mean time of residence in Spain was 41 months. None of the cases or the 54 (78.3%) household contacts had been vaccinated against rubella. The SAR was 9.1%. This study showed the spread of rubella in the susceptible Latin American Community that is resident in Madrid. The interventions proposed were a vaccination programme towards immigrants, a health education campaign to prevent congenital rubella, and a health professional training programme case management.

Is there a change in cytomegalovirus seroepidemiology in Spain?

The aim of this paper is to compare the seroprevalence of cytomegalovirus (CMV) in women in the Autonomous Region of Madrid (ARM) obtained in two different years (1993 and 1999), according to age and seroprevalence of a virus transmitted by the faecal-oral route (hepatitis A virus, HAV) and another virus of respiratory transmission (varicella zoster virus, VZV). A total of 1813 serum samples were studied, taken from females aged 2-40 in two different serosurveys which were representative of the general population in the ARM. Of these, 933 were taken in 1993, and 880 in 1999. In each survey the samples were distributed over six groups, according to age group (2-5, 6-10, 11-15, 16-20, 21-30 and 31-40 years). CMV- and VZV-specific IgG was tested by indirect ELISA (Dade-Behring, Germany); and HAV-IgG by ImX (Abbott, USA) in the 1993 samples, or by Vidas (BioMérieux, France) in the case of those taken in 1999. A significant age-related rise in CMV seroprevalence was observed in both serosurveys. The seroprevalence obtained was lower in all age groups in 1999 than in 1993. The differences were statistically significant in two age groups: 6-10 years old (43.7 vs. 56.7%) and 31-40 years old (79.1 vs. 90.3%). In the younger age groups concurrent seroprevalence of CMV and VZV was significant lower in 1999. In older age groups a significant decrease in concurrent seroprevalence of both CMV and HAV was also seen. Agreement between serological results for CMV-HAV, CMV-VZV and HAV-VVZ during the two time periods and in every age group was poor or fair (kappa index < or = 0.2 or between 0.21 and 0.4) in all age groups. To conclude, a change in CMV epidemiology seems to be taking place in Madrid. The increase in the proportion of CMV seronegative women of childbearing age may have some impact on the incidence of congenital diseases related to vertical transmission of CMV. Apparently, such a change, among children, could be related to a lower close contact transmission rate (as in VZV), and among adults to improvements in standards of public health (as in HAV). However, due to the poor or fair agreement between serological results for CMV-HAV, CMV-VZV and HAV-VVZ, other independent factors may affect the fall in CMV seroprevalence.

New features of rubella in Spain: the evidence of an outbreak.

In most of western Europe the rubella vaccine coverage is high. However, prior to the introduction of the vaccine in Latin America, rubella susceptibility in women of childbearing age was 10-25%. Forty one (93%) countries in Latin America have adopted the rubella vaccine since 2002. The adult immigrant population in Spain constitutes a group of susceptibles. In February 2003, the Madrid Community Measles Elimination Plan detected an increase in rubella notifications in women who had been born in Latin America. A descriptive study was undertaken to characterise the outbreak. A confirmed case was a person with fever or rash and a positive IgM serology, and living in Madrid, between 1 December 2002 and 31 March 2003. The secondary attack rate (SAR) per household was calculated. A total of 19 cases of rubella were identified, 15 were confirmed and 4 were probable cases. Fourteen (73.7%) cases were women at childbearing age. The mean age was 25.1 years. One pregnancy was diagnosed with a voluntary termination. Eleven (57.9%) cases were from Ecuador. The mean time of residence in Spain was 41 months. None of the cases or the 54 (78.3%) household contacts had been vaccinated against rubella. The SAR was 9.1%. This study showed the spread of rubella in the susceptible Latin American Community that is resident in Madrid. The interventions proposed were a vaccination programme towards immigrants, a health education campaign to prevent congenital rubella, and a health professional training programme case management.

Prevalence of CagA and VacA antibodies in children with Helicobacter pylori-associated peptic ulcer compared to prevalence in pediatric patients with active or nonactive chronic gastritis.

VacA and CagA serological responses were detected in pediatric patients: 44 and 56%, respectively, in peptic ulcer (PU) patients, 33.3 and 44.4% in active chronic gastritis (ACG) patients, and 23.2 and 39.2% in non-ACG patients. Higher seroprevalence to CagA+VacA and to CagA+VacA+35-kDa antigen was found among PU patients. However, a low level of sensitivity and specificity was found for indirect detection of PU patients.

[Tension pneumoperitoneum as complication in a case of perioperative barotrauma]. / Neumoperitoneo a tensión como complicación en un caso de barotrauma peroperatorio.

Tension pneumoperitoneum is rare complication that causes severe changes in respiratory and cardiocirculatory function. We report the case of an 84 year old woman who developed tension pneumoperitoneum soon after cholecystectomy by subcostal laparotomy. Tension pneumoperitoneum presented with barotrauma, bilateral pneumothorax, extensive subcutaneous and pneumomediastinum and was accompanied by severe worsening of hemodynamic variables and gas exchange. After confirming the diagnosis by emergency CT scan, the first therapeutic action was decompression of the peritoneal. This fast, simple maneuver was followed by rapid hemodynamic and respiratory improvement. Tension pneumoperitoneum similar to the case we report has been described as a complication of mechanical ventilation and barotrauma; however, the possibility that the clinical picture might be caused by perforation of a hollow viscera has given rise to a variety of suggested therapeutic alternatives, including exploratory laparotomy, which has sometimes later proven to have been unnecessary. In the light of the case we report and the literature, we suggest a therapeutic sequence starting with emergency abdominal decompression and to fulfill two objectives: a) to remove the threat to life, and b) to limit the practice of emergency exploratory laparotomy to cases in which that technique is truly indicated.